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  1. Genetic screening

    PubMed Central

    Andermann, Anne; Blancquaert, Ingeborg

    2010-01-01

    Abstract OBJECTIVE To provide a primer for primary care professionals who are increasingly called upon to discuss the growing number of genetic screening services available and to help patients make informed decisions about whether to participate in genetic screening, how to interpret results, and which interventions are most appropriate. QUALITY OF EVIDENCE As part of a larger research program, a wide literature relating to genetic screening was reviewed. PubMed and Internet searches were conducted using broad search terms. Effort was also made to identify the gray literature. MAIN MESSAGE Genetic screening is a type of public health program that is systematically offered to a specified population of asymptomatic individuals with the aim of providing those identified as high risk with prevention, early treatment, or reproductive options. Ensuring an added benefit from screening, as compared with standard clinical care, and preventing unintended harms, such as undue anxiety or stigmatization, depends on the design and implementation of screening programs, including the recruitment methods, education and counseling provided, timing of screening, predictive value of tests, interventions available, and presence of oversight mechanisms and safeguards. There is therefore growing apprehension that economic interests might lead to a market-driven approach to introducing and expanding screening before program effectiveness, acceptability, and feasibility have been demonstrated. As with any medical intervention, there is a moral imperative for genetic screening to do more good than harm, not only from the perspective of individuals and families, but also for the target population and society as a whole. CONCLUSION Primary care professionals have an important role to play in helping their patients navigate the rapidly changing terrain of genetic screening services by informing them about the benefits and risks of new genetic and genomic technologies and empowering them to

  2. Genetic Screening

    PubMed Central

    Burke, Wylie; Tarini, Beth; Press, Nancy A.; Evans, James P.

    2011-01-01

    Current approaches to genetic screening include newborn screening to identify infants who would benefit from early treatment, reproductive genetic screening to assist reproductive decision making, and family history assessment to identify individuals who would benefit from additional prevention measures. Although the traditional goal of screening is to identify early disease or risk in order to implement preventive therapy, genetic screening has always included an atypical element—information relevant to reproductive decisions. New technologies offer increasingly comprehensive identification of genetic conditions and susceptibilities. Tests based on these technologies are generating a different approach to screening that seeks to inform individuals about all of their genetic traits and susceptibilities for purposes that incorporate rapid diagnosis, family planning, and expediting of research, as well as the traditional screening goal of improving prevention. Use of these tests in population screening will increase the challenges already encountered in genetic screening programs, including false-positive and ambiguous test results, overdiagnosis, and incidental findings. Whether this approach is desirable requires further empiric research, but it also requires careful deliberation on the part of all concerned, including genomic researchers, clinicians, public health officials, health care payers, and especially those who will be the recipients of this novel screening approach. PMID:21709145

  3. Pathways to genetic screening: Patient knowledges, patient practices. Annual report

    SciTech Connect

    1994-12-31

    This study is design to assess the impacts of the integration of genetic knowledge in to the life of high-risk family members. The social and cultural barriers and bridges that incorporation of genetic information will have on these families as well as how they use this genetic information to increase reproductive options and improve the quality of family life are a major focus of this work.

  4. Preimplantation genetic screening.

    PubMed

    Harper, Joyce C

    2017-01-01

    Preimplantation genetic diagnosis was first successfully performed in 1989 as an alternative to prenatal diagnosis for couples at risk of transmitting a genetic or chromosomal abnormality, such as cystic fibrosis, to their child. From embryos generated in vitro, biopsied cells are genetically tested. From the mid-1990s, this technology has been employed as an embryo selection tool for patients undergoing in vitro fertilisation, screening as many chromosomes as possible, in the hope that selecting chromosomally normal embryos will lead to higher implantation and decreased miscarriage rates. This procedure, preimplantation genetic screening, was initially performed using fluorescent in situ hybridisation, but 11 randomised controlled trials of screening using this technique showed no improvement in in vitro fertilisation delivery rates. Progress in genetic testing has led to the introduction of array comparative genomic hybridisation, quantitative polymerase chain reaction, and next generation sequencing for preimplantation genetic screening, and three small randomised controlled trials of preimplantation genetic screening using these new techniques indicate a modest benefit. Other trials are still in progress but, regardless of their results, preimplantation genetic screening is now being offered globally. In the near future, it is likely that sequencing will be used to screen the full genetic code of the embryo.

  5. Assessment of an Interactive Computer-Based Patient Prenatal Genetic Screening and Testing Education Tool

    ERIC Educational Resources Information Center

    Griffith, Jennifer M.; Sorenson, James R.; Bowling, J. Michael; Jennings-Grant, Tracey

    2005-01-01

    The Enhancing Patient Prenatal Education study tested the feasibility and educational impact of an interactive program for patient prenatal genetic screening and testing education. Patients at two private practices and one public health clinic participated (N = 207). The program collected knowledge and measures of anxiety before and after use of…

  6. Genetic screening of Greek patients with Huntington’s disease phenocopies identifies an SCA8 expansion.

    PubMed

    Koutsis, G; Karadima, G; Pandraud, A; Sweeney, M G; Paudel, R; Houlden, H; Wood, N W; Panas, M

    2012-09-01

    Huntington’s disease (HD) is an autosomal dominant disorder characterized by a triad of chorea, psychiatric disturbance and cognitive decline. Around 1% of patients with HD-like symptoms lack the causative HD expansion and are considered HD phenocopies. Genetic diseases that can present as HD phenocopies include HD-like syndromes such as HDL1, HDL2 and HDL4 (SCA17), some spinocerebellar ataxias (SCAs) and dentatorubral-pallidoluysian atrophy (DRPLA). In this study we screened a cohort of 21 Greek patients with HD phenocopy syndromes formutations causing HDL2, SCA17, SCA1, SCA2, SCA3,SCA8, SCA12 and DRPLA. Fifteen patients (71%) had a positive family history. We identified one patient (4.8% of the total cohort) with an expansion of 81 combined CTA/CTG repeats at the SCA8 locus. This falls within what is believed to be the high-penetrance allele range. In addition to the classic HD triad, the patient had features of dystonia and oculomotor apraxia. There were no cases of HDL2, SCA17, SCA1, SCA2, SCA3, SCA12 or DRPLA. Given the controversy surrounding the SCA8 expansion, the present finding may be incidental. However, if pathogenic, it broadens the phenotype that may be associated with SCA8 expansions. The absence of any other mutations in our cohort is not surprising, given the low probability of reaching a genetic diagnosis in HD phenocopy patients.

  7. Genetic screening for deafness.

    PubMed

    Smith, Richard J H; Hone, Stephen

    2003-04-01

    Genetic testing for deafness has become a reality. It has changed the paradigm for evaluating deaf and hard-of-hearing persons and will be used by physicians for diagnostic purposes and as a basis for treatment and management options. Although mutation screening is currently available for only a limited number of genes, in these specific instances, diagnosis, carrier detection, and reproductive risk counseling can be provided. In the coming years there will be an expansion of the role of genetic testing and counseling will not be limited to reproductive issues. Treatment and management decisions will be made based on specific genetic diagnoses. Although genetic testing may be a confusing service for the practicing otolaryngologist, it is an important part of medical care. New discoveries and technologies will expand and increase the complexity of genetic testing options and it will become the responsibility of otolaryngologists to familiarize themselves with current discoveries and accepted protocols for genetic testing.

  8. A genetic screen of the mutations in the Korean patients with early-onset Alzheimer's disease.

    PubMed

    An, Seong Soo; Park, Sun Ah; Bagyinszky, Eva; Bae, Sun Oh; Kim, Yoon-Jeong; Im, Ji Young; Park, Kyung Won; Park, Kee Hyung; Kim, Eun-Joo; Jeong, Jee Hyang; Kim, Jong Hun; Han, Hyun Jeong; Choi, Seong Hye; Kim, SangYun

    2016-01-01

    Early-onset Alzheimer's disease (EOAD) has distinct clinical characteristics in comparison to late-onset Alzheimer's disease (LOAD). The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS) study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer's disease (AD) mutations in the consecutive EOAD subjects from the CREDOS study from April 2012 to February 2014. We checked the sequence of APP (exons 16-17), PSEN1 (exons 3-12), and PSEN2 (exons 3-12) genes. We identified different causative or probable pathogenic AD mutations, PSEN1 T116I, PSEN1 L226F, and PSEN2 V214L, employing 24 EOAD subjects with a family history and 80 without a family history of dementia. PSEN1 T116I case demonstrated autosomal dominant trait of inheritance, with at least 11 affected individuals over 2 generations. However, there was no family history of dementia within first-degree relation in PSEN1 L226F and PSEN2 V214L cases. Approximately, 55.7% of the EOAD subjects had APOE ε4 allele, while none of the mutation-carrying subjects had the allele. The frequency of genetic mutation in this study is lower compared to the studies from other countries. The study design that was based on nationwide cohort, which minimizes selection bias, is thought to be one of the contributors to the lower frequency of genetic mutation. However, the possibility of the greater likeliness of earlier onset of sporadic AD in Korea cannot be excluded. We

  9. [Cost-effectiveness analysis of a genetic screening program in the close relatives of Spanish patients with familial hypercholesterolemia].

    PubMed

    Oliva, Juan; López-Bastida, Julio; Moreno, Santiago G; Mata, Pedro; Alonso, Rodrigo

    2009-01-01

    The aim was to assess the cost-effectiveness of a genetic screening program for first-degree relatives of patients with familial hypercholesterolemia (FH), followed by treatment when necessary, compared with the alternative of no screening. The cost-effectiveness analysis modeled the effect of statin treatment on individuals who were diagnosed with FH after genetic screening. The impact of uncertainty was evaluated using univariate probabilistic sensitivity analysis. The alternate strategy considered was no screening. In the cost-effectiveness analysis, the number of life-years gained (LYG) was regarded as the health outcome and the costs of screening, statin treatment, specialist consultations and hospital visits were all included. In addition, the expected value of perfect information was calculated as part of the sensitivity analysis. In the base case, the incremental cost of the screening program for close relatives was 3423 euros per LYG. Although the sensitivity analysis gave a range of results, the conclusions were not affected by changes in the parameters considered. The screening program was found to be better than the alternative considered at a probability level of 95% if the acceptable level of health-care costs was at least 7400 euros per LYG. This analysis indicates that a genetic screening program, supplemented by treatment, for the close relatives of individuals with FH is preferable to the alternative of no screening in terms of incremental cost-effectiveness.

  10. Genetic Screening for Employment Purposes.

    ERIC Educational Resources Information Center

    Olian, Judy D.

    1984-01-01

    Discusses genetic screening in the employment context, which involves identification of individuals hypersusceptible to toxins in the work environment. Examines the status of genetic screening devices against standard testing and legal criteria. (LLL)

  11. Quick genetic screening using targeted next-generation sequencing in patients with tuberous sclerosis.

    PubMed

    Liu, Qing; Huang, Yan; Zhang, Mingrong; Wang, Lian Qing; Guo, Xia Nan; Si, Nuo; Qi, Zhan; Zhou, Xiang Qin; Cui, Li-ying

    2015-04-01

    Tuberous sclerosis complex is an autosomal dominant disorder characterized by hamartomas in multiple organ systems. Mutations in the 2 large genes TSC1 and TSC2 have been demonstrated to be associated with tuberous sclerosis complex by various mutation screening methods. Targeted next-generation sequencing for genetic analysis is performed in the current study and is proved to be less cost, labor, and time consuming compared with Sanger sequencing. Two de novo and 1 recurrent TSC2 mutation in patients with tuberous sclerosis complex were revealed. Clinical details of patients were described and the underlying mechanism of the 2 novel TSC2 mutations, c.245G>A(p.W82X) and c.5405_5408dupACTT(p.P1803Lfs*25), were discussed. These results added to variability of TSC mutation spectrum and suggest that targeted next-generation sequencing could be the primary choice over Sanger sequencing in future tuberous sclerosis complex genetic counseling. © The Author(s) 2014.

  12. Genetic Screening and Analysis of LKB1 Gene in Chinese Patients with Peutz-Jeghers Syndrome

    PubMed Central

    Chen, Chunyan; Zhang, Xiaomei; Wang, Deqiang; Wang, Fangyu; Pan, Jian; Wang, Zhenkai; Liu, Chang; Wu, Lin; Lu, Heng; Li, Nan; Wei, Juan; Shi, Hui; Wan, Haijun; Zhu, Ming; Chen, Senqing; Zhou, Yun; Zhou, Xin; Yang, Liu; Liu, Jiong

    2016-01-01

    Background Peutz-Jeghers syndrome (PJS) is an autosomal dominant genetic disease. It severely decreases patient quality of life and leads elevated cancer risk. Germline mutation of LKB1 is the leading cause of familial PJS. Material/Methods To characterize the germline mutation of LKB1 gene in Chinese familial and sporadic PJS patients, 14 PJS families, 5 sporadic PJS patients, and 250 healthy adults were collected and genomic DNAs of peripheral blood were extracted. Mutation screenings of LKB1 were performed using MLPA (multiplex ligation-dependent probe amplification), PCR, direct sequencing, and PCR-DHPLC (denaturing high-performance liquid chromatography). Results A total of 12 kinds of germline mutations were found in 9 familial PJS patients, most of which were point mutations (7/12); 4 large deletions of LKB1 were also observed. Of the 12 mutations, 7 were pathogenic (2 were de novo), 4 were just polymorphisms, and 1 was indefinitely pathogenic. No pathogenic mutation in exons of the LKB1 gene was detected in the 5 sporadic PJS patients. The mutation detection rate for the LKB1 gene was 85.7% in our Chinese familial PJS and 63.2% in all Chinese PJS patients. Eight familial PJS patients were identified with pathogenic germline mutations in 14 unrelated families (57.1%). Further methylation detection and analysis showed promoter methylation in carcinomatous polyps. Conclusions LKB1 gene germline mutation with pathogenic effect is a common cause of familial PJS in Chinese patients; however, it is not the only molecular pathogen of PJS. Methylation in the LKB1 gene promoter region may cause carcinomatous change in intestinal polyps. PMID:27721366

  13. Patients' ratings of genetic conditions validate a taxonomy to simplify decisions about preconception carrier screening via genome sequencing.

    PubMed

    Leo, Michael C; McMullen, Carmit; Wilfond, Benjamin S; Lynch, Frances L; Reiss, Jacob A; Gilmore, Marian J; Himes, Patricia; Kauffman, Tia L; Davis, James V; Jarvik, Gail P; Berg, Jonathan S; Harding, Cary; Kennedy, Kathleen A; Simpson, Dana Kostiner; Quigley, Denise I; Richards, C Sue; Rope, Alan F; Goddard, Katrina A B

    2016-03-01

    Advances in genome sequencing and gene discovery have created opportunities to efficiently assess more genetic conditions than ever before. Given the large number of conditions that can be screened, the implementation of expanded carrier screening using genome sequencing will require practical methods of simplifying decisions about the conditions for which patients want to be screened. One method to simplify decision making is to generate a taxonomy based on expert judgment. However, expert perceptions of condition attributes used to classify these conditions may differ from those used by patients. To understand whether expert and patient perceptions differ, we asked women who had received preconception genetic carrier screening in the last 3 years to fill out a survey to rate the attributes (predictability, controllability, visibility, and severity) of several autosomal recessive or X-linked genetic conditions. These conditions were classified into one of five taxonomy categories developed by subject experts (significantly shortened lifespan, serious medical problems, mild medical problems, unpredictable medical outcomes, and adult-onset conditions). A total of 193 women provided 739 usable ratings across 20 conditions. The mean ratings and correlations demonstrated that participants made distinctions across both attributes and categories. Aggregated mean attribute ratings across categories demonstrated logical consistency between the key features of each attribute and category, although participants perceived little difference between the mild and serious categories. This study provides empirical evidence for the validity of our proposed taxonomy, which will simplify patient decisions for results they would like to receive from preconception carrier screening via genome sequencing.

  14. [Clinical and genetic findings in patients with biotinidase deficiency detected through newborn screening or selective screening for hearing loss or inherited metabolic disease].

    PubMed

    Couce, María Luz; Pérez-Cerdá, Celia; García Silva, María Teresa; García Cazorla, Angels; Martín-Hernández, Elena; Castiñeiras, Daisy; Pineda, Merçè; Navarrete, Rosa; Campistol, Jaume; Fraga, José María; Pérez, Belén; Ugarte, Magdalena

    2011-10-22

    To evaluate clinical, biochemical and genetic findings of two series of patients with biotinidase deficiency. Fifteen cases detected through newborn screening and six through selective screening for hearing loss or metabolic disease. No patient detected by neonatal screening had symptoms and only one case with partial biotinidase activity developed myoclonic seizures that resolved with biotin. More common mutations found among this group were p.D444H and the double mutation [p.D444H;p.A171T]. However, neurological and hearing manifestations predominated among the six symptomatic cases and mutations p.L32fs, p.G34fs, p.T401I, p.D444H, p.T532M and the novel one p.L466fs were identified. Patients with profound biotinidase deficiency and/or clinical signs were treated with pharmacological doses of biotin (10-30mg daily). Biotinidase deficiency must be included in the newborn screening programmes in order to begin early treatment even in partial forms. Different mutations found in both series of patients suggest that routine genetic procedure of the BTD gene by direct sequencing might be useful to assign patients to the partial or profound form of the disease. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  15. Pathways to genetic screening: Patient knowledges, Patient practices. Technical report of research progress

    SciTech Connect

    Not Available

    1994-08-29

    This study is designed to clarify the integration of genetic knowledge into the lived experience of high-risk family members. A major focus is elucidation of the social and cultural barriers and bridges to the use of genetic information to increase reproductive options and improve the quality of family life. They study focuses on families at risk for cystic fibrosis and sickle cell disease. These two disease groups were selected because they are among the most common potentially lethal genetic diseases and because while each has a similar pattern of inheritance and raises similarly serious bio-medical challenges and issues of information management, they primarily affect different racial and ethno-cultural groups permitting a naturally occurring experiment. In the variable penetration and meaning of genetic medicine in two populations. We have conducted intensive interviews with more than 300 individuals in approximately 88 families. We have attempted to balance the effort equally between the two groups, but have found we are able to penetrate the family systems of the cystic fibrosis families more easily than the sickle cell families.

  16. The measurement of patient attitudes regarding prenatal and preconception genetic carrier screening and translational behavioral medicine: an integrative review.

    PubMed

    Shiroff, Jennifer J; Gregoski, Mathew J

    2016-08-29

    Measurement of recessive carrier screening attitudes related to conception and pregnancy is necessary to determine current acceptance, and whether behavioral intervention strategies are needed in clinical practice. To evaluate quantitative survey instruments to measure patient attitudes regarding genetic carrier testing prior to conception and pregnancy databases examining patient attitudes regarding genetic screening prior to conception and pregnancy from 2003-2013 were searched yielding 344 articles; eight studies with eight instruments met criteria for inclusion. Data abstraction on theoretical framework, subjects, instrument description, scoring, method of measurement, reliability, validity, feasibility, level of evidence, and outcomes was completed. Reliability information was provided in five studies with an internal consistency of Cronbach's α >0.70. Information pertaining to validity was presented in three studies and included construct validity via factor analysis. Despite limited psychometric information, these questionnaires are self-administered and can be briefly completed, making them a feasible method of evaluation.

  17. Genetic screening: marvel or menace?

    PubMed

    Rowley, P T

    1984-07-13

    Genetic screening is a systematic search in the population for persons of certain genotypes. The usual purpose is to detect persons who themselves or whose offspring are at risk for genetic diseases or genetically determined susceptibilities to environmental agents. Is genetic screening a marvel about to free us from the scourge of genetic disease or a menace about to invade our privacy and determine who may reproduce? There are three different types of genetic screening. Newborn screening identifies serious genetic disease at birth, permitting prompt treatment to prevent mental and physical retardation. Fetal screening and prenatal diagnosis identify genetic disease in the fetus permitting selective termination of pregnancy and the opportunity to have children free of defects detectable in utero. Carrier screening identifies individuals heterozygous for a gene for a serious recessive disease who may be at risk for affected offspring. The challenge to society is to provide (by way of cost-effective programs) expert services, including genetic counseling and follow-up, to all who may benefit, to ensure confidentiality and freedom of choice, and to avoid misunderstanding and stigmatization. It is recommended that the objective of screening programs should be to maximize the options available to families at risk rather than to reduce the incidence of genetic diseases. Whenever possible, the providers of these services should be the providers of primary health care. Urgently needed are a greater awareness of avoidable genetic diseases on the part of primary care providers and efforts to familiarize the public with the basic concepts of human genetics through the public school system.

  18. Phenylketonuria Genetic Screening Simulation

    ERIC Educational Resources Information Center

    Erickson, Patti

    2012-01-01

    After agreeing to host over 200 students on a daylong genetics field trip, the author needed an easy-to-prepare genetics experiment to accompany the DNA-necklace and gel-electrophoresis activities already planned. One of the student's mothers is a pediatric physician at the local hospital, and she suggested exploring genetic-disease screening…

  19. Phenylketonuria Genetic Screening Simulation

    ERIC Educational Resources Information Center

    Erickson, Patti

    2012-01-01

    After agreeing to host over 200 students on a daylong genetics field trip, the author needed an easy-to-prepare genetics experiment to accompany the DNA-necklace and gel-electrophoresis activities already planned. One of the student's mothers is a pediatric physician at the local hospital, and she suggested exploring genetic-disease screening…

  20. Judaism, genetic screening and genetic therapy.

    PubMed

    Rosner, F

    1998-01-01

    Genetic screening, gene therapy and other applications of genetic engineering are permissible in Judaism when used for the treatment, cure, or prevention of disease. Such genetic manipulation is not considered to be a violation of God's natural law, but a legitimate implementation of the biblical mandate to heal. If Tay-Sachs disease, diabetes, hemophilia, cystic fibrosis, Huntington's disease or other genetic diseases can be cured or prevented by "gene surgery," then it is certainly permitted in Jewish law. Genetic premarital screening is encouraged in Judaism for the purpose of discouraging at-risk marriages for a fatal illness such as Tay-Sachs disease. Neonatal screening for treatable conditions such as phenylketonuria is certainly desirable and perhaps required in Jewish law. Preimplantation screening and the implantation of only "healthy" zygotes into the mother's womb to prevent the birth of an affected child are probably sanctioned in Jewish law. Whether or not these assisted reproduction techniques may be used to choose the sex of one's offspring, to prevent the birth of a child with a sex-linked disease such as hemophilia, has not yet been ruled on by modern rabbinic decisions. Prenatal screening with the specific intent of aborting an affected fetus is not allowed according to most rabbinic authorities, although a minority view permits it "for great need." Not to have children if both parents are carriers of genetic diseases such as Tay-Sachs is not a Jewish option. Preimplantation screening is preferable. All screening test results must remain confidential. Judaism does not permit the alteration or manipulation of physical traits and characteristics such as height, eye and hair color, facial features and the like, when such change provides no useful benefit to mankind. On the other hand, it is permissible to clone organisms and microorganisms to facilitate the production of insulin, growth hormone, and other agents intended to benefit mankind and to

  1. Genetic Counselor Practices Involving Pediatric Patients with FAP: an Investigation of their Self-Reported Strategies for Genetic Testing and Hepatoblastoma Screening.

    PubMed

    Lawson, Caitlin E; Attard, Thomas M; Dai, Hongying; Septer, Seth

    2017-06-01

    Familial adenomatous polyposis (FAP) is a cancer predisposition syndrome that causes early-onset polyposis and is associated with an increased risk for hepatoblastoma. There is currently a lack of consensus on when to order APC (adenomatous polyposis coli) gene testing or implement surveillance for hepatoblastoma. An online questionnaire was completed by 62 genetic counselors to capture their current practices regarding these questions. Extracolonic findings associated with FAP that were most likely to prompt APC testing in an otherwise asymptomatic 10 year-old child with a negative family history were multiple desmoid tumors, congenital hypertrophy of the retinal pigment epithelium (CHRPE), jaw osteomas, and hepatoblastoma. For hepatoblastoma screening, the majority did recommend this in children less than age five years with known APC mutations. An interval of every 3-6 months was most commonly suggested; however, responses extended to screening on a less than annual basis. These results highlight the need for further investigation into why some genetic counselors do not recommend APC testing in young at-risk children and what factors influence views about the ideal age and indication for APC testing. Studies of these issues would help to define the best clinical practice model for genetic testing and hepatoblastoma screening in pediatric patients with FAP.

  2. National Newborn Screening and Genetics Resource Center

    MedlinePlus

    ... GENERAL INFORMATION Conditions Screened by US Programs General Resources Genetics Birth Defects Hearing Screening FOR PROFESSIONALS ACT Sheets(ACMG) General Resources Newborn Screening Genetics Birth Defects FOR FAMILIES FAQs ...

  3. Analyses of Genetic and Clinical Parameters for Screening Patients With Inherited Thrombocytopenia with Small or Normal-Sized Platelets.

    PubMed

    Ouchi-Uchiyama, Meri; Sasahara, Yoji; Kikuchi, Atsuo; Goi, Kumiko; Nakane, Takaya; Ikeno, Mitsuru; Noguchi, Yasushi; Uike, Naokuni; Miyajima, Yuji; Matsubara, Kousaku; Koh, Katsuyoshi; Sugita, Kanji; Imaizumi, Masue; Kure, Shigeo

    2015-12-01

    Childhood thrombocytopenias include immune thrombocytopenic purpura (ITP) and inherited thrombocytopenia; the former is caused by autoantibodies to platelets, whereas the latter can be distinguished by platelet size and underlying genetic mutations. Due to limited methods for the definite diagnosis of ITP, genetic and clinical parameters are required for diagnosing inherited thrombocytopenias with small or normal-sized platelets. In total, 32 Japanese patients with thrombocytopenia with small or normal-sized platelets from 29 families were enrolled. All the patients were under 20 years of age, with family histories of early-onset thrombocytopenia and/or poor response to conventional therapies for ITP. Genotypes and clinical parameters were retrospectively evaluated according to the disease type. Twelve cases of inherited thrombocytopenia were observed. We identified chromosomal deletions within the WASP gene in two patients with Wiskott-Aldrich syndrome; a missense mutation in a patient with X-linked thrombocytopenia; and mutations in the RUNX1 gene of five patients with familial platelet disorder with propensity to acute myelogenous leukemia, and in the ANKRD26 gene of four patients with autosomal dominant thrombocytopenia-2. All 12 carried germline mutations, three of which were de novo. Furthermore, we observed significantly elevated serum thrombopoietin (TPO) levels and dysplasia of megakaryocytes in patients carrying the RUNX1 and ANKRD26 mutations. Genetic analyses and detection of TPO levels and dysmegakaryopoiesis were clinically useful for screening patients with inherited thrombocytopenias, irrespective of the family history. We hypothesize that the WASP, RUNX1, and ANKRD26 genes are important for normal TPO signaling and the network underlying thrombopoiesis. © 2015 Wiley Periodicals, Inc.

  4. Prenatal Genetic Screening Tests

    MedlinePlus

    ... Resources & Publications Committee Opinions Practice Bulletins Patient Education Green Journal Clinical Updates Practice Management Coding Health Info Technology Professional Liability Managing Your Practice Patient Safety & Quality ...

  5. Preimplantation genetic screening: who benefits?

    PubMed

    Kang, Hey-Joo; Melnick, Alexis P; Stewart, Joshua D; Xu, Kangpu; Rosenwaks, Zev

    2016-09-01

    To compare IVF outcomes between women undergoing frozen transfers of blastocysts verified as euploid by preimplantation genetic screening (PGS) with patients undergoing fresh nonbiopsied blastocyst transfers. Retrospective cohort study. Academic medical center. All patients undergoing IVF-PGS cycles between January 2010 and November 2014 were included (n = 274). Patients were compared with a control group consisting of all fresh blastocyst transfers that occurred during the same period (n = 863). Patients underwent IVF-PGS with 24-chromosome screening. Patients with euploid embryos had transfer of one to two embryos in a subsequent frozen ET cycle. Implantation, clinical intrauterine gestation (CIG), miscarriage, biochemical pregnancy (BC), and live birth (LB) rates were compared. Odds ratios (ORs) were estimated for outcomes in women undergoing PGS versus controls. Among patients ≤37 years old, there were no differences in CIG and LB rates for single (adjusted ORs [aORs], 1.20 [95 %confidence interval {CI}, 0.66-2.21]; 1.21 [95% CI, 0.66-2.2]) and double ETs (aORs, 1.09 [95% CI, 0.54-2.18]; 0.87 [95% CI, 0.44-1.7]). BC and miscarriage rates were also similar. For patients >37 years old, CIG and LB rates were increased for single (aORs, 3.86 [95% CI, 1.25-11.9]; 8.2 [95% CI, 2.28-29.5]) and double ETs (aORs, 9.91 [95% CI, 2.0-49.6]; 8.67 [95% CI, 2.08-36.2]) with no difference in BC and miscarriage rates. A per-retrieval analysis of the >37 group failed to demonstrate any difference in CIG or LB rates. Among patients ≤37, IVF-PGS does not improve CIG, LB, and miscarriage rates. IVF-PGS in women >37 improved CIG and LB rates. However, per cycle, the PGS advantage in this age group does not persist. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  6. Optimal screening for genetic diseases.

    PubMed

    Nævdal, Eric

    2014-12-01

    Screening for genetic diseases is performed in many regions and/or ethnic groups where there is a high prevalence of possibly malign genes. The propagation of such genes can be considered a dynamic externality. Given that many of these diseases are untreatable and give rise to truly tragic outcomes, they are a source of societal concern, and the screening process should perhaps be regulated. This paper incorporates a standard model of genetic propagation into an economic model of dynamic management to derive cost benefit rules for optimal screening. The highly non-linear nature of genetic dynamics gives rise to perhaps surprising results that include discontinuous controls and threshold effects. One insight is that any screening program that is in place for any amount of time should screen all individuals in a target population. The incorporation of genetic models may prove to be useful to several emerging fields in economics such as genoeconomics, neuroeconomics and paleoeconomics. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Genetic Screening of Mutations Associated with Fabry Disease in a Nationwide Cohort of Juvenile Idiopathic Arthritis Patients

    PubMed Central

    Gonçalves, Maria J.; Mourão, Ana F.; Martinho, António; Simões, Olívia; Melo-Gomes, José; Salgado, Manuel; Estanqueiro, Paula; Ribeiro, Célia; Brito, Iva; Fonseca, João E.; Canhão, Helena

    2017-01-01

    Fabry’s disease (FD) is a lysosomal storage disorder associated with an alpha-galactosidase A deficiency. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients with established diagnosis is unknown, but as musculoskeletal pain may be an important complaint at presentation, misdiagnosed cases are anticipated. With this study, we aim to calculate the frequency of FD-associated mutations in a cohort of JIA patients. Children with JIA from a national cohort were selected. Clinical and laboratorial information was recorded in the Portuguese rheumatic diseases register (http://Reuma.pt). Molecular genetic testing to detect GLA gene mutations was performed. After the multiplex polymerase chain reactions technique for DNA amplification, direct sequencing of the complete sequence of GLA gene was completed. From a cohort of 292 patients with JIA (188 females, 104 males), mutations were identified in 5 patients (all female). Four patients had the mutation D313Y, a rare GLA variant, which is associated with low enzymatic levels in plasma, but normal lysosomal levels. One patient presented the missense mutation R118C, which was previously described in Mediterranean patients with FD. This is the first screening of FD mutations in a cohort of JIA patients. No “classic” pathogenic FD mutations were reported. The late-onset FD-associated mutation, R118C, was found in a frequency of 0.34% (1/292). PMID:28299312

  8. Genetic Screening of Mutations Associated with Fabry Disease in a Nationwide Cohort of Juvenile Idiopathic Arthritis Patients.

    PubMed

    Gonçalves, Maria J; Mourão, Ana F; Martinho, António; Simões, Olívia; Melo-Gomes, José; Salgado, Manuel; Estanqueiro, Paula; Ribeiro, Célia; Brito, Iva; Fonseca, João E; Canhão, Helena

    2017-01-01

    Fabry's disease (FD) is a lysosomal storage disorder associated with an alpha-galactosidase A deficiency. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients with established diagnosis is unknown, but as musculoskeletal pain may be an important complaint at presentation, misdiagnosed cases are anticipated. With this study, we aim to calculate the frequency of FD-associated mutations in a cohort of JIA patients. Children with JIA from a national cohort were selected. Clinical and laboratorial information was recorded in the Portuguese rheumatic diseases register (http://Reuma.pt). Molecular genetic testing to detect GLA gene mutations was performed. After the multiplex polymerase chain reactions technique for DNA amplification, direct sequencing of the complete sequence of GLA gene was completed. From a cohort of 292 patients with JIA (188 females, 104 males), mutations were identified in 5 patients (all female). Four patients had the mutation D313Y, a rare GLA variant, which is associated with low enzymatic levels in plasma, but normal lysosomal levels. One patient presented the missense mutation R118C, which was previously described in Mediterranean patients with FD. This is the first screening of FD mutations in a cohort of JIA patients. No "classic" pathogenic FD mutations were reported. The late-onset FD-associated mutation, R118C, was found in a frequency of 0.34% (1/292).

  9. Genetic screening of patients with medullary thyroid cancer in a referral center in Greece during the past two decades.

    PubMed

    Sarika, H-L; Papathoma, A; Garofalaki, M; Saltiki, K; Pappa, T; Pazaitou-Panayiotou, K; Anastasiou, E; Alevizaki, M

    2015-04-01

    Mutations in the RET gene are responsible for hereditary medullary thyroid cancer (MTC) and may vary between ethnic groups. We report the spectrum of mutations detected in patients with MTC in a referral center in Greece. Screening for RET mutations was performed in 313 subjects from 188 unrelated families: 51 patients had clinical suspicion for familial disease, 133 were apparently sporadic, four patients had only C cell hyperplasia, and 125 were family members. Exons 8, 10, 11, and 13-16 were screened. A total of 58 individuals (30.85%) were RET mutations carriers, 120 (63.8%) were finally classified as sporadic, 13 apparently sporadic cases (9.8%) were identified with RET mutation: ten carried the exon 8 at codon 533 mutation (previously reported), two the exon 14 at codon 804 mutation, and one the exon 13 at codon 768 mutation. Six patients (3.19%) with clinical features of multiple endocrine neoplasia type 2A and negative for RET mutations were classified as 'unknown cause'. The mutations of hereditary cases were as follows: 21 cases (36.2%) in exon 8 codon 533, 19 (32.8%) in exon 11 codon 634, nine (15.5%) in exon 10, five (8.6%) in exon 16, three (5.2%) in exon 14 codon 804, and one in exon 13 codon 768 (1.7%). The spectrum of RET mutations in Greece differs from that in other populations and the prevalence of familial cases is higher. The exon 8 (Gly533Cys) mutation was the most prevalent in familial cases unlike other series, followed by exon 11 (codon 634) mutations which are the most frequent elsewhere. The wide application of genetic screening in MTC reveals new molecular defects and helps to characterize the spectrum of mutations in each ethnic group. © 2015 European Society of Endocrinology.

  10. A genetic screen of the mutations in the Korean patients with early-onset Alzheimer’s disease

    PubMed Central

    An, Seong Soo; Park, Sun Ah; Bagyinszky, Eva; Bae, Sun Oh; Kim, Yoon-Jeong; Im, Ji Young; Park, Kyung Won; Park, Kee Hyung; Kim, Eun-Joo; Jeong, Jee Hyang; Kim, Jong Hun; Han, Hyun Jeong; Choi, Seong Hye; Kim, SangYun

    2016-01-01

    Early-onset Alzheimer’s disease (EOAD) has distinct clinical characteristics in comparison to late-onset Alzheimer’s disease (LOAD). The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS) study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer’s disease (AD) mutations in the consecutive EOAD subjects from the CREDOS study from April 2012 to February 2014. We checked the sequence of APP (exons 16–17), PSEN1 (exons 3–12), and PSEN2 (exons 3–12) genes. We identified different causative or probable pathogenic AD mutations, PSEN1 T116I, PSEN1 L226F, and PSEN2 V214L, employing 24 EOAD subjects with a family history and 80 without a family history of dementia. PSEN1 T116I case demonstrated autosomal dominant trait of inheritance, with at least 11 affected individuals over 2 generations. However, there was no family history of dementia within first-degree relation in PSEN1 L226F and PSEN2 V214L cases. Approximately, 55.7% of the EOAD subjects had APOE ε4 allele, while none of the mutation-carrying subjects had the allele. The frequency of genetic mutation in this study is lower compared to the studies from other countries. The study design that was based on nationwide cohort, which minimizes selection bias, is thought to be one of the contributors to the lower frequency of genetic mutation. However, the possibility of the greater likeliness of earlier onset of sporadic AD in Korea cannot be

  11. Genetic screening services provided in Turkey.

    PubMed

    Erdem, Yurdagül; Tekşen, Fulya

    2013-12-01

    In Turkey, the rate of consanguineous marriage is quite high (22-24 %) and as a result, the incidence of autosomal recessive diseases and congenital anomalies is also very high and gives rise to a serious public health problem. In the last three decades, great effort has been made to avoid increases in the prevalence of these hereditary diseases. For this purpose, population-based premarital, prenatal, neonatal and adult genetic screening programs are performed in various centers such as Community Health Centers, Early Diagnosis of Cancer and Education Centers (KETEM), Prenatal and Neonatal Departments of Universities and State Hospitals and Thalessemia Screening Centers. Such centers are staffed by health professionals including physicians, family physicians, nurses, midwives, biologists and medical geneticists. Genetic counseling is also provided to patients attending these centers after screening tests are performed. Since there are no specialized training programs for genetic counselors, genetic counseling is generally provided by doctors or medical geneticists. The aim of this paper is to give an overview of the genetic screening services provided in Turkey, the prevalence of genetic diseases and the design of intensive educational programs for health professionals.

  12. How do patient perceived determinants influence the decision-making process to accept or decline preimplantation genetic screening?

    PubMed

    Gebhart, Marty Brown; Hines, Randall S; Penman, Alan; Holland, Aimee Chism

    2016-01-01

    Identify the determinants that influence the patient's decision-making process when deciding to accept or decline preimplantation genetic screening (PGS) in a given IVF cycle. Pilot, retrospective, cross-sectional study that used a questionnaire containing a combination of quantitative and qualitative items. Private practice IVF clinic. Patients and partners initiating an IVF treatment cycle, both autologous and donor, between October 2012 and January 2015. None. Identification of patient perceived determinants and the importance of each on the decision to accept or decline PGS. Responses from the questionnaire (N = 117) were returned, and of these, 60% accepted PGS. The female response rate was 75% (N = 88) and the male response rate was 25% (N = 29). Ninety-eight percent were Christian (N = 112) and 88% college educated (N = 102) with 39% (N = 40) having some postgraduate education. Sixty-eight percent (N = 79) had no knowledge of PGS before the IVF cycle; however, after provider education, 92% (N = 108) correctly identified that PGS was elective and 93% (N = 109) reported sufficient knowledge to make an informed decision to accept or decline PGS. The additional cost of screening, the provider information and influence, and social support or acceptance from partner, family, and/or friends, were the three statistically significant variables affecting the decision. This is the first study, to the authors' knowledge, to identify and assess the determinants of the patient decision-making process when presented with the choice of PGS. Several factors contribute to the patient-perceived determinants when choosing to accept or decline PGS, including cost, religious and ethical beliefs and values, social and family support, provider influences, and the past reproductive experience of the patient. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Prenatal screening for chromosomal abnormalities in IVF patients that opted for preimplantation genetic screening/diagnosis (PGS/D): a need for revised algorithms in the era of personalized medicine.

    PubMed

    Takyi, Afua; Santolaya-Forgas, Joaquin

    2017-06-01

    Obstetricians offer prenatal screening for most common chromosomal abnormalities to all pregnant women including those that had in vitro fertilization (IVF) and preimplantation genetic screening/diagnosis (PGS/D). We propose that free fetal DNA in maternal circulation together with the second trimester maternal serum alfa feto protein (MSAFP) and ultrasound imaging is the best prenatal screening test for chromosomal abnormalities and congenital anomalies in IVF-PGD/S patients because risk estimations from all other prenatal screening algorithms for chromosomal abnormalities depend heavily on maternal age which is irrelevant in PGS/D patients.

  14. Genetic screening analysis of patients with hereditary diffuse gastric cancer from northern and northeastern Brazil

    PubMed Central

    2014-01-01

    Background Hereditary diffuse gastric cancer (HDGC) is a hereditary autosomal inherited syndrome associated with CDH1 germline mutations. In Brazil, gastrointestinal tumors are among the most prevalent tumor types and constitute a serious public health problem, especially in the northern and northeastern regions. This study aimed to investigate germline mutations, methylation pattern and genomic rearrangements in the CDH1 gene and quantitative changes in the DNA of HDGC patients in northern and northeastern Brazil. Methods Twenty-seven DNA samples from the members of four families affected by HDGC were analyzed using array comparative genomic hybridization (aCGH), DNA sequencing and methylation pattern. Results No evidence of gain and loss events or any rearrangements were found in any of the samples tested using aCGH. No promoter region hypermethylation was observed either. Two of the four families presented different types of germline mutations. The 185G > T and 1018A > G germline mutations detected in this study have been described in Asian and European families, respectively. The ancestors of the two families carrying these mutations had originated from those continents. Conclusion This is the first study to evaluate CDH1 gene germline mutations in Brazilian families with HDGC. In our study, 50% of the families showed no CDH1 gene alterations, and it is possible that in regions with a high incidence of gastric cancer, such as northern and northeastern Brazil, environmental factors might have induced the different genetic alterations analyzed in this study. PMID:25180051

  15. Genetic screening test for psoriatic arthritis and UVB irradiation potential responders: A new tool to identify psoriasis subpopulation patients?

    PubMed Central

    Lotti, Torello; Tognetti, Linda; Galeone, Massimiliano; Bruscino, Nicola; Moretti, Silvia; Giorgini, Simonetta

    2011-01-01

    Psoriatic arthritis (PsA) is a psoriasis-associated inflammatory disease of the joints and enthuses. The occurrence of PsA is linked to the complex interplay of gene environment, and immune system. Genetic factors have long been recognized to play an important role in PsA. Genes within the major histocompatibility complex (MHC) region have been shown to be associated with PsA. These include genes coded in the HLA region, (especially Class I antigens) and non-HLA genes (i.e., MHC class I chain-related antigen A, MICA, and TNF-α genes). Association studies in PsA have also identified a number of genes outside MHC region, including interleukin-1 (IL-1) gene cluster, killer-cell immunoglobulin-like receptors (KIRs), and IL-23R genes. Established systemic treatments for moderate-severe psoriasis and PsA may be potentially dangerous and usually time consuming for the patient and often expensive for the National Health Systems. Tests which could predict which subset of psoriatic patients could develop the most severe forms of the disease (i.e., PsA) or will respond to well-established (UVB irradiation) or other systemic treatments are now required. The goal of genetic test screening is to rapidly and safely identify subjects for preventive or early treatment or extended surveillance prior to the onset of signs and symptoms. Genetic tests today represent a reliable investigation procedure which could rapidly and consistently improve the diagnostic ability of the dermatologist and contribute to the early and correct treatment of the different subsets of PsA. PMID:23130225

  16. Technical Update: Preimplantation Genetic Diagnosis and Screening.

    PubMed

    Dahdouh, Elias M; Balayla, Jacques; Audibert, François; Wilson, R Douglas; Audibert, François; Brock, Jo-Ann; Campagnolo, Carla; Carroll, June; Chong, Karen; Gagnon, Alain; Johnson, Jo-Ann; MacDonald, William; Okun, Nanette; Pastuck, Melanie; Vallée-Pouliot, Karine

    2015-05-01

    technologies. Preimplantation genetic diagnosis is an alternative to prenatal diagnosis for the detection of genetic disorders in couples at risk of transmitting a genetic condition to their offspring. Preimplantation genetic screening is being proposed to improve the effectiveness of in vitro fertilization by screening for embryonic aneuploidy. Though FISH-based PGS showed adverse effects on IVF success, emerging evidence from new studies using comprehensive chromosome screening technology appears promising. Recommendations 1. Before preimplantation genetic diagnosis is performed, genetic counselling must be provided by a certified genetic counsellor to ensure that patients fully understand the risk of having an affected child, the impact of the disease on an affected child, and the benefits and limitations of all available options for preimplantation and prenatal diagnosis. (III-A) 2. Couples should be informed that preimplantation genetic diagnosis can reduce the risk of conceiving a child with a genetic abnormality carried by one or both parents if that abnormality can be identified with tests performed on a single cell or on multiple trophectoderm cells. (II-2B) 3. Invasive prenatal or postnatal testing to confirm the results of preimplantation genetic diagnosis is encouraged because the methods used for preimplantation genetic diagnosis have technical limitations that include the possibility of a false result. (II-2B) 4. Trophectoderm biopsy has no measurable impact on embryo development, as opposed to blastomere biopsy. Therefore, whenever possible, trophectoderm biopsy should be the method of choice in embryo biopsy and should be performed by experienced hands. (I-B) 5. Preimplantation genetic diagnosis of single-gene disorders should ideally be performed with multiplex polymerase chain reaction coupled with trophectoderm biopsy whenever available. (II-2B) 6. The use of comprehensive chromosome screening technology coupled with trophectoderm biopsy in preimplantation

  17. First Genetic Screening for Maternal Uniparental Disomy of Chromosome 7 in Turkish Silver-Russell Syndrome Patients

    PubMed Central

    Karaca, Emin; Tuysuz, Beyhan; Pehlivan, Sacide; Ozkinay, Ferda

    2012-01-01

    Objective Silver–Russell syndrome (SRS) is a clinically and genetically heterogeneous syndrome which is characterized by severe intrauterine and postnatal growth retardation, and typical characteristic facial dysmorphisms. It has been associated with maternal uniparental disomy (UPD) for chromosome 7 and hypomethylation of imprinting control region 1 (IGF2/H19) in 11p15. UPD refers to the situation in which both copies of a chromosome pair have originated from one parent. UPD can be presented both as partial heterodisomy and isodisomy. The aim of this study was to determine the maternal UPD7 (matUPD7) in 13 Turkish SRS patients. Methods Genotyping for matUPD7 was performed with microsatellite markers by polymerase chain reaction. Findings The maternal UPD7 including the entire chromosome was identified in 1/13 (7.6%) of individuals within SRS patients. There were no significant differences between clinical features of matUPD7 case and other SRS cases except congenital heart defects. Conclusion It is often difficult to establish diagnosis of a child with intrauterine growth retardation (IUGR), growth failure and dysmorphic features. Thus, screening for matUPD7 in IUGR children with growth failure and mild SRS features might be a valuable diagnostic tool. PMID:23429302

  18. Design of a randomized controlled trial for genomic carrier screening in healthy patients seeking preconception genetic testing.

    PubMed

    Kauffman, Tia L; Wilfond, Benjamin S; Jarvik, Gail P; Leo, Michael C; Lynch, Frances L; Reiss, Jacob A; Richards, C Sue; McMullen, Carmit; Nickerson, Deborah; Dorschner, Michael O; Goddard, Katrina A B

    2017-02-01

    Population-based carrier screening is limited to well-studied or high-impact genetic conditions for which the benefits may outweigh the associated harms and costs. As the cost of genome sequencing declines and availability increases, the balance of risks and benefits may change for a much larger number of genetic conditions, including medically actionable additional findings. We designed an RCT to evaluate genomic clinical sequencing for women and partners considering a pregnancy. All results are placed into the medical record for use by healthcare providers. Through quantitative and qualitative measures, including baseline and post result disclosure surveys, post result disclosure interviews, 1-2year follow-up interviews, and team journaling, we are obtaining data about the clinical and personal utility of genomic carrier screening in this population. Key outcomes include the number of reportable carrier and additional findings, and the comparative cost, utilization, and psychosocial impacts of usual care vs. genomic carrier screening. As the study progresses, we will compare the costs of genome sequencing and usual care as well as the cost of screening, pattern of use of genetic or mental health counseling services, number of outpatient visits, and total healthcare costs. This project includes novel investigation into human reactions and responses from would-be parents who are learning information that could both affect a future pregnancy and their own health.

  19. Newborn genetic screening: blessing or curse?

    PubMed

    Kenner, C; Amlung, S

    1999-10-01

    Newly discovered genes and advances in genetic screening programs prompt many questions reflecting the kinds of ethical dilemmas that go hand in hand with life-changing discoveries. Neonatal genetic screening has been a standard of care for some time, but as our knowledge in the field of genetics expands, should we continue with the same approach? What newborn genetic screening tests should be mandatory, and what are the long-range consequences associated with testing? This article reviews genetic modes of inheritance, outlines and explains the most common newborn screening tests, and enumerates the ethical issues associated with these screening procedures. The role of the neonatal nurse in the newborn genetic screening process is discussed.

  20. A common genetic variant of fucosyltransferase 2 correlates with serum carcinoembryonic antigen levels and affects cancer screening in patients with primary sclerosing cholangitis

    PubMed Central

    Wannhoff, Andreas; Folseraas, Trine; Brune, Maik; Rupp, Christian; Friedrich, Kilian; Knierim, Johannes; Weiss, Karl Heinz; Sauer, Peter; Flechtenmacher, Christa; Schirmacher, Peter; Stremmel, Wolfgang; Hov, Johannes R

    2015-01-01

    Background Primary sclerosing cholangitis (PSC) patients are at increased risk of biliary tract cancer, and carcinoembryonic antigen (CEA) serum levels might be used for screening. Objective To examine cancer screening with CEA in PSC patients and analyse how serum CEA levels are affected by genetic variants of fucosyltransferase (FUT) 2 and 3. Methods In a retrospective cohort analysis we evaluated CEA levels in 226 PSC patients, including 19 with biliary malignancy, and investigated how FUT2 and FUT3 SNPs affected CEA levels. Receiver-operating-characteristic (ROC) analysis was performed and cut-off values were determined based on Youden’s index. A control cohort contained 240 patients, including 28 with biliary malignancy. Results Median CEA concentration was lower in cancer-free patients (1.4 ng/mL) than in cancer patients (2.0 ng/mL, P = 0.014). ROC analysis revealed an area under the curve (AUC) of 0.671, the optimal cut-off was 3.2 ng/mL. The FUT2 variant rs601338 (G428A) correlated with CEA levels, and the effect was most prominent in a subgroup of patients genetically incapable of expressing CA19-9. The AUC improved if ROC analysis was performed separately for wild-type (AUC: 0.731) and homozygous mutant (AUC: 0.816) G428A. The influence of FUT2 on CEA was confirmed in the control cohort. Conclusions CEA is interesting for biliary-malignancy screening in PSC patients, especially in patients who do not express CA19-9. This is the first study to show that the combined use of CEA measurement and FUT genotyping is clinically beneficial and that it might enhance the early detection of biliary malignancy in clinical practice. This approach could also be effective when screening for other common gastrointestinal malignancies. PMID:26966527

  1. Genetic screening in patients of reproductive age. How do you advise prospective parents who want to know specific risks?

    PubMed

    Wheeler, P G; Bianchi, D W

    2000-05-15

    At times, determining the actual genetic condition occurring in a family can be very difficult. The most important steps in deciding when testing is appropriate are the patient's age and family history, with special attention to ethnic background. By identifying risk factors before pregnancy, prospective parents can be fully informed about their specific risk of having a child with a genetic condition. Furthermore, the pros and cons of invasive prenatal diagnostic procedures often can be fully discussed well in advance of an actual pregnancy. Clinical geneticists and genetic counselors can provide valuable assistance when difficult questions or problems arise.

  2. Population genetic screening programmes: principles, techniques, practices, and policies.

    PubMed

    Godard, Béatrice; ten Kate, Leo; Evers-Kiebooms, Gerry; Aymé, Ségolène

    2003-12-01

    This paper examines the professional and scientific views on the principles, techniques, practices, and policies that impact on the population genetic screening programmes in Europe. This paper focuses on the issues surrounding potential screening programmes, which require further discussion before their introduction. It aims to increase, among the health-care professions and health policy-makers, awareness of the potential screening programmes as an issue of increasing concern to public health. The methods comprised primarily the review of the existing professional guidelines, regulatory frameworks and other documents related to population genetic screening programmes in Europe. Then, the questions that need debate, in regard to different types of genetic screening before and after birth, were examined. Screening for conditions such as cystic fibrosis, Duchenne muscular dystrophy, familial hypercholesterolemia, fragile X syndrome, hemochromatosis, and cancer susceptibility was discussed. Special issues related to genetic screening were also examined, such as informed consent, family aspects, commercialization, the players on the scene and monitoring genetic screening programmes. Afterwards, these questions were debated by 51 experts from 15 European countries during an international workshop organized by the European Society of Human Genetics Public and Professional Policy Committee in Amsterdam, The Netherlands, 19-20, November, 1999. Arguments for and against starting screening programmes have been put forward. It has been questioned whether genetic screening differs from other types of screening and testing in terms of ethical issues. The general impression on the future of genetic screening is that one wants to 'proceed with caution', with more active impetus from the side of patients' organizations and more reluctance from the policy-makers. The latter try to obviate the potential problems about the abortion and eugenics issues that might be perceived as a

  3. Mutations of the GLA gene in young patients with stroke: the PORTYSTROKE study--screening genetic conditions in Portuguese young stroke patients.

    PubMed

    Baptista, Miguel Viana; Ferreira, Susana; Pinho-E-Melo, Teresa; Carvalho, Marta; Cruz, Vítor T; Carmona, Cátia; Silva, Fernando A; Tuna, Assunção; Rodrigues, Miguel; Ferreira, Carla; Pinto, Ana A N; Leitão, André; Gabriel, João Paulo; Calado, Sofia; Oliveira, João Paulo; Ferro, José M

    2010-03-01

    Fabry disease is an X-linked monogenic disorder caused by mutations in the GLA gene. Recent data suggest that stroke in young adults may be associated with Fabry disease. We aimed to ascertain the prevalence of this disorder among young adult patients with stroke in Portugal by GLA genotyping. During 1 year, all patients aged 18 to 55 years with first-ever stroke, who were admitted into any of 12 neurology hospital departments in Portugal, were prospectively enrolled (n=625). Ischemic stroke was classified according to Trial of Org 10172 in Acute Stroke Treatment criteria. Alpha-galactosidase activity was further assayed in all patients with GLA mutations. Four hundred ninety-three patients (mean age, 45.4 years; 61% male) underwent genetic analyses: 364 with ischemic stroke, 89 with intracerebral hemorrhage, 26 with subarachnoid hemorrhage, and 14 with cerebral venous thrombosis. Twelve patients had missense GLA mutations: 9 with ischemic stroke (p.R118C: n=4; p.D313Y: n=5), including 5 patients with an identified cause of stroke (cardiac embolism: n=2; small vessel disease: n=2; other cause: n=1), 2 with intracerebral hemorrhage (p.R118C: n=1; p.D313Y: n=1), and one with cerebral venous thrombosis (p.R118C: n=1). Leukocyte alpha-galactosidase activity was subnormal in the hemizygous males and subnormal or low-normal in the heterozygous females. Estimated prevalence of missense GLA mutations was 2.4% (95% CI, 1.3% to 4.1%). Despite a low diagnostic yield, screening for GLA mutations should probably be considered in different types of stroke. Restricting investigation to patients with cryptogenic stroke may underestimate the true prevalence of Fabry disease in young patients with stroke.

  4. The genetic spectrum and the evaluation of CADASIL screening scale in Chinese patients with NOTCH3 mutations.

    PubMed

    Liu, Xiao; Zuo, Yuehuan; Sun, Wei; Zhang, Wei; Lv, He; Huang, Yining; Xiao, Jiangxi; Yuan, Yun; Wang, Zhaoxia

    2015-07-15

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small artery disease caused by NOTCH3 gene mutation. Here we report clinical, pathological and genetic profiles of 29 newly-diagnosed CADASIL patients, evaluation of the CADASIL scale in Chinese CADASIL patients, and reanalysis of all reported mainland Chinese patients with identified NOTCH3 gene mutation. We found two novel mutations (p.C134G and p.C291Y) and 13 reported NOTCH3 mutations in the newly-diagnosed group. CADASIL scale score was less than the cutoff score in 19 of 53 Chinese patients with NOTCH3 mutation, generating only a sensitivity of 64.1%. At the time of study, the total number of genetically confirmed CADASIL cases reached 158 from 97 unrelated mainland Chinese families, with 9/97 (9.3%) sporadic patients. The NOTCH3 gene mutation profile showed 43 mutations, with hotspots in exon 4, followed by exon 3. The considerable variability in onset age and CADASIL scale score in patients carrying the same NOTCH3 missense mutation suggested no obvious phenotype-genotype correlation. In conclusion, we report two novel mutations which expand the NOTCH3 mutational spectrum. Exons 4 and 3 are hotspots in mainland Chinese patients with NOTCH3 mutation. The low sensitivity of CADASIL scale in our patients group indicated that the CADASIL scale should be refined according to the clinical characteristics of Chinese CADASIL patients when used in Chinese populations.

  5. Emergency preparedness for newborn screening and genetic services.

    PubMed

    Pass, Kenneth A; Thoene, Jess; Watson, Michael S

    2009-06-01

    Patients identified in newborn screening programs can be among the most vulnerable during a disaster due to their need to have prompt diagnosis and medical management. Recent disasters have challenged the ability of newborn screening programs to maintain the needed continuity during emergency situations. This has significant implications for the newborn screening laboratories, the diagnostic confirmation providers, and the patients who either require diagnosis or maintenance of their therapeutic interventions. In 2007, the National Coordinating Center (NCC) for the Regional Genetics and Newborn Screening Collaboratives (RCs) sponsored a meeting involving representatives of the Regional Genetics and Newborn Screening Collaborative Groups, state newborn screening programs, providers of diagnosis and confirmation services, manufacturers of equipment, medical foods, and other treatments used in patients identified in newborn screening programs, and individuals from agencies involved in disaster response including the National Disaster Medical Service, the Centers for Disease Control and Prevention, the Emergency Management Assistance Compact, the Federal Emergency Management Agency, and others. In addition to developing contingency plans for newborn screening, we have considered other uses of genetics as it is used in DNA-based kinship identification of mass casualties. The meeting resulted in the description of a wide range of issues facing newborn screening programs, provider groups, and patients for which emergency preparedness development is needed in order that appropriate response is enabled.

  6. Combined treatment with octreotide LAR and pegvisomant in patients with pituitary gigantism: clinical evaluation and genetic screening.

    PubMed

    Mangupli, Ruth; Rostomyan, Liliya; Castermans, Emilie; Caberg, Jean-Hubert; Camperos, Paul; Krivoy, Jaime; Cuauro, Elvia; Bours, Vincent; Daly, Adrian F; Beckers, Albert

    2016-10-01

    Pituitary gigantism is a rare condition caused by growth hormone secreting hypersecretion, usually by a pituitary tumor. Acromegaly and gigantism cases that have a genetic cause are challenging to treat, due to large tumor size and poor responses to some medical therapies (e.g. AIP mutation affected cases and those with X-linked acrogigantism syndrome). We performed a retrospective study to identify gigantism cases among 160 somatotropinoma patients treated between 1985 and 2015 at the University Hospital of Caracas, Venezuela. We studied clinical details at diagnosis, hormonal responses to therapy and undertook targeted genetic testing. Among the 160 cases, eight patients (six males; 75 %) were diagnosed with pituitary gigantism and underwent genetic analysis that included array comparative genome hybridization for Xq26.3 duplications. All patients had GH secreting pituitary macroadenomas that were difficult to control with conventional treatment options, such as surgery or primary somatostatin receptor ligand (SRL) therapy. Combined therapy (long-acting SRL and pegvisomant) as primary treatment or after pituitary surgery and radiotherapy permitted the normalization of IGF-1 levels and clinical improvement. Novel AIP mutations were the found in three patients. None of the patients had Xq26.3 microduplications. Treatment of pituitary gigantism is frequently challenging; delayed control increases the harmful effects of GH excess, such as, excessive stature and symptom burden, so early diagnosis and effective treatment are particularly important in these cases.

  7. Clinically guided genetic screening in a large cohort of italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas.

    PubMed

    Mannelli, Massimo; Castellano, Maurizio; Schiavi, Francesca; Filetti, Sebastiano; Giacchè, Mara; Mori, Luigi; Pignataro, Viviana; Bernini, Gianpaolo; Giachè, Valentino; Bacca, Alessandra; Biondi, Bernadette; Corona, Giovanni; Di Trapani, Giuseppe; Grossrubatscher, Erika; Reimondo, Giuseppe; Arnaldi, Giorgio; Giacchetti, Gilberta; Veglio, Franco; Loli, Paola; Colao, Annamaria; Ambrosio, Maria Rosaria; Terzolo, Massimo; Letizia, Claudio; Ercolino, Tonino; Opocher, Giuseppe

    2009-05-01

    The aim of the study was to define the frequency of hereditary forms and the genotype/phenotype correlations in a large cohort of Italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas. We examined 501 consecutive patients with pheochromocytomas and/or paragangliomas (secreting or nonsecreting). Complete medical and family histories, as well as the results of clinical, laboratory, and imaging studies, were recorded in a database. Patients were divided into different groups according to their family history, the presence of lesions outside adrenals/paraganglia considered syndromic for VHL disease, MEN2, and NF1, and the number and types of pheochromocytomas and/or paragangliomas. Germ-line mutations in known susceptibility genes were investigated by gene sequencing (VHL, RET, SDHB, SDHC, SDHD) or diagnosed according to phenotype (NF1). In 160 patients younger than 50 yr with a wild-type profile, multiplex ligation-dependent probe amplification assays were performed to detect genomic rearrangements. Germline mutations were detected in 32.1% of cases, but frequencies varied widely depending on the classification criteria and ranged from 100% in patients with associated syndromic lesions to 11.6% in patients with a single tumor and a negative family history. The types and number of pheochromocytomas/paragangliomas as well as age at presentation and malignancy suggest which gene should be screened first. Genomic rearrangements were found in two of 160 patients (1.2%). The frequency of the hereditary forms of pheochromocytoma/paraganglioma varies depending on the family history and the clinical presentation. A positive family history and an accurate clinical evaluation of patients are strong indicators of which genes should be screened first.

  8. New perspectives on preimplantation genetic diagnosis and preimplantation genetic screening.

    PubMed

    Chen, Chun-Kai; Yu, Hsing-Tse; Soong, Yung-Kuei; Lee, Chyi-Long

    2014-06-01

    Preimplantation genetic diagnosis is a procedure that involves the removal of one or more nuclei from oocytes (a polar body) or embryos (blastomeres or trophectoderm cells) in order to test for problems in genome sequence or chromosomes of the embryo prior to implantation. It provides new hope of having unaffected children, as well as avoiding the necessity of terminating an affected pregnancy for genetic parents who carry an affected gene or have balanced chromosomal status. Polymerase chain reaction-based molecular techniques are the methods used to detect gene defects with a known sequence and X-linked diseases. The indication for using this approach has expanded for couples who are prevented from having babies because they carry a serious genetic disorder to couples with conditions that are not immediately life threatening, such as cancer predisposition genes and Huntington disease. In addition, fluorescent in situ hybridization (FISH) has been widely applied for the detection of chromosome abnormalities. FISH allows the evaluation of many chromosomes at the same time, up to 15 chromosome pairs in a single cell. Preimplantation genetic screening, defined as a test that screens for aneuploidy, has been most commonly used in situations of advanced maternal age, a history of recurrent miscarriage, a history of repeated implantation failure, or a severe male factor. Unfortunately, randomized controlled trials have as yet shown no benefit with respect to preimplantation genetic screening using cleavage stage biopsy, which is probably attributable to the high levels of mosaicism at early cleavage stages and the limitations of FISH. Recently, two main types of array-based technology combined with whole genome amplification have been developed for use in preimplantation genetic diagnosis; these are comparative genomic hybridization and single nucleotide polymorphism-based arrays. Both allow the analysis of all chromosomes, and the latter also allows the haplotype of

  9. Recent advances in prenatal genetic screening and testing.

    PubMed

    Van den Veyver, Ignatia B

    2016-01-01

    The introduction of new technologies has dramatically changed the current practice of prenatal screening and testing for genetic abnormalities in the fetus. Expanded carrier screening panels and non-invasive cell-free fetal DNA-based screening for aneuploidy and single-gene disorders, and more recently for subchromosomal abnormalities, have been introduced into prenatal care. More recently introduced technologies such as chromosomal microarray analysis and whole-exome sequencing can diagnose more genetic conditions on samples obtained through amniocentesis or chorionic villus sampling, including many disorders that cannot be screened for non-invasively. All of these options have benefits and limitations, and genetic counseling has become increasingly complex for providers who are responsible for guiding patients in their decisions about screening and testing before and during pregnancy.

  10. Recent advances in prenatal genetic screening and testing

    PubMed Central

    Van den Veyver, Ignatia B.

    2016-01-01

    The introduction of new technologies has dramatically changed the current practice of prenatal screening and testing for genetic abnormalities in the fetus. Expanded carrier screening panels and non-invasive cell-free fetal DNA-based screening for aneuploidy and single-gene disorders, and more recently for subchromosomal abnormalities, have been introduced into prenatal care. More recently introduced technologies such as chromosomal microarray analysis and whole-exome sequencing can diagnose more genetic conditions on samples obtained through amniocentesis or chorionic villus sampling, including many disorders that cannot be screened for non-invasively. All of these options have benefits and limitations, and genetic counseling has become increasingly complex for providers who are responsible for guiding patients in their decisions about screening and testing before and during pregnancy. PMID:27853526

  11. Culture and genetic screening in Africa.

    PubMed

    Jegede, Ayodele S

    2009-12-01

    Africa is a continent in transition amidst a revival of cultural practices. Over previous years the continent was robbed of the benefits of medical advances by unfounded cultural practices surrounding its cultural heritage. In a fast moving field like genetic screening, discussions of social and policy aspects frequently need to take place at an early stage to avoid the dilemma encountered by Western medicine. This paper, examines the potential challenges to genetic screening in Africa. It discusses how cultural practices may affect genetic screening. It views genomics science as a culture which is trying to diffuse into another one. It argues that understanding the existing culture will help the diffusion process. The paper emphasizes the importance of genetic screening for Africa, by assessing the current level of burden of diseases in the continent and shows its role in reducing disease prevalence. The paper identifies and discusses the cultural challenges that are likely to confront genetic screening on the continent, such as the worldview, rituals and taboos, polygyny, culture of son preference and so on. It also discusses cultural practices that may promote the science such as inheritance practices, spouse selection practices and naming patterns. Factors driving the cultural challenges are identified and discussed, such as socialization process, patriarchy, gender, belief system and so on. Finally, the paper discusses the way forward and highlights the ethical considerations of doing genetic screening on the continent. However, the paper also recognizes that African culture is not monolithic and therefore makes a case for exceptions.

  12. Development of an interactive computer-assisted instruction (ICAI) program for patient prenatal genetic screening and carrier testing for use in clinical settings.

    PubMed

    Griffith, Jennifer M; Sorenson, James R; Jennings-Grant, Tracey; Fowler, Beth

    2005-11-01

    Educating patients on prenatal genetic screening and carrier testing in a timely and effective manner is faced with barriers including, providers' limited knowledge, and little time available to spend discussing screening and testing during a visit. This paper describes the use of cognitive response interviews (CRI) and usability testing (UT) in the development of an interactive computer assisted instruction (ICAI) program for use by prenatal patients in clinical settings. Lessons learned during the program development process included simplification of content and adaptation of navigational features in response to observations and interviews of a sample of patients representing the intended population. The resulting program functions as a targeted patient education program that maintains the level of medical information needed, as specified by professional practices guidelines, in a patient friendly format. In addition, this ICAI program functions as a research tool that can collect data on program effectiveness. Researchers developing other patient education programs will benefit from the lessons learned during development of this ICAI program by considering rephrasing of content to fit patient understanding, and adding navigational features to help further facilitate effective program use.

  13. Advances in preimplantation genetic diagnosis/screening.

    PubMed

    Yan, LiYing; Wei, Yuan; Huang, Jin; Zhu, XiaoHui; Shi, XiaoDan; Xia, Xi; Yan, Jie; Lu, CuiLing; Lian, Ying; Li, Rong; Liu, Ping; Qiao, Jie

    2014-07-01

    Preimplantation genetic diagnosis (PGD) gives couples who have a high risk of transmitting genetic disorders to their baby the chance to have a healthy offspring through embryo genetic analysis and selection. Preimplantation genetic screening (PGS) is an effective method to select euploid embryos that may prevent repeated implantation failure or miscarriage. However, how and to whom PGS should be provided is a controversial topic. The first successful case of PGD of a human being was reported in 1990, and there have been tremendous improvements in this technology since then. Both embryo biopsy and genetic technologies have been improved dramatically, which increase the accuracy and expand the indications of PGD/PGS.

  14. Ethical issues in preconception genetic carrier screening

    PubMed Central

    Kihlbom, Ulrik

    2016-01-01

    Population-based preconception genetic carrier screening programmes (PCS) with expanded panels are currently being developed in the Netherlands. This form of genetic screening for recessive traits differs from other forms of genetic testing and screening in that it is offered to persons not known to have an increased risk of being carriers of genetic traits for severe recessive diseases and in that they include tests for a large number of traits, potentially several hundred. This raises several ethical issues around justice, consequences, and autonomy. It will be argued that most of these ethical problems call for cautious reflection when setting up PCS and similar programmes within preconception care. It is moreover argued that it is ethically problematic to have an official aim and failing to mention possibly legitimate public aims that actually drive the development of PCS. PMID:27388477

  15. Genetic Screening of Pediatric Cavernous Malformations.

    PubMed

    Merello, Elisa; Pavanello, Marco; Consales, Alessandro; Mascelli, Samantha; Raso, Alessandro; Accogli, Andrea; Cama, Armando; Valeria, Capra; De Marco, Patrizia

    2016-10-01

    Cerebral cavernous malformations (CCMs) are vascular malformations mostly located within the central nervous system. Heterozygous loss of function mutations in CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10 genes are identified in about 90 % of familial cases of CCMs and two thirds of sporadic cases with multiple lesions. In this study, we performed genetic screening of a cohort of 31 patients, mainly pediatric. We analyzed the CCM1, CCM2, and CCM3 genes by multiplex ligation-dependent probe amplification (MLPA) and direct sequencing of exons and intronic boundaries. A total of 9 typical pathogenic loss-of-function mutations were identified in 10 out 31 patients (32 %). The 75 % of familial cases were mutated and the percentage reached to 85 % when we consider only pediatric cases. Detection rate in sporadic cases with multiple lesions was considerably lower (16 %). We identified a novel variant of CCM3, the c.130-131insT (p.R45Efs*8), in 1 pediatric sporadic case with multiple lesions that introduced a premature termination codon into the messenger RNA (mRNA), most likely leading to mRNA decay. Similar to other CCM pediatric series, the main symptoms associated to clinical debut consisted of cerebral hemorrhage. In conclusion, the penetrance of CCM mutations in familial pediatric cases is high (85 %). The genetic workup could improve clinical and genetic counseling in CCM patients. Moreover, we confirmed the high risk of hemorrhage in children with CCMs.

  16. Genetic screening and democracy: lessons from debating genetic screening criteria in the Netherlands.

    PubMed

    van El, Carla Geertruida; Pieters, Toine; Cornel, Martina

    2012-04-01

    Recent decades have witnessed increasing possibilities for genetic testing and screening. In clinical genetics, the doctor's office defined a secluded space for discussion of sensitive reproductive options in cases of elevated risk for genetic disorders in individuals or their offspring. When prenatal screening for all pregnant women became conceivable, the potential increase in scale made social and ethical concerns relevant for the whole of society. Whereas genetic testing in clinical genetic practice was widely accepted, prenatal screening at a population level met with unease. Concerns were raised regarding social pressure to screen: the sum of individual choice might result in a 'collective eugenics'. The government's involvement also raised suspicion: actively offering screening evoked associations with eugenic population policies from the first half of the 20th century. By reconstructing elements of policy and public debate on prenatal screening in the Netherlands from the past 30 years, this article discusses how the government has gradually changed its role in balancing the interest of the individual and the collective on genetic reproductive issues. Against a background of increasing knowledge about and demand for prenatal screening among the population, governmental policy changed from focusing on protection by banning screening toward facilitating screening in a careful and ethically sound way by providing adequate information, decision aids and quality assessment instruments. In the meanwhile, invigorating democracy in public debate may entail discussing concepts of 'the good life' in relation to living with or without impairments and dealing with genetic information about oneself or one's offspring.

  17. Miniaturizing 3D assay for high-throughput drug and genetic screens for small patient-derived tumor samples (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Rotem, Asaf; Garraway, Levi; Su, Mei-Ju; Basu, Anindita; Regev, Aviv; Struhl, Kevin

    2017-02-01

    Three-dimensional growth conditions reflect the natural environment of cancer cells and are crucial to be performed at drug screens. We developed a 3D assay for cellular transformation that involves growth in low attachment (GILA) conditions and is strongly correlated with the 50-year old benchmark assay-soft agar. Using GILA, we performed high-throughput screens for drugs and genes that selectively inhibit or increase transformation, but not proliferation. This phenotypic approach is complementary to our genetic approach that utilizes single-cell RNA-sequencing of a patient sample to identify putative oncogenes that confer sensitivity to drugs designed to specifically inhibit the identified oncoprotein. Currently, we are dealing with a big challenge in our field- the limited number of cells that might be extracted from a biopsy. Small patient-derived samples are hard to test in the traditional multiwell plate and it will be helpful to minimize the culture area and the experimental system. We managed to design a suitable microfluidic device for limited number of cells and perform the assay using image analysis. We aim to test drugs on tumor cells, outside of the patient body- and recommend on the ideal treatment that is tailored to the individual. This device will help to minimize biopsy-sampling volumes and minimize interventions in the patient's tumor.

  18. Lactose intolerance genetic testing: is it useful as routine screening? Results on 1426 south-central Italy patients.

    PubMed

    Santonocito, Concetta; Scapaticci, Margherita; Guarino, Donatella; Annicchiarico, Eleonora Brigida; Lisci, Rosalia; Penitente, Romina; Gasbarrini, Antonio; Zuppi, Cecilia; Capoluongo, Ettore

    2015-01-15

    Adult-type hypolactasia is a widespread condition throughout the world, causing lactose malabsorption. Several studies suggested that the identification of C/T-13910 and G/A-22018 mutations, located upstream the gene encoding the lactase-phlorizin hydrolase (LPH), is a useful tool for the differential diagnosis of hypolactasia. We evaluated the frequencies of C/T-13910 and G/A-22018 variants in a central-south Italian population and the usefulness of lactase deficiency genetic testing in the clinic practice. The genomic DNA of 1426 patients and 1000 healthy controls from central-south Italy was isolated from peripheral whole blood and genotyped for the C/T-13910 and G/A-22018 polymorphisms by high-resolution melting analysis (HRMA) and sequencing. The frequencies of genotypes in the 1426 patients analysed were as follows: 1077 CC/GG (75.5%), 287 CT/GA (20.1%), 24 TT/AA (1.7%), 38 CC/GA (2.7%). Only 64 out of 1426 (4.5%) performed also L-BHT test, 29 of which were negative for L-BHT also in presence of different genotypes. Among the 35 individuals with L-BHT positive, 34 were CC/GG and only one CT/GA. Although lactose genetic test is a good predictor of persistence/non-persistence lactase in specific population, its use in the central-south Italy population should be limited given the high prevalence of the CCGG diplotype in normal individuals. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Seeing Patients Through Genetic Lenses

    PubMed Central

    FELCONE, LINDA HULL

    2005-01-01

    Biotechnology is changing how doctors ‘see’ patients and disease processes. Optical probes and computer-assisted genetic screening tools let researchers peer into the structure and functions of cellular proteins on a molecular level. Soon, this clearer vision of individual patients will be available in the clinic, making drug and biologic treatments safer. These new lenses will push medicine toward risk prediction and away from acute intervention. PMID:23393472

  20. [The mutation spectrum of the GJB2 gene in Belarussian patients with hearing loss. Results of pilot genetic screening of hearing impairment in newborns].

    PubMed

    Bliznets, E A; Marcul', D N; Khorov, O G; Markova, T G; Poliakov, A V

    2014-02-01

    A total of 111 unrelated probands and their 8 sibs from Grodno oblast (Belarus) with bilateral isolated sensorineural hearing impairment were studied for the presence of mutations in the connexin 26--GJB2gene. Mutations were detected in 51 probands (46% of the sample). A significantly higher frequency of the GJB2gene mutations was observed in familial cases of the disease with the autosomal recessive type of inheritance (in 78% of families). Detected peculiarities of the GJB2 gene mutation spectrum demonstrated that use of the algorithm, which was developed for Russian patients, is optimal for the molecular study of patients from Be- larus. In the sample of patients with hearing loss, the highest (among other similar samples studied in the world) allele frequency of c.313_326de114 mutation (7% out of all pathological GJB2 alleles) was registered; Polish origin of this deletion was suggested. It was demonstrated that detection of the GJB2 gene mutation on only one patient's chromosome is insufficient to confirm a molecular genetic diagnosis of hearing loss of the DFNB1 genetic type (autosomal recessive hearing loss caused by the GJB2 gene mutations). Pilot screening in the presence of GJB2 gene mutations in newborns from Grodno oblast was conducted. The material from 235 children was studied during the screening; nine heterozygous carriers of the mutation were found. The c.35delG mutation was detected in a homozygous state in a single newborn (hearing loss of moderate severity was subsequently audiologically confirmed in this child).

  1. Population screening for genetic susceptibility to disease.

    PubMed Central

    Clarke, A.

    1995-01-01

    Genetic screening for susceptibility to common diseases, such as the common cancers, cardiovascular disease, and diabetes, may soon be technically feasible. Commercial interests should not be allowed to introduce such screening before proper evaluation or without adequate counselling and support. The evaluation of such testing should include psychosocial and medical outcomes and outcomes for those given low risks as well as high risks. These tests may distract attention away from environmental factors contributing to disease, for which social and political measures may be more appropriate than individualised susceptibility screening and lifestyle modification. PMID:7613325

  2. Pragmatic approaches to genetic screening.

    PubMed

    Mallia, Pierre; ten Have, Henk

    2005-01-01

    Pragmatic approaches to genetic testing are discussed and appraised. Whilst there are various schools of pragmatism, the Deweyan approach seems to be the most appreciated in bioethics as it allows a historical approach indebted to Hegel. This in turn allows the pragmatist to specify and balance principles in various contexts. There are problems with where to draw a line between what is referred to here as the micro- and macro-level of doing bioethics, unless one is simply to be classified as a principlist. Whilst most discussions on genetics occur at a macro level, most specifying must be done also at a micro level - the clinical encounter. Whilst pragmatism encourages us to understand better social and scientific factors and puts into perspective statements like 'playing God', doubts are raised about the 'consensus' process and how one can put aside fundamental values such as the moral status of the embryo on which there is general disagreement. If those doing pragmatism do not endorse these values, there seems to be little ground for process and compromise with those who do. It seems therefore that pragmatism cannot ignore values, even those which are not endorsed by everyone.

  3. Ultrasonography should not guide the timing of thyroidectomy in pediatric patients diagnosed with multiple endocrine neoplasia syndrome 2A through genetic screening.

    PubMed

    Morris, Lilah F; Waguespack, Steven G; Edeiken-Monroe, Beth S; Lee, Jeff E; Rich, Thereasa A; Ying, Anita K; Warneke, Carla L; Evans, Douglas B; Perrier, Nancy D; Grubbs, Elizabeth G

    2013-01-01

    American Thyroid Association (ATA) guidelines suggest that thyroidectomy can be delayed in some children with multiple endocrine neoplasia syndrome 2A (MEN2A) if serum calcitonin (Ct) and neck ultrasonography (US) are normal. We hypothesized that normal US would not exclude a final pathology diagnosis of medullary thyroid cancer (MTC). We retrospectively queried a MEN2A database for patients aged<18 years, diagnosed through genetic screening, who underwent preoperative US and thyroidectomy at our institution, comparing preoperative US and Ct results with pathologic findings. 35 eligible patients underwent surgery at median age of 6.3 (range 3.0-13.8) years. Mean MTC size was 2.9 (range 0.5-6.0) mm. The sensitivity of a US lesion≥5 mm in predicting MTC was 13% [95% confidence interval (CI) 2%, 40%], and the specificity was 95% [95% CI 75%, 100%]. Elevated Ct predicted MTC in 13/15 patients (sensitivity 87% [95% CI 60%, 98%], specificity 35% [95% CI 15%, 59%]). The area under the receiver operating characteristic curve (AUC) for using US lesion of any size to predict MTC was 0.50 [95% CI 0.33, 0.66], suggesting that US size has poor ability to discriminate MTC from non-MTC cases. The AUC for Ct level at 0.65 [95% CI 0.46, 0.85] was better than that of US but not age [AUC 0.62, 95% CI 0.42, 0.82]. In asymptomatic children with MEN2A diagnosed by genetic screening, preoperative thyroid US was not sensitive in identifying MTC of any size and, when determining the age for surgery, should not be used to predict microscopic MTC.

  4. Nutritional screening in surgical patients.

    PubMed

    Thompson, J S; Burrough, C A; Green, J L; Brown, G L

    1984-03-01

    Routine nutritional screening of patients admitted to the surgical services confirms a substantial prevalence of malnutrition. Identification of the malnourished patient and the patient who is likely to become malnourished should be done as early as possible in the hospital stay and usually requires only simple, readily available parameters. Nutritional screening is only the first step in the optimal nutritional management of surgical patients. This information should be used to determine the need for further nutritional assessment, the appropriate consultation, and nutritional therapy.

  5. [Current options of preimplantion genetic screening and preimplantation genetic diagnostics].

    PubMed

    Šimečková, V

    The aim of this work is to summarize the current knowledge about preimplantation genetic screening and diagnostics. A review article. Department of Gynecology and Obstetrics, District Hospital Šternberk, IVF Clinic, Olomouc. Preimplantation genetic testing is a complex of genetic and molecular cytogenetic examinations, which can help to detect abnormalities in embryos before transfer into the uterus of the mother. These specialized examinations are based on the latest findings in genetics and assisted reproduction. The preimplantation genetic testing is necessarily associated with a method of in vitro fertilization. It is performed on isolated blastomeres on the third day of embryo cultivation. Nowadays, it is preferred trophectoderm examination of cells from the five-day blastocysts. Generally speaking, after preimplantation genetic testing, we can select only embryos without genetic load to transfer into uterus. Preimplantation genetic testing is an important part of treatment of infertility. Complex diagnostics and treatment of infertile couples are increasingly influenced by the development and use of advanced genomic technologies. Further development and application of these modern methods require close cooperation between the field of assisted reproduction and clinical genetics.

  6. Genetic predisposition and screening in pediatric cancer.

    PubMed

    Pakakasama, Samart; Tomlinson, Gail E

    2002-12-01

    Pediatricians are often the health care providers who first detect the signs and symptoms of childhood cancer. Although pediatric malignancies are rare diseases, early diagnosis is an important factor leading to high cure rates of many types of cancers including retinoblastomara, Wilms' tumor, hepatoblastoma, rhabdomyosarcoma. thyroid carcinoma, and other solid tumors. A number of familial cancer syndromes present with childhood cancers that can be recognized or diagnosed by pediatricians. The genetic origins of several syndromes have been elucidated. Genetic testing is not yet available for all of these inherited cancers. A frequently updated list of genetic tests is available at www.genetests.org. The ordering and interpreting of genetic tests, however, is often best done by trained genetic counselors. The pediatrician will play a vital on-going role in following the at-risk child. In many of syndromes discussed, the cost effectiveness of the tests as well as that of any potential intervention needs further study. The role of the subtle genetic polymorphisms in pediatric tumorigenesis. many more of which will undoubtedly be described in the coming years, has not yet been translated into defined needs for interventions. Perhaps in the future it will be possible to understand the additive effect of multiple genetic polymorphisms and to determine genetic profiles of high cancer risk. Until suitable interventions are established, however, the study of genetic variability and cancer will await practical significance. Undoubtedly other major important cancer genes are yet to be discovered and characterized. An additional challenge is the counseling and management of children and adults who have a strong family history of cancer yet who do not have a recognizable syndrome. The role of the primary pediatrician is to recognize the major cancer genetic syndromes, to make appropriate referrals for genetic counseling and testing when indicated, and to ensure that adequate

  7. Sources of Error in Mammalian Genetic Screens.

    PubMed

    Sack, Laura Magill; Davoli, Teresa; Xu, Qikai; Li, Mamie Z; Elledge, Stephen J

    2016-09-08

    Genetic screens are invaluable tools for dissection of biological phenomena. Optimization of such screens to enhance discovery of candidate genes and minimize false positives is thus a critical aim. Here, we report several sources of error common to pooled genetic screening techniques used in mammalian cell culture systems, and demonstrate methods to eliminate these errors. We find that reverse transcriptase-mediated recombination during retroviral replication can lead to uncoupling of molecular tags, such as DNA barcodes (BCs), from their associated library elements, leading to chimeric proviral genomes in which BCs are paired to incorrect ORFs, shRNAs, etc This effect depends on the length of homologous sequence between unique elements, and can be minimized with careful vector design. Furthermore, we report that residual plasmid DNA from viral packaging procedures can contaminate transduced cells. These plasmids serve as additional copies of the PCR template during library amplification, resulting in substantial inaccuracies in measurement of initial reference populations for screen normalization. The overabundance of template in some samples causes an imbalance between PCR cycles of contaminated and uncontaminated samples, which results in a systematic artifactual depletion of GC-rich library elements. Elimination of contaminating plasmid DNA using the bacterial endonuclease Benzonase can restore faithful measurements of template abundance and minimize GC bias. Copyright © 2016 Sack et al.

  8. Sources of Error in Mammalian Genetic Screens

    PubMed Central

    Sack, Laura Magill; Davoli, Teresa; Xu, Qikai; Li, Mamie Z.; Elledge, Stephen J.

    2016-01-01

    Genetic screens are invaluable tools for dissection of biological phenomena. Optimization of such screens to enhance discovery of candidate genes and minimize false positives is thus a critical aim. Here, we report several sources of error common to pooled genetic screening techniques used in mammalian cell culture systems, and demonstrate methods to eliminate these errors. We find that reverse transcriptase-mediated recombination during retroviral replication can lead to uncoupling of molecular tags, such as DNA barcodes (BCs), from their associated library elements, leading to chimeric proviral genomes in which BCs are paired to incorrect ORFs, shRNAs, etc. This effect depends on the length of homologous sequence between unique elements, and can be minimized with careful vector design. Furthermore, we report that residual plasmid DNA from viral packaging procedures can contaminate transduced cells. These plasmids serve as additional copies of the PCR template during library amplification, resulting in substantial inaccuracies in measurement of initial reference populations for screen normalization. The overabundance of template in some samples causes an imbalance between PCR cycles of contaminated and uncontaminated samples, which results in a systematic artifactual depletion of GC-rich library elements. Elimination of contaminating plasmid DNA using the bacterial endonuclease Benzonase can restore faithful measurements of template abundance and minimize GC bias. PMID:27402361

  9. Cancer Screening in Older Patients.

    PubMed

    Salzman, Brooke; Beldowski, Kathryn; de la Paz, Amanda

    2016-04-15

    Although cancer is the second leading cause of death among persons 65 years and older, there is a paucity of clinical trial data about the effectiveness and harms of cancer screening in this population. Given the heterogeneous nature of the older population, cancer screening in these patients should not be based on age alone. Studies suggest that a life expectancy of at least 10 years is necessary to derive a survival benefit from screening for breast and colorectal cancers; therefore, screening for these cancers is not recommended in those with a life expectancy of less than 10 years. Prostate cancer screening, if performed at all, should not be performed after 69 years of age. Cervical cancer screening may be stopped after 65 years of age if the patient has an adequate history of negative screening results. An individualized approach to cancer screening decisions involves estimating life expectancy, determining the potential benefits and harms of screenings, and weighing those benefits and harms in relation to the patient's values and preferences.

  10. [Update on preimplantation genetic diagnosis and screening].

    PubMed

    Kőrösi, Tamás; Török, Olga; Vajta, Gábor

    2014-08-31

    Recent advancement in both human embryology and genomics has created a completely new situation for practical and widespread application of preimplantation genetic diagnosis and screening with a dramatic effect on assisted reproduction. The mapping of the first human genome and the advancement in sequencing technology and bioinformatics has led to the discovery of the exact genetic background of exponentially increasing number of diseases. In parallel, methods for culturing human embryos have also radically improved, enabling the late transfer, and the procedure of vitrification the safe cryopreservation. In consequence, refined genetic analyses have become available from blastocyst biopsy followed by the application of novel genomic methods. Furthermore, some studies suggest that by the selection of aneuploid embryos the pregnancy- and birth-rates can be increased. The amount and the depth of information obtainable from the embryos raise several technical and ethical questions that can be answered by further prospective randomized trials.

  11. GAMPMS: Genetic algorithm managed peptide mutant screening.

    PubMed

    Long, Thomas; McDougal, Owen M; Andersen, Tim

    2015-06-30

    The prominence of endogenous peptide ligands targeted to receptors makes peptides with the desired binding activity good molecular scaffolds for drug development. Minor modifications to a peptide's primary sequence can significantly alter its binding properties with a receptor, and screening collections of peptide mutants is a useful technique for probing the receptor-ligand binding domain. Unfortunately, the combinatorial growth of such collections can limit the number of mutations which can be explored using structure-based molecular docking techniques. Genetic algorithm managed peptide mutant screening (GAMPMS) uses a genetic algorithm to conduct a heuristic search of the peptide's mutation space for peptides with optimal binding activity, significantly reducing the computational requirements of the virtual screening. The GAMPMS procedure was implemented and used to explore the binding domain of the nicotinic acetylcholine receptor (nAChR) α3β2-isoform with a library of 64,000 α-conotoxin (α-CTx) MII peptide mutants. To assess GAMPMS's performance, it was compared with a virtual screening procedure that used AutoDock to predict the binding affinity of each of the α-CTx MII peptide mutants with the α3β2-nAChR. The GAMPMS implementation performed AutoDock simulations for as few as 1140 of the 64,000 α-CTx MII peptide mutants and could consistently identify a set of 10 peptides with an aggregated binding energy that was at least 98% of the aggregated binding energy of the 10 top peptides from the exhaustive AutoDock screening.

  12. Cancer Screening and Genetics: A Tale of Two Paradigms

    PubMed Central

    Hamilton, Jada G.; Edwards, Heather M.; Khoury, Muin J.; Taplin, Stephen H.

    2014-01-01

    The long-standing medical tradition to “first do no harm” is reflected in population-wide evidence-based recommendations for cancer screening tests that focus primarily on reducing morbidity and mortality. The conventional cancer screening process is predicated on finding early-stage disease that can be treated effectively; yet emerging genetic and genomic testing technologies have moved the target earlier in the disease development process to identify a probabilistic predisposition to disease. Genetic risk information can have varying implications for the health and well-being of patients and their relatives, and has raised important questions about the evaluation and value of risk information. This paper explores the paradigms that are being applied to the evaluation of conventional cancer screening tests and emerging genetic and genomic tests of cancer susceptibility, and how these perspectives are shifting and evolving in response to advances in our ability to detect cancer risks. We consider several challenges germane to the evaluation of both categories of tests including defining benefits and harms in terms of personal and clinical utility, addressing healthcare consumers’ information preferences, and managing scientific uncertainty. We encourage research and dialogue aimed at developing a better understanding of the value of all risk information, non-genetic and genetic, to people’s lives. PMID:24706727

  13. Coeliac disease and autoimmune disease-genetic overlap and screening.

    PubMed

    Lundin, Knut E A; Wijmenga, Cisca

    2015-09-01

    Coeliac disease is a treatable, gluten-induced disease that often occurs concurrently with other autoimmune diseases. In genetic studies since 2007, a partial genetic overlap between these diseases has been revealed and further insights into the pathophysiology of coeliac disease and autoimmunity have been gained. However, genetic screening is not sensitive and specific enough to accurately predict disease development. The current method to diagnose individuals with coeliac disease is serological testing for the presence of autoantibodies whilst the patient is on a regular, gluten-containing diet, followed by gastroduodenoscopy with duodenal biopsy. Serological test results can also predict the probability of coeliac disease development, even if asymptomatic. In patients with autoimmune diseases known to occur alongside coeliac disease (particularly type 1 diabetes mellitus or thyroid disorders), disease screening-and subsequent treatment if coeliac disease is detected-could have beneficial effects on progression or potential complications of both diseases, owing to the effectiveness of gluten-free dietary interventions in coeliac disease. However, whether diagnosis of coeliac disease and subsequent dietary treatment can prevent autoimmune diseases is debated. In this Review, the genetic and immunological features of coeliac disease, overlap with other autoimmune diseases and implications for current screening strategies will be discussed.

  14. Genetic screening for hypersusceptibles in industry.

    PubMed

    Calabrese, E J

    1981-03-01

    The identification of individuals at increased risk to toxic substances in the workplace has developed into a major issue amongst OSHA, industrial management, and labor. What is needed is the development of a consistent philosophy which is designed to deal with the issues of genetic screening, job placement, and protection of high risk groups with appropriate federal exposure standards. Present evidence does not justify the use of programs designed to identify individuals with hereditary conditions (e.g., G-6-PD deficiency, sickle cell trait) for job denial and/or transfer.

  15. A Genetic Interaction Screen for Breast Cancer Progression Driver Genes

    DTIC Science & Technology

    2013-06-01

    AD_________________ Award Number: W81XWH-12-1-0082 TITLE: A Genetic Interaction Screen for Breast...COVERED 1 2012 - 3 2013 4. TITLE AND SUBTITLE A Genetic Interaction Screen for Breast Cancer Progression Driver Genes 5a. CONTRACT NUMBER...analysis of genetic alterations in human breast cancers has revealed that individual tumors accumulate mutations in approximately ninety different genes

  16. Selection of competent blastocysts for transfer by combining time-lapse monitoring and array CGH testing for patients undergoing preimplantation genetic screening: a prospective study with sibling oocytes

    PubMed Central

    2014-01-01

    Background Recent advances in time-lapse monitoring in IVF treatment have provided new morphokinetic markers for embryonic competence. However, there is still very limited information about the relationship between morphokinetic parameters, chromosomal compositions and implantation potential. Accordingly, this study aimed at investigating the effects of selecting competent blastocysts for transfer by combining time-lapse monitoring and array CGH testing on pregnancy and implantation outcomes for patients undergoing preimplantation genetic screening (PGS). Methods A total of 1163 metaphase II (MII) oocytes were retrieved from 138 PGS patients at a mean age of 36.6 ± 2.4 years. These sibling MII oocytes were then randomized into two groups after ICSI: 1) Group A, oocytes (n = 582) were cultured in the time-lapse system and 2) Group B, oocytes (n = 581) were cultured in the conventional incubator. For both groups, whole genomic amplification and array CGH testing were performed after trophectoderm biopsy on day 5. One to two euploid blastocysts within the most predictive morphokinetic parameters (Group A) or with the best morphological grade available (Group B) were selected for transfer to individual patients on day 6. Ongoing pregnancy and implantation rates were compared between the two groups. Results There were significant differences in clinical pregnancy rates between Group A and Group B (71.1% vs. 45.9%, respectively, p = 0.037). The observed implantation rate per embryo transfer significantly increased in Group A compared to Group B (66.2% vs. 42.4%, respectively, p = 0.011). Moreover, a significant increase in ongoing pregnancy rates was also observed in Group A compared to Group B (68.9% vs. 40.5%. respectively, p = 0.019). However, there was no significant difference in miscarriage rate between the time-lapse system and the conventional incubator (3.1% vs. 11.8%, respectively, p = 0.273). Conclusions This is the first prospective investigation using

  17. Hereditary Colorectal Cancer: Genetics and Screening.

    PubMed

    Brosens, Lodewijk A A; Offerhaus, G Johan A; Giardiello, Francis M

    2015-10-01

    Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in men and women in the United States. About 30% of patients with CRC report a family history of CRC. However, only 5% of CRCs arise in the setting of a well-established mendelian inherited disorder. In addition, serrated polyposis is a clinically defined syndrome with multiple serrated polyps in the colorectum and an increased CRC risk for which the genetics are unknown. This article focuses on genetic and clinical aspects of Lynch syndrome, familial adenomatous polyposis, and MUTYH-associated polyposis. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Hereditary Colorectal Cancer: Genetics and Screening

    PubMed Central

    Offerhaus, G. Johan A.

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in men and women in the United States. Each year more than 140,000 new patients are diagnosed. About 30% of patients with CRC report a family history of CRC. However, only 5% of colorectal cancers arise in the setting of a well-established Mendelian inherited disorder such as Lynch syndrome, familial adenomatous polyposis, MUTYH-associated polyposis, juvenile polyposis, hereditary mixed polyposis, or Peutz-Jeghers. In addition, serrated polyposis is a clinically defined syndrome with multiple serrated polyps in the colorectum and an increased CRC risk for which the genetics are unknown. The majority of familial colorectal cancers arise as so called non-syndromic familial colorectal cancer and likely have a more complex multigenetic cause. This review focuses on genetic and clinical aspects of Lynch syndrome, familial adenomatous polyposis and MUTYH-associated polyposis. PMID:26315524

  19. Genetic screening in adolescents with steroid-resistant nephrotic syndrome.

    PubMed

    Lipska, Beata S; Iatropoulos, Paraskevas; Maranta, Ramona; Caridi, Gianluca; Ozaltin, Fatih; Anarat, Ali; Balat, Ayse; Gellermann, Jutta; Trautmann, Agnes; Erdogan, Ozlem; Saeed, Bassam; Emre, Sevinc; Bogdanovic, Radovan; Azocar, Marta; Balasz-Chmielewska, Irena; Benetti, Elisa; Caliskan, Salim; Mir, Sevgi; Melk, Anette; Ertan, Pelin; Baskin, Esra; Jardim, Helena; Davitaia, Tinatin; Wasilewska, Anna; Drozdz, Dorota; Szczepanska, Maria; Jankauskiene, Augustina; Higuita, Lina Maria Serna; Ardissino, Gianluigi; Ozkaya, Ozan; Kuzma-Mroczkowska, Elzbieta; Soylemezoglu, Oguz; Ranchin, Bruno; Medynska, Anna; Tkaczyk, Marcin; Peco-Antic, Amira; Akil, Ipek; Jarmolinski, Tomasz; Firszt-Adamczyk, Agnieszka; Dusek, Jiri; Simonetti, Giacomo D; Gok, Faysal; Gheissari, Alaleh; Emma, Francesco; Krmar, Rafael T; Fischbach, Michel; Printza, Nikoleta; Simkova, Eva; Mele, Caterina; Ghiggeri, Gian Marco; Schaefer, Franz

    2013-07-01

    Genetic screening paradigms for congenital and infantile nephrotic syndrome are well established; however, screening in adolescents has received only minor attention. To help rectify this, we analyzed an unselected adolescent cohort of the international PodoNet registry to develop a rational screening approach based on 227 patients with nonsyndromic steroid-resistant nephrotic syndrome aged 10-20 years. Of these, 21% had a positive family history. Autosomal dominant cases were screened for WT1, TRPC6, ACTN4, and INF2 mutations. All other patients had the NPHS2 gene screened, and WT1 was tested in sporadic cases. In addition, 40 sporadic cases had the entire coding region of INF2 tested. Of the autosomal recessive and the sporadic cases, 13 and 6%, respectively, were found to have podocin-associated nephrotic syndrome, and 56% of them were compound heterozygous for the nonneutral p.R229Q polymorphism. Four percent of the sporadic and 10% of the autosomal dominant cases had a mutation in WT1. Pathogenic INF2 mutations were found in 20% of the dominant but none of the sporadic cases. In a large cohort of adolescents including both familial and sporadic disease, NPHS2 mutations explained about 7% and WT1 4% of cases, whereas INF2 proved relevant only in autosomal dominant familial disease. Thus, screening of the entire coding sequence of NPHS2 and exons 8-9 of WT1 appears to be the most rational and cost-effective screening approach in sporadic juvenile steroid-resistant nephrotic syndrome.

  20. The art and design of genetic screens: maize

    USDA-ARS?s Scientific Manuscript database

    Maize (Zea mays) is an excellent model for basic research. Genetic screens have informed our understanding of developmental processes, meiosis, epigenetics and biochemical pathways--not only in maize but also in other cereal crops. We discuss the forward and reverse genetic screens that are possible...

  1. A Chemical Genetic Screening Procedure for Arabidopsis thaliana Seedlings

    PubMed Central

    Bjornson, Marta; Song, Xingshun; Dandekar, Abhaya; Franz, Annaliese; Drakakaki, Georgia; Dehesh, Katayoon

    2016-01-01

    Unbiased screening approaches are powerful tools enabling identification of novel players in biological processes. Chemical genetic screening refers to the technique of using a reporter response, such as expression of luciferase driven by a promoter of interest, to discover small molecules that affect a given process when applied to plants. These chemicals then act as tools for identification of regulatory components that could not otherwise be detected by forward genetic screens due to gene family redundancy or mutant lethality. This protocol describes a chemical genetic screen using Arabidopsis thaliana seedlings, which has led to recognition of novel players in the plant general stress response. PMID:27446980

  2. Moving up the slippery slope: mandated genetic screening on Cyprus.

    PubMed

    Cowan, Ruth Schwartz

    2009-02-15

    Many social scientists and bioethicists have argued that genetic screening is a new form of eugenics. Examination of the development of the quasi-mandated screening program for beta-thalassemia in the Republic of Cyprus (1970-1984) demonstrates that there is nothing eugenic about modern genetic screening practices. The Cypriot screening program involves mandated premarital carrier screening, voluntary prenatal diagnosis (originally through fetoscopy, now through CVS), and voluntary termination of afflicted pregnancies-all at public expense. In the Republic of Cyprus, the mandating agency for genetic screening is the established church, so this examination also demonstrates that religious authorities with profound objections to abortion can balance that moral precept against others, such as the imperative to reduce suffering that sometimes conflict with it. (c) 2009 Wiley-Liss, Inc.

  3. The art and design of genetic screens: maize.

    PubMed

    Candela, Héctor; Hake, Sarah

    2008-03-01

    Maize (Zea mays) is an excellent model for basic research. Genetic screens have informed our understanding of developmental processes, meiosis, epigenetics and biochemical pathways--not only in maize but also in other cereal crops. We discuss the forward and reverse genetic screens that are possible in this organism, and emphasize the available tools. Screens exploit the well-studied behaviour of transposon systems, and the distinctive chromosomes allow an integration of cytogenetics into mutagenesis screens and analyses. The imminent completion of the maize genome sequence provides the essential resource to move seamlessly from gene to phenotype and back.

  4. Two pediatric patients with Von Hippel-Lindau disease type 2b: from patient to screening, from screening to patient.

    PubMed

    Gonc, Nazli; Engiz, Ozlem; Neumann, Hartmut P H; Demirbilek, Huseyin; Ozon, Alev; Alikasifoglu, Ayfer; Kandemir, Nurgun

    2011-01-01

    Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited tumor susceptibility disease characterized by the development of hemangioblastomas of the brain, spinal cord and retina; pheochromocytomas and renal cell carcinoma. The disease is caused by mutations in the VHL tumor suppressor gene located on chromosome 3p26-p25. In this paper, we present two patients with VHL disease type 2B confirmed by genetic analysis. Diagnosis in the first patient was based on demonstration of retinal hemangioblastoma in association with bilateral pheochromocytoma. Family screening revealed renal cell carcinoma in her father and uncle. The second patient was discovered during family screening of another index case in adult age. VHL disease should be clinically suspected in any individual with a pheochromocytoma especially when there is bilateral and/or multifocal disease or family history. Screening of patients and at-risk family members for VHL-associated tumors should be essential in management of VHL.

  5. Compliance for genetic screening in the Arab population in Israel.

    PubMed

    Sukenik-Halevy, Rivka; Leil-Zoabi, Ulfat Abu; Peled-Perez, Lilach; Zlotogora, Joel; Allon-Shalev, Stavit

    2012-09-01

    Genetic screening tests for cystic fibrosis (CF), fragile X (FRAX) and spinal muscular atrophy (SMA) have been offered to the entire Arab population of Israel in the last few years. Since 2008, screening for CF is provided free of charge, but for FRAX and SMA the screening is privately funded with partial coverage by complementary health insurance programs. To assess the compliance of Arab couples with regard to genetic screening tests, and the factors that affect their decisions. We analyzed compliance for genetic screening tests at the Emek Medical Center Genetic Institute, and in outreach clinics in four Arab villages. We enquired about the reasons individuals gave for deciding not to undergo testing. We also assessed the compliance of these individuals for the triple test (a screening test for Down syndrome). Of the 167 individuals included in our study, 24 (14%) decided not to be tested at all. Of the 143 (86%) who decided to be tested, 109 were tested for CF only (65%) and 34 (20%) for SMA and FRAX (as well as CF). The compliance rate for the triple test was 87%. Technical reasons, mainly financial issues, were the most significant factor for not undergoing all three tests. The compliance of the Arab community for genetic testing for SMA and FRAX is extremely low. We believe that this low utilization of screening is due to economic reasons, especiallywhen a complementary health plan has not been acquired, and largely reflects the perception that these tests are less important since they are privately funded.

  6. Genetic Screening of Cells with Enhanced Antibody Production

    DTIC Science & Technology

    2007-01-22

    Final Progress Report DARPA Grant No. W911NF-05-C-0059 Genetic Screening of Cells with Enhanced Antibody Production By Roxanne Duan, Ph.D...Functional Genetics , Inc. January 22, 2007 Summary Here we report the progress made for grant No. W911NF-05-C-0059 between the entire funding...period, 06/01/05 and 8/31/06. We have completed the study proposed: to use Functional Genetics ’ proprietary technology, Random Homozygous Knock Out

  7. The art and design of genetic screens: mouse.

    PubMed

    Kile, Benjamin T; Hilton, Douglas J

    2005-07-01

    Humans are mammals, not bacteria or plants, yeast or nematodes, insects or fish. Mice are also mammals, but unlike gorilla and goat, fox and ferret, giraffe and jackal, they are suited perfectly to the laboratory environment and genetic experimentation. In this review, we will summarize the tools, tricks and techniques for executing forward genetic screens in the mouse and argue that this approach is now accessible to most biologists, rather than being the sole domain of large national facilities and specialized genetics laboratories.

  8. The Cost-effectiveness of Genetic Screening for Familial Hypercholesterolemia: a Systematic Review.

    PubMed

    Rosso, A; Pitini, E; D'Andrea, E; Massimi, A; De Vito, C; Marzuillo, C; Villari, P

    2017-01-01

    Familial hypercholesterolemia (FH) is a genetic disorder that leads to elevated plasma LDL-cholesterol levels and premature coronary heart disease (CHD). An understanding of the mutations responsible for FH and the effectiveness of statins in lowering the risk of CHD in FH patients has increased interest in genetic screening strategies to improve FH diagnosis. In this study, we aimed to evaluate the cost-effectiveness of such strategies. We performed a systematic review of full economic evaluations that assessed the cost-effectiveness of FH genetic screening strategies. We used relevant search terms to investigate Medline, Scopus, Web of Science, the Database of Abstracts of Reviews of Effects, the Health Technology Assessment Database, and the National Health Service Economic Evaluation Database. Data extraction and assessment of the quality of the studies were performed independently by two reviewers. The key features of the included studies are summarized in a narrative synthesis. We included seven economic evaluations that assessed the cost-effectiveness of genetic screening for FH, published mainly in Europe between 2002 and 2015. Most studies had a no-screening strategy as a comparator, focused on relatives of index cases with genetic or clinical diagnosis of FH (cascade screening), considered a lifetime horizon and adopted a health care payer viewpoint. Cascade screening, based on genetic testing of relatives of an index case with confirmed clinical or genetic diagnosis of FH, was shown to be cost-effective in most settings. Our review confirms the cost-effectiveness of cascade genetic screening for the diagnosis of FH. Further research may be needed to assess the cost-effectiveness of cascade screening following the introduction of newly recommended therapeutic regimes and next-generation sequencing.

  9. Screening Jews and genes: a consideration of the ethics of genetic screening within the Jewish community: challenges and responses.

    PubMed

    Levin, M

    1999-01-01

    Screening for genetic disorders, particularly Tay-Sachs Disease, has been traditionally welcome by the Jewish community. I review the history of genetic screening among Jews and the views from the Jewish tradition on the subject, and then discuss ethical challenges of screening and the impact of historical memories upon future acceptance of screening programs. Some rational principles to guide future design of genetic screening programs among Jews are proposed.

  10. Motherhood and Genetic Screening: A Personal Perspective

    ERIC Educational Resources Information Center

    Place, Fiona

    2008-01-01

    According to the medical profession the direction and scope of reproductive services such as IVF and pre-natal screening are based on solid evidence; the evidence indicates these are effective and safe services. Moreover, women want them. As a consequence these services are usually presented to the wider community in a positive light with images…

  11. Motherhood and Genetic Screening: A Personal Perspective

    ERIC Educational Resources Information Center

    Place, Fiona

    2008-01-01

    According to the medical profession the direction and scope of reproductive services such as IVF and pre-natal screening are based on solid evidence; the evidence indicates these are effective and safe services. Moreover, women want them. As a consequence these services are usually presented to the wider community in a positive light with images…

  12. Genetic Screen for PTSD-Prone Soldiers

    DTIC Science & Technology

    2009-08-01

    for determining genotypes at 8 loci in the calcyon gene which is strongly associated with attention deficit hyperactivity disorder (ADHD) and...associated with attention deficit hyperactivity disorder (ADHD) could be useful as an unbiased screen for PTSD-prone soldiers. Subjects participating... deficit / hyperactivity disorder . Mol. Psychiatry 10, 1117-1125. Li,J.Z., Absher,D.M., Tang,H., Southwick,A.M., Casto,A.M., Ramachandran,S., Cann,H.M

  13. Genetic Screening: A Unique Game of Survival

    ERIC Educational Resources Information Center

    Kurvink, Karen; Bowser, Jessica

    2004-01-01

    A creative learning game that helps students reinforce basic genetic information and facilitate the identification and understanding of the more subtle issues is presented. The basic framework of the game was conceived by a business major taking non-biology major course 'heredity and society-intertwining legacy.

  14. Genetic Screening: A Unique Game of Survival

    ERIC Educational Resources Information Center

    Kurvink, Karen; Bowser, Jessica

    2004-01-01

    A creative learning game that helps students reinforce basic genetic information and facilitate the identification and understanding of the more subtle issues is presented. The basic framework of the game was conceived by a business major taking non-biology major course 'heredity and society-intertwining legacy.

  15. Genetic screening and diagnosis in epilepsy?

    PubMed

    Sisodiya, Sanjay M

    2015-04-01

    Genetic discovery has been extremely rapid over the last year, with many new discoveries illuminating novel mechanisms and pathways. In particular, the application of whole exome and whole genome sequencing has identified many new genetic causes of the epilepsies. As such methods become increasingly available, it will be critical for practicing neurologists to be acquainted with them. This review surveys some important developments over the last year. The range of tests available to the clinician is wide, and likely soon to be dominated by whole exome and whole genome sequencing. Both whole exome and whole genome sequencing have usually proven to be more powerful than most existing tests. Many new genes have been implicated in the epilepsies, with emerging evidence of the involvement of particular multigene pathways. For the practicing clinician, it will be important to appreciate progress in the field, and to prepare for the application of novel genetic testing in clinical practice, as genetic data are likely to contribute importantly for many people with epilepsy.

  16. Preimplantation genetic diagnosis and screening by array comparative genomic hybridisation: experience of more than 100 cases in a single centre.

    PubMed

    Chow, J Fc; Yeung, W Sb; Lee, V Cy; Lau, E Yl; Ho, P C; Ng, E Hy

    2017-04-01

    Preimplantation genetic screening has been proposed to improve the in-vitro fertilisation outcome by screening for aneuploid embryos or blastocysts. This study aimed to report the outcome of 133 cycles of preimplantation genetic diagnosis and screening by array comparative genomic hybridisation. This study of case series was conducted in a tertiary assisted reproductive centre in Hong Kong. Patients who underwent preimplantation genetic diagnosis for chromosomal abnormalities or preimplantation genetic screening between 1 April 2012 and 30 June 2015 were included. They underwent in-vitro fertilisation and intracytoplasmic sperm injection. An embryo biopsy was performed on day-3 embryos and the blastomere was subject to array comparative genomic hybridisation. Embryos with normal copy numbers were replaced. The ongoing pregnancy rate, implantation rate, and miscarriage rate were studied. During the study period, 133 cycles of preimplantation genetic diagnosis for chromosomal abnormalities or preimplantation genetic screening were initiated in 94 patients. Overall, 112 cycles proceeded to embryo biopsy and 65 cycles had embryo transfer. The ongoing pregnancy rate per transfer cycle after preimplantation genetic screening was 50.0% and that after preimplantation genetic diagnosis was 34.9%. The implantation rates after preimplantation genetic screening and diagnosis were 45.7% and 41.1%, respectively and the miscarriage rates were 8.3% and 28.6%, respectively. There were 26 frozen-thawed embryo transfer cycles, in which vitrified and biopsied genetically transferrable embryos were replaced, resulting in an ongoing pregnancy rate of 36.4% in the screening group and 60.0% in the diagnosis group. The clinical outcomes of preimplantation genetic diagnosis and screening using comparative genomic hybridisation in our unit were comparable to those reported internationally. Genetically transferrable embryos replaced in a natural cycle may improve the ongoing pregnancy rate

  17. Maximising the efficiency of clinical screening programmes: balancing predictive genetic testing with a right not to know

    PubMed Central

    Schuurman, Agnes G; van der Kolk, Dorina M; Verkerk, Marian A; Birnie, Erwin; Ranchor, Adelita V; Plantinga, Mirjam; van Langen, Irene M

    2015-01-01

    We explored the dilemma between patients' right not to know their genetic status and the efficient use of health-care resources in the form of clinical cancer screening programmes. Currently, in the Netherlands, 50% risk carriers of heritable cancer syndromes who choose not to know their genetic status have access to the same screening programmes as proven mutation carriers. This implies an inefficient use of health-care resources, because half of this group will not carry the familial mutation. At the moment, only a small number of patients are involved; however, the expanding possibilities for genetic risk profiling means this issue must be addressed because of potentially adverse societal and financial impact. The trade-off between patients' right not to know their genetic status and efficient use of health-care resources was discussed in six focus groups with health-care professionals and patients from three Dutch university hospitals. Professionals prefer patients to undergo a predictive DNA test as a prerequisite for entering cancer screening programmes. Professionals prioritise treating sick patients or proven mutation carriers over screening untested individuals. Participation in cancer screening programmes without prior DNA testing is, however, supported by most professionals, as testing is usually delayed and relatively few patients are involved at present. Reducing the number of 50% risk carriers undergoing screening is expected to be achieved by: offering more psychosocial support, explaining the iatrogenic risks of cancer screening, increasing out-of-pocket costs, and offering a less stringent screening programme for 50% risk carriers. PMID:25564039

  18. Maximising the efficiency of clinical screening programmes: balancing predictive genetic testing with a right not to know.

    PubMed

    Schuurman, Agnes G; van der Kolk, Dorina M; Verkerk, Marian A; Birnie, Erwin; Ranchor, Adelita V; Plantinga, Mirjam; van Langen, Irene M

    2015-09-01

    We explored the dilemma between patients' right not to know their genetic status and the efficient use of health-care resources in the form of clinical cancer screening programmes. Currently, in the Netherlands, 50% risk carriers of heritable cancer syndromes who choose not to know their genetic status have access to the same screening programmes as proven mutation carriers. This implies an inefficient use of health-care resources, because half of this group will not carry the familial mutation. At the moment, only a small number of patients are involved; however, the expanding possibilities for genetic risk profiling means this issue must be addressed because of potentially adverse societal and financial impact. The trade-off between patients' right not to know their genetic status and efficient use of health-care resources was discussed in six focus groups with health-care professionals and patients from three Dutch university hospitals. Professionals prefer patients to undergo a predictive DNA test as a prerequisite for entering cancer screening programmes. Professionals prioritise treating sick patients or proven mutation carriers over screening untested individuals. Participation in cancer screening programmes without prior DNA testing is, however, supported by most professionals, as testing is usually delayed and relatively few patients are involved at present. Reducing the number of 50% risk carriers undergoing screening is expected to be achieved by: offering more psychosocial support, explaining the iatrogenic risks of cancer screening, increasing out-of-pocket costs, and offering a less stringent screening programme for 50% risk carriers.

  19. Impact of preimplantation genetic screening on donor oocyte-recipient cycles in the United States.

    PubMed

    Barad, David H; Darmon, Sarah K; Kushnir, Vitaly A; Albertini, David F; Gleicher, Norbert

    2017-07-20

    Our objective was to estimate the contribution of preimplantation genetic screening to in vitro fertilization pregnancy outcomes in donor oocyte-recipient cycles. This was a retrospective cross-sectional study of US national data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System between 2005 and 2013. Society for Assisted Reproductive Technology Clinic Outcome Reporting relies on voluntarily annual reports by more than 90% of US in vitro fertilization centers. We evaluated pregnancy and live birth rates in donor oocyte-recipient cycles after the first embryo transfer with day 5/6 embryos. Statistical models, adjusted for patient and donor ages, number of embryos transferred, race, infertility diagnosis, and cycle year were created to compare live birth rates in 392 preimplantation genetic screening and 20,616 control cycles. Overall, pregnancy and live birth rates were significantly lower in preimplantation genetic screening cycles than in control cycles. Adjusted odds of live birth for preimplantation genetic screening cycles were reduced by 35% (odds ratio, 0.65, 95% confidence interval, 0.53-0.80; P < .001). Preimplantation genetic screening, as practiced in donor oocyte-recipient cycles over the past 9 years, has not been associated with improved odds of live birth or reduction in miscarriage rates. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Patient Beliefs About Colon Cancer Screening.

    PubMed

    Ely, John W; Levy, Barcey T; Daly, Jeanette; Xu, Yinghui

    2016-03-01

    Only about half of eligible individuals undergo colon cancer screening. We have limited knowledge about the patient beliefs that adversely affect screening decisions and about which beliefs might be amenable to change through education. As part of a clinical trial, 641 rural Iowans, aged 52 to 79 years, reported their beliefs about colon cancer screening in response to a mailed questionnaire. Consenting subjects were randomized into four groups, which were distinguished by four levels of increasingly intensive efforts to promote screening. Two of the groups received mailed educational materials and completed a follow-up questionnaire, which allowed us to determine whether their beliefs about screening changed following the education. We also completed a factor analysis to identify underlying (latent) factors that might explain the responses to 33 questions about readiness, attitudes, and perceived barriers related to colon cancer screening. The strongest predictors of a patient's stated readiness to be screened were a physician's recommendation to be screened (1 point difference on 10-point Likert scale, 95 % confidence interval [CI], 0.5 to 1.6 point difference), a family history of colon cancer (0.85-point Likert scale difference, 95 % CI, 0.1 to 1.6), and a belief that health-care decisions should be mostly left to physicians rather than patients (Spearman correlation coefficient 0.21, P < .001). Of the 33 questionnaire items about screening beliefs, 11 (33 %) changed favorably following the educational intervention. In the factor analysis, the 33 items were reduced to 8 underlying factors, such as being too busy to undergo screening and worries about screening procedures. We found a limited number of underlying factors that may help explain patient resistance to colon cancer screening.

  1. Coupled mutagenesis screens and genetic mapping in zebrafish.

    PubMed Central

    Rawls, John F; Frieda, Matthew R; McAdow, Anthony R; Gross, Jason P; Clayton, Chad M; Heyen, Candy K; Johnson, Stephen L

    2003-01-01

    Forward genetic analysis is one of the principal advantages of the zebrafish model system. However, managing zebrafish mutant lines derived from mutagenesis screens and mapping the corresponding mutations and integrating them into the larger collection of mutations remain arduous tasks. To simplify and focus these endeavors, we developed an approach that facilitates the rapid mapping of new zebrafish mutations as they are generated through mutagenesis screens. We selected a minimal panel of 149 simple sequence length polymorphism markers for a first-pass genome scan in crosses involving C32 and SJD inbred lines. We also conducted a small chemical mutagenesis screen that identified several new mutations affecting zebrafish embryonic melanocyte development. Using our first-pass marker panel in bulked-segregant analysis, we were able to identify the genetic map positions of these mutations as they were isolated in our screen. Rapid mapping of the mutations facilitated stock management, helped direct allelism tests, and should accelerate identification of the affected genes. These results demonstrate the efficacy of coupling mutagenesis screens with genetic mapping. PMID:12663538

  2. Evaluation of newborn screening bloodspot-based genetic testing as second tier screen for bedside newborn hearing screening.

    PubMed

    Schimmenti, Lisa A; Warman, Berta; Schleiss, Mark R; Daly, Kathleen A; Ross, Julie A; McCann, Mark; Jurek, Anne M; Berry, Susan A

    2011-12-01

    : Bedside newborn hearing screening is highly successful in identifying deaf or hard-of-hearing infants. However, newborn hearing screening protocols have high loss to follow-up rates. We propose that bloodspot-based genetic testing for GJB2 alleles can provide a means for rapid confirmation in a subset of infants who fail bedside newborn hearing screening. : We performed a case-control study comparing the prevalence of common GJB2 mutations from deidentified bloodspots designated as "refer" by newborn hearing screening and contemporaneously selected randomly chosen controls designated as "pass." Between March 2006 and December 2007, 2354 spots were analyzed for common alleles, c.35delG, c.167delT, c.235delC, and p.V37I in GJB2 with a subset reanalyzed by conventional Sanger sequencing to search for additional alleles. : The prevalence of biallelic GJB2 mutations in bloodspots from infants who referred by newborn hearing screening is approximately 1 in 50 (23/1177). In contrast, one bloodspot from an infant who passed newborn hearing screening was identified to harbor biallelic GJB2 mutations. : These findings show that when a newborn refers by newborn hearing screening, there is a significant chance that GJB2-related hearing loss is present. Bloodspot-based genetic testing for common GJB2 alleles should be considered as second tier testing for bedside newborn hearing screening.

  3. Should patients with ocular genetic disorders have genetic testing?

    PubMed

    Zanolli, Mario T; Khetan, Vikas; Dotan, Gad; Pizzi, Laura; Levin, Alex V

    2014-09-01

    To discuss the risks, benefits and value of genetic testing for ocular genetic disease. Testing for ocular genetics diseases is becoming more available and successful gene therapy is being reported. Clinicians must prepare for this trend by considering diagnostic genetic testing for their patients. As advances continually occur in genetic testing for ocular genetic disorders, clinicians must develop an understanding of the potential risks and benefits for their patients.

  4. Motherhood and genetic screening: a personal perspective.

    PubMed

    Place, Fiona

    2008-10-01

    According to the medical profession the direction and scope of reproductive services such as IVF and pre-natal screening are based on solid evidence; the evidence indicates these are effective and safe services. Moreover, women want them. As a consequence these services are usually presented to the wider community in a positive light with images of 'successful' birth outcomes showcasing the importance of their work. Unsurprisingly this has lead to women being expected to take control - from timing a pregnancy to choosing one particular pregnancy over another - they are to improve their lives and the health of their offspring. But are these developments all 'good' news? Is it safe to assume the push to achieve better birth outcomes and the concomitant use of prenatal testing automatically improves lives? Could it be the issues raised are causing some lives to become harder? How meaningful, for example, are tests such as amniocentesis and CVS? As the mother of a child with Down syndrome I believe it is important for myself and other women in similar situations to share their lived experience. Perhaps we can illuminate some of the more complex and troubling issues these technological advances have the capacity to create - not only for ourselves - but for all women.

  5. Genetic signature of histiocytic sarcoma revealed by a sleeping beauty transposon genetic screen in mice.

    PubMed

    Been, Raha A; Linden, Michael A; Hager, Courtney J; DeCoursin, Krista J; Abrahante, Juan E; Landman, Sean R; Steinbach, Michael; Sarver, Aaron L; Largaespada, David A; Starr, Timothy K

    2014-01-01

    Histiocytic sarcoma is a rare, aggressive neoplasm that responds poorly to therapy. Histiocytic sarcoma is thought to arise from macrophage precursor cells via genetic changes that are largely undefined. To improve our understanding of the etiology of histiocytic sarcoma we conducted a forward genetic screen in mice using the Sleeping Beauty transposon as a mutagen to identify genetic drivers of histiocytic sarcoma. Sleeping Beauty mutagenesis was targeted to myeloid lineage cells using the Lysozyme2 promoter. Mice with activated Sleeping Beauty mutagenesis had significantly shortened lifespan and the majority of these mice developed tumors resembling human histiocytic sarcoma. Analysis of transposon insertions identified 27 common insertion sites containing 28 candidate cancer genes. Several of these genes are known drivers of hematological neoplasms, like Raf1, Fli1, and Mitf, while others are well-known cancer genes, including Nf1, Myc, Jak2, and Pten. Importantly, several new potential drivers of histiocytic sarcoma were identified and could serve as targets for therapy for histiocytic sarcoma patients.

  6. Genetic Signature of Histiocytic Sarcoma Revealed by a Sleeping Beauty Transposon Genetic Screen in Mice

    PubMed Central

    Been, Raha A.; Linden, Michael A.; Hager, Courtney J.; DeCoursin, Krista J.; Abrahante, Juan E.; Landman, Sean R.; Steinbach, Michael; Sarver, Aaron L.; Largaespada, David A.; Starr, Timothy K.

    2014-01-01

    Histiocytic sarcoma is a rare, aggressive neoplasm that responds poorly to therapy. Histiocytic sarcoma is thought to arise from macrophage precursor cells via genetic changes that are largely undefined. To improve our understanding of the etiology of histiocytic sarcoma we conducted a forward genetic screen in mice using the Sleeping Beauty transposon as a mutagen to identify genetic drivers of histiocytic sarcoma. Sleeping Beauty mutagenesis was targeted to myeloid lineage cells using the Lysozyme2 promoter. Mice with activated Sleeping Beauty mutagenesis had significantly shortened lifespan and the majority of these mice developed tumors resembling human histiocytic sarcoma. Analysis of transposon insertions identified 27 common insertion sites containing 28 candidate cancer genes. Several of these genes are known drivers of hematological neoplasms, like Raf1, Fli1, and Mitf, while others are well-known cancer genes, including Nf1, Myc, Jak2, and Pten. Importantly, several new potential drivers of histiocytic sarcoma were identified and could serve as targets for therapy for histiocytic sarcoma patients. PMID:24827933

  7. Genetic dissection of mammalian ERAD through comparative haploid and CRISPR forward genetic screens

    PubMed Central

    Timms, Richard T.; Menzies, Sam A.; Tchasovnikarova, Iva A.; Christensen, Lea C.; Williamson, James C.; Antrobus, Robin; Dougan, Gordon; Ellgaard, Lars; Lehner, Paul J.

    2016-01-01

    The application of forward genetic screens to cultured human cells represents a powerful method to study gene function. The repurposing of the bacterial CRISPR/Cas9 system provides an effective method to disrupt gene function in mammalian cells, and has been applied to genome-wide screens. Here, we compare the efficacy of genome-wide CRISPR/Cas9-mediated forward genetic screens versus gene-trap mutagenesis screens in haploid human cells, which represent the existing ‘gold standard' method. This head-to-head comparison aimed to identify genes required for the endoplasmic reticulum-associated degradation (ERAD) of MHC class I molecules. The two approaches show high concordance (>70%), successfully identifying the majority of the known components of the canonical glycoprotein ERAD pathway. Both screens also identify a role for the uncharacterized gene TXNDC11, which we show encodes an EDEM2/3-associated disulphide reductase. Genome-wide CRISPR/Cas9-mediated screens together with haploid genetic screens provide a powerful addition to the forward genetic toolbox. PMID:27283361

  8. Multi-enzyme Screening Using a High-throughput Genetic Enzyme Screening System.

    PubMed

    Kim, Haseong; Kwon, Kil Koang; Seong, Wonjae; Lee, Seung-Goo

    2016-08-08

    The recent development of a high-throughput single-cell assay technique enables the screening of novel enzymes based on functional activities from a large-scale metagenomic library(1). We previously proposed a genetic enzyme screening system (GESS) that uses dimethylphenol regulator activated by phenol or p-nitrophenol. Since a vast amount of natural enzymatic reactions produce these phenolic compounds from phenol deriving substrates, this single genetic screening system can be theoretically applied to screen over 200 different enzymes in the BRENDA database. Despite the general applicability of GESS, applying the screening process requires a specific procedure to reach the maximum flow cytometry signals. Here, we detail the developed screening process, which includes metagenome preprocessing with GESS and the operation of a flow cytometry sorter. Three different phenolic substrates (p-nitrophenyl acetate, p-nitrophenyl-β-D-cellobioside, and phenyl phosphate) with GESS were used to screen and to identify three different enzymes (lipase, cellulase, and alkaline phosphatase), respectively. The selected metagenomic enzyme activities were confirmed only with the flow cytometry but DNA sequencing and diverse in vitro analysis can be used for further gene identification.

  9. Evaluation of two-year Jewish genetic disease screening program in Atlanta: insight into community genetic screening approaches.

    PubMed

    Shao, Yunru; Liu, Shuling; Grinzaid, Karen

    2015-04-01

    Improvements in genetic testing technologies have led to the development of expanded carrier screening panels for the Ashkenazi Jewish population; however, there are major inconsistencies in current screening practices. A 2-year pilot program was launched in Atlanta in 2010 to promote and facilitate screening for 19 Jewish genetic diseases. We analyzed data from this program, including participant demographics and outreach efforts. This retrospective analysis is based on a de-identified dataset of 724 screenees. Data were obtained through medical chart review and questionnaires and included demographic information, screening results, response to outreach efforts, and follow-up behavior and preferences. We applied descriptive analysis, chi-square tests, and logistic regression to analyze the data and compare findings with published literature. The majority of participants indicated that they were not pregnant or did not have a partner who was pregnant were affiliated with Jewish organizations and reported 100 % AJ ancestry. Overall, carrier frequency was 1 in 3.9. Friends, rabbis, and family members were the most common influencers of the decision to receive screening. People who were older, had a history of pregnancy, and had been previously screened were more likely to educate others (all p < 0.05). Analysis of this 2-year program indicated that people who are ready to have children or expand their families are more likely to get screened and encourage others to be screened. The most effective outreach efforts targeted influencers who then encouraged screening in the target population. Educating influencers and increasing overall awareness were the most effective outreach strategies.

  10. Cancer Screening Among Patients With Advanced Cancer

    PubMed Central

    Sima, Camelia S.; Panageas, Katherine S.; Schrag, Deborah

    2013-01-01

    Context Cancer screening has been integrated into routine primary care but does not benefit patients with limited life expectancy. Objective To evaluate the extent to which patients with advanced cancer continue to be screened for new cancers. Design, Setting, and Participants Utilization of cancer screening procedures (mammography, Papanicolaou test, prostate-specific antigen [PSA], and lower gastrointestinal [GI] endoscopy) was assessed in 87 736 fee-for-service Medicare enrollees aged 65 years or older diagnosed with advanced lung, colorectal, pancreatic, gastroesophageal, or breast cancer between 1998 and 2005, and reported to one of the Surveillance, Epidemiology, and End Results (SEER) tumor registries. Participants were followed up until death or December 31, 2007, whichever came first. A group of 87 307 Medicare enrollees without cancer were individually matched by age, sex, race, and SEER registry to patients with cancer and observed over the same period to evaluate screening rates in context. Demographic and clinical characteristics associated with screening were also investigated. Main Outcome Measure For each cancer screening test, utilization rates were defined as the percentage of patients who were screened following the diagnosis of an incurable cancer. Results Among women following advanced cancer diagnosis compared with controls, at least 1 screening mammogram was received by 8.9% (95% confidence interval [CI], 8.6%-9.1%) vs 22.0% (95% CI, 21.7%-22.5%); Papanicolaou test screening was received by 5.8% (95% CI, 5.6%-6.1%) vs 12.5% (95% CI, 12.2%-12.8%). Among men following advanced cancer diagnosis compared with controls, PSA test was received by 15.0% (95% CI, 14.7%-15.3%) vs 27.2% (95% CI, 26.8%-27.6%). For all patients following advanced diagnosis compared with controls, lower GI endoscopy was received by 1.7% (95% CI, 1.6%-1.8%) vs 4.7% (95% CI, 4.6%-4.9%). Screening was more frequent among patients with a recent history of screening (16.2% [95

  11. Genetic screening with the DNA chip: a new Pandora's box?

    PubMed Central

    Henn, W

    1999-01-01

    The ethically controversial option of genetic population screening used to be restricted to a small number of rather rare diseases by methodological limitations which are now about to be overcome. With the new technology of DNA microarrays ("DNA chip"), emerging from the synthesis of microelectronics and molecular biology, methods are now at hand for the development of mass screening programmes for a wide spectrum of genetic traits. Thus, the DNA chip may be the key technology for a refined preventive medicine as well as a new dimension of eugenics. The forthcoming introduction of the DNA chip technology into medical practice urgently requires an internationally consistent framework of ethical standards and legal limitations if we do not want it to become a new Pandora's box. PMID:10226928

  12. Genetic Screens in Yeast to Identify BRCA1 Modifiers

    DTIC Science & Technology

    2005-12-01

    EUG1 YDR518W protein folding FLO9 YAL063C inv in flocculation FOB1 YDR110W,HRM1 DNA replication fork blocking GCR1 YPL075W transcriptional activator... initiated . The PI of this proposal is participating in a multi-institutional study through the Cancer Genetics Network to collect DNA samples and...insertional mutagenesis screen using Synder Library DNA into strains developed in Tasks 1 and 2. a. Assay for changes in chromosome loss rate. Progress

  13. Genetic screening as a technique of government: the case of neonatal screening for cystic fibrosis in France.

    PubMed

    Vailly, Joëlle

    2006-12-01

    The biomedicalization process and the rise of genetics that have occurred in the last few decades raise political issues concerning the ability of subjects in biomedicine to act and make choices. My work examines these issues through a study of the process by which neonatal screening for the genetic disease of cystic fibrosis (CF) was set up in France. It draws on qualitative interviews with 25 national officials making use of the Foucauldian notion of government, which implies power relations among entities recognized as subjects of action. I examine how different agents (or groups) came to form either governing or governable entities within this health policy, and by what means governance in this area is exercised. The study positions relations between governors and the governed in the dynamics specific to them, showing that screening for CF is, to a large degree, a political technique for governing self and others based on a biomedical technique. Two types of subject (a professionals' association and a patients' association) are seen to be constituted in different ways and endowed with more or less extensive power. More generally, the study raises the question of the form of the political, through the example of genetic screening.

  14. Forward genetic screen for auxin-deficient mutants by cytokinin.

    PubMed

    Wu, Lei; Luo, Pan; Di, Dong-Wei; Wang, Li; Wang, Ming; Lu, Cheng-Kai; Wei, Shao-Dong; Zhang, Li; Zhang, Tian-Zi; Amakorová, Petra; Strnad, Miroslav; Novák, Ondřej; Guo, Guang-Qin

    2015-07-06

    Identification of mutants with impairments in auxin biosynthesis and dynamics by forward genetic screening is hindered by the complexity, redundancy and necessity of the pathways involved. Furthermore, although a few auxin-deficient mutants have been recently identified by screening for altered responses to shade, ethylene, N-1-naphthylphthalamic acid (NPA) or cytokinin (CK), there is still a lack of robust markers for systematically isolating such mutants. We hypothesized that a potentially suitable phenotypic marker is root curling induced by CK, as observed in the auxin biosynthesis mutant CK-induced root curling 1 / tryptophan aminotransferase of Arabidopsis 1 (ckrc1/taa1). Phenotypic observations, genetic analyses and biochemical complementation tests of Arabidopsis seedlings displaying the trait in large-scale genetic screens showed that it can facilitate isolation of mutants with perturbations in auxin biosynthesis, transport and signaling. However, unlike transport/signaling mutants, the curled (or wavy) root phenotypes of auxin-deficient mutants were significantly induced by CKs and could be rescued by exogenous auxins. Mutants allelic to several known auxin biosynthesis mutants were re-isolated, but several new classes of auxin-deficient mutants were also isolated. The findings show that CK-induced root curling provides an effective marker for discovering genes involved in auxin biosynthesis or homeostasis.

  15. Preimplantation Genetic Diagnosis (PGD) for Monogenic Disorders: the Value of Concurrent Aneuploidy Screening.

    PubMed

    Goldman, Kara N; Nazem, Taraneh; Berkeley, Alan; Palter, Steven; Grifo, Jamie A

    2016-12-01

    Pre-implantation genetic diagnosis (PGD) has changed the landscape of clinical genetics by helping families reduce the transmission of monogenic disorders. However, given the high prevalence of embryonic aneuploidy, particularly in patients of advanced reproductive age, unaffected embryos remain at high risk of implantation failure or pregnancy loss due to aneuploidy. 24-chromosome aneuploidy screening has become widely utilized in routine in vitro fertilization (IVF) to pre-select embryos with greater pregnancy potential, but concurrent 24-chromosome aneuploidy screening has not become standard practice in embryos biopsied for PGD. We performed a retrospective cohort study of patients who underwent PGD with or without 24-chromosome aneuploidy screening to explore the value of concurrent screening. Among the PGD + aneuploidy-screened group (n = 355 blastocysts), only 25.6 % of embryos were both Single Gene Disorder (SGD)-negative (or carriers) and euploid; thus the majority of embryos were ineligible for transfer due to the high prevalence of aneuploidy. Despite a young mean age (32.4 ± 5.9y), 49.9 % of Blastocysts were aneuploid. The majority of patients (53.2 %) had ≥1 blastocyst that was Single Gene Disorder (SGD)-unaffected but aneuploid; without screening, these unaffected but aneuploid embryos would likely have been transferred resulting in implantation failure, pregnancy loss, or a pregnancy affected by chromosomal aneuploidy. Despite the transfer of nearly half the number of embryos in the aneuploidy-screened group (1.1 ± 0.3 vs. 1.9 ± 0.6, p < 0.0001), the implantation rate was higher (75 % vs. 53.3 %) and miscarriage rate lower (20 % vs. 40 %) (although not statistically significant). 24-chromosome aneuploidy screening when performed concurrently with PGD provides valuable information for embryo selection, and notably improves single embryo transfer rates.

  16. Screening, genetics, risk factors, and treatment of neonatal cataracts.

    PubMed

    Li, Jinyu; Xia, Chun-Hong; Wang, Eddie; Yao, Ke; Gong, Xiaohua

    2017-06-01

    Neonatal cataracts remain the most common cause of visual loss in children worldwide and have diverse, often unknown, etiologies. This review summarizes current knowledge about the detection, treatment, genetics, risk factors, and molecular mechanisms of congenital cataracts. We emphasize significant progress and topics requiring further study in both clinical cataract therapy and basic lens research. Advances in genetic screening and surgical technologies have improved the diagnosis, management, and visual outcomes of affected children. For example, mutations in lens crystallins and membrane/cytoskeletal components that commonly underlie genetically inherited cataracts are now known. However, many questions still remain regarding the causes, progression, and pathology of neonatal cataracts. Further investigations are also required to improve diagnostic criteria for determining the timing of appropriate interventions, such as the implantation of intraocular lenses and postoperative management strategies, to ensure safety and predictable visual outcomes for children. Birth Defects Research 109:734-743, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Impact of blastocyst biopsy and comprehensive chromosome screening technology on preimplantation genetic screening: a systematic review of randomized controlled trials.

    PubMed

    Dahdouh, Elias M; Balayla, Jacques; García-Velasco, Juan Antonio

    2015-03-01

    Embryonic aneuploidy is highly prevalent in IVF cycles and contributes to decreased implantation rates, IVF cycle failure and early pregnancy loss. Preimplantation genetic screening (PGS) selects the most competent (euploid) embryos for transfer, and has been proposed to improve IVF outcomes. Use of PGS with fluorescence-in-situ hybridization technology after day 3 embryo biopsy (PGS-v1) significantly lowers live birth rates and is not recommended for use. Comprehensive chromosome screening technology, which assesses the whole chromosome complement, can be achieved using different genetic platforms. Whether PGS using comprehensive chromosome screening after blastocyst biopsy (PGS-v2) improves IVF outcomes remains to be determined. A systematic review of randomized controlled trials was conducted on PGS-v2. Three trials met full inclusion criteria, comparing PGS-v2 and routine IVF care. PGS-v2 is associated with higher clinical implantation rates, and higher ongoing pregnancy rates when the same number of embryos is transferred in both PGS and control groups. Additionally, PGS-v2 improves embryo selection in eSET practice, maintaining the same ongoing pregnancy rates between PGS and control groups, while sharply decreasing multiple pregnancy rates. These results stem from good-prognosis patients undergoing IVF. Whether these findings can be extrapolated to poor-prognosis patients with decreased ovarian reserve remains to be determined. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  18. Genetic factors in toxicology: implications for toxicological screening

    SciTech Connect

    Festing, M.F.

    1987-01-01

    Methods of assessing the toxicity of xenobiotics have improved substantially during the last decade. However, as compounds become generally safer, the problem of individual variation in response assumes increasing relative importance. Environmental factors such as age, health and nutritional status, and interactions with other xenobiotics account for some of this variation, but genetic differences between individuals and races have important implications. In a few cases, Mendelian loci which control drug susceptibility (e.g., to isoniazid) have been described. However, in most cases the exact mode of inheritance has not yet been determined due to the problems of carrying out genetic studies in man. It is well established that many loci that are polymorphic in man are also so in laboratory animals, so much of this genetic variation should be picked up in preclinical screening, and could be used to more accurately predict potential variation in toxicity in man. Unfortunately, most toxicologists use only a single stock of laboratory animals, which does not show whether the response to a given xenobiotic is under genetic control. The design of animal tests would be improved by using more than one strain of genetically defined animals, and by paying more attention to genetic variation in responses to xenobiotics, both in animals and man. 97 references.

  19. Cost-effectiveness analysis of the genetic screening program for familial hypercholesterolemia in The Netherlands.

    PubMed

    Wonderling, David; Umans-Eckenhausen, Marina A W; Marks, Dalya; Defesche, Joep C; Kastelein, John J P; Thorogood, Margaret

    2004-02-01

    Familial hypercholesterolemia (FH) is associated with pronounced atherosclerosis leading to premature cardiovascular disease and untimely death. Despite the availability of effective preventative drug treatments, many affected individuals remain undiagnosed and untreated until they become symptomatic with cardiovascular disease. To assess the cost-effectiveness of systematic genetic screening of family members of persons diagnosed with FH, an analysis was conducted using data from a nationwide screening program for the identification of individuals with FH, instituted in The Netherlands in 1994, and from other sources. There was DNA testing of families with a known genetic defect to identify new cases of FH in the presymptomatic stage of the disease. After identification, most newly identified patients were started on cholesterol-lowering statin treatment. On average, new cases diagnosed by the screening program gained 3.3 years of life each. Twenty-six myocardial infarctions would be avoided for every 100 persons treated with statins between the ages of 18 and 60 years. The average total lifetime incremental costs, over all age ranges and both sexes, including costs for screening and testing, lifetime drug treatment, and treatment of cardiovascular events, was US dollars 7500 per new case identified. Cost per life-year gained was US dollars 8700. Therefore, systematic genetic screening of family members of persons diagnosed with FH is cost-effective in The Netherlands and should be considered for other settings.

  20. Genetic screening of Congenital Short Bowel Syndrome patients confirms CLMP as the major gene involved in the recessive form of this disorder.

    PubMed

    Alves, Maria M; Halim, Danny; Maroofian, Reza; de Graaf, Bianca M; Rooman, Raoul; van der Werf, Christine S; Van de Vijver, Els; Mehrjardi, Mohammad Yv; Aflatoonian, Majid; Chioza, Barry A; Baple, Emma L; Dehghani, Mohammadreza; Crosby, Andrew H; Hofstra, Robert Mw

    2016-11-01

    Congenital short bowel syndrome (CSBS) is an intestinal pediatric disorder, where patients are born with a dramatic shortened small intestine. Pathogenic variants in CLMP were recently identified to cause an autosomal recessive form of the disease. However, due to the rare nature of CSBS, only a small number of patients have been reported to date with variants in this gene. In this report, we describe novel inherited variants in CLMP in three CSBS patients derived from two unrelated families, confirming CLMP as the major gene involved in the development of the recessive form of CSBS.

  1. Screening for depression in hospitalized medical patients.

    PubMed

    IsHak, Waguih William; Collison, Katherine; Danovitch, Itai; Shek, Lili; Kharazi, Payam; Kim, Tae; Jaffer, Karim Y; Naghdechi, Lancer; Lopez, Enrique; Nuckols, Teryl

    2017-02-01

    Depression among hospitalized patients is often unrecognized, undiagnosed, and therefore untreated. Little is known about the feasibility of screening for depression during hospitalization, or whether depression is associated with poorer outcomes, longer hospital stays, and higher readmission rates. We searched PubMed and PsycINFO for published, peer-reviewed articles in English (1990-2016) using search terms designed to capture studies that tested the performance of depression screening tools in inpatient settings and studies that examined associations between depression detected during hospitalization and clinical or utilization outcomes. Two investigators reviewed each full-text article and extracted data. The prevalence of depression ranged from 5% to 60%, with a median of 33%, among hospitalized patients. Several screening tools identified showed high sensitivity and specificity, even when self-administered by patients or when abbreviated versions were administered by individuals without formal training. With regard to outcomes, studies from several individual hospitals found depression to be associated with poorer functional outcomes, worse physical health, and returns to the hospital after discharge. These findings suggest that depression screening may be feasible in the inpatient setting, and that more research is warranted to determine whether screening for and treating depression during hospitalization can improve patient outcomes. Journal of Hospital Medicine 2017;12:118-125. © 2017 Society of Hospital Medicine.

  2. Promising outcomes of screening for pancreatic cancer by genetic testing and endoscopic ultrasound.

    PubMed

    Sud, Anchal; Wham, Deborah; Catalano, Marc; Guda, Nalini M

    2014-04-01

    This study aimed to determine if screening patients based on certain cancer syndromes or family history criteria can lead to early detection of pancreatic cancer. This was a cohort study from 2008 to 2011 at a large tertiary referral center. A total of 30 patients met high-risk criteria after genetic counseling and were referred to a gastroenterologist for possible endoscopic ultrasound (EUS). Of the 30 patients, 16 underwent EUS. Subsequently, 3 patients had fine needle aspiration. Two patients had pancreatic adenocarcinoma, and 1 patient had an intraductal papillary mucinous neoplasm with low-grade dysplasia. The 2 patients with pancreatic adenocarcinoma both had breast cancer and BRCA2 mutations. The patient with the intraductal papillary mucinous neoplasm had Peutz-Jeghers syndrome. All 3 patients underwent surgery and have remained cancer free. Genetic risk assessment with EUS +/- fine needle aspiration in high-risk patients may lead to earlier detection of pancreatic cancer and potentially improve overall morbidity and mortality. Greater emphasis should be placed on screening patients for hereditary cancer syndromes that increase the risk of pancreatic cancer.

  3. Rapid genetic screening of Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies patients.

    PubMed

    Li, Xiaobo; Zi, Xiaohong; Li, Lin; Zhan, Yajing; Huang, Shunxiang; Li, Jin; Li, Xuning; Li, Xigui; Hu, Zhengmao; Xia, Kun; Tang, Beisha; Zhang, Ruxu

    2012-11-15

    We used the allele-specific PCR-double digestion method on peripheral myelin protein 22 (PMP22) to determine duplication and deletion mutations in the proband and family members of one family with Charcot-Marie-Tooth disease type 1 and one family with hereditary neuropathy with liability to pressure palsies. The proband and one subclinical family member from the Charcot-Marie-Tooth disease type 1 family had a PMP22 gene duplication; one patient from the hereditary neuropathy with liability to pressure palsies family had a PMP22 gene deletion. Electron microscopic analysis of ultrathin sections of the superficial peroneal nerve from the two probands demonstrated demyelination and myelin sheath hyperplasia, as well as an 'onion-like' structure in the Charcot-Marie-Tooth disease type 1A patient. We observed an irregular thickened myelin sheath and 'mouse-nibbled'-like changes in the patient with hereditary neuropathy with liability to pressure palsies. In the Charcot-Marie-Tooth disease type 1A patient, nerve electrophysiological examination revealed moderate-to-severe reductions in the motor and sensory conduction velocities of the bilateral median nerve, ulnar nerve, tibial nerve, and sural nerve. Moreover, the compound muscle action potential amplitude was decreased. In the patient with hereditary neuropathy with liability to pressure palsies, the nerve conduction velocity of the bilateral tibial nerve and sural nerve was moderately reduced, and the nerve conduction velocity of the median nerve and ulnar nerve of both upper extremities was slightly reduced.

  4. Phenotype databases for genetic screens in human cells.

    PubMed

    Rauscher, Benedikt; Valentini, Erica; Hardeland, Ulrike; Boutros, Michael

    2017-11-10

    Genetic screens are powerful tools to identify components that make up biological systems. Perturbations introduced by methods such as RNA interference (RNAi) or CRISPR/Cas9-mediated genome editing lead to biological phenotypes that can be examined to understand the molecular function of genes in the cell. Over the years, many of such experiments have been conducted providing a wealth of knowledge about genotype-to-phenotype relationships. These data are a rich source of information and it is in a common interest to make them available in a simplified and integrated format. Thus, an important challenge is that genetic screening data can be stored in databases in standardized ways, allowing users to gain new biological insights through data mining and integrated analyses. Here, we provide an overview of available phenotype databases for human cells. We review in detail two databases for high-throughput screens, GenomeRNAi and GenomeCRISPR, and describe how these resources are integrated into the German Network for Bioinformatics Infrastructure de.NBI as part of the European infrastructure for life-science information ELIXIR. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  5. Effects of genetic and environmental risk assessment feedback on colorectal cancer screening adherence.

    PubMed

    Myers, Ronald E; Ruth, Karen; Manne, Sharon L; Cocroft, James; Sifri, Randa; Ziring, Barry; Burgh, Desiree; Ross, Eric; Weinberg, David S

    2015-10-01

    Little is known about the impact of genetic and environmental risk assessment (GERA) feedback on colorectal cancer (CRC) screening. In a recently completed randomized trial, primary care patients received GERA feedback based on a blood test for genetic polymorphisms and serum folate level (GERA Group) versus usual care (Control Group). Subsequently, participants were offered CRC screening. Among participants who received GERA feedback, being at elevated risk was negatively associated with prospective CRC screening adherence. Secondary analyses of data from this study were performed to identify independent predictors of adherence among participants who received GERA feedback. We obtained baseline survey, follow-up survey, and endpoint medical records data on sociodemographic background, knowledge, psychosocial characteristics, risk status, and adherence for 285 GERA Group participants. Univariate and multivariable analyses were performed to identify predictors of CRC screening adherence. Following a 6-month outcomes observation period, we also conducted two focus groups with GERA Group participants to assess their perceptions of GERA risk feedback and screening. Content analyses of focus group data were evaluated to gain insights into participant response to risk feedback. Overall, half of GERA Group participants adhered to screening within 6 months after randomization. Multivariable analyses showed a statistically significant interaction between race and GERA feedback status relative to screening adherence (p = 0.043). Among participants who received average risk feedback, adherence was comparable among whites (49.7 %) and nonwhites (54.1 %); however, among those at elevated risk, adherence was substantially higher among whites (66.7 %) compared to nonwhites (33.3 %). Focus group findings suggest that whites were more likely than nonwhites to view elevated risk feedback as a prompt to screen. In response to receiving elevated risk feedback, nonwhites were

  6. Genetic Screening of Anderson-Fabry Disease in Probands Referred From Multispecialty Clinics.

    PubMed

    Favalli, Valentina; Disabella, Eliana; Molinaro, Mariadelfina; Tagliani, Marilena; Scarabotto, Anna; Serio, Alessandra; Grasso, Maurizia; Narula, Nupoor; Giorgianni, Carmela; Caspani, Clelia; Concardi, Monica; Agozzino, Manuela; Giordano, Calogero; Smirnova, Alexandra; Kodama, Takahide; Giuliani, Lorenzo; Antoniazzi, Elena; Borroni, Riccardo G; Vassallo, Camilla; Mangione, Filippo; Scelsi, Laura; Ghio, Stefano; Pellegrini, Carlo; Zedde, Marialuisa; Fancellu, Laura; Sechi, GianPietro; Ganau, Antonello; Piga, Stefania; Colucci, Annarita; Concolino, Daniela; Di Mascio, Maria Teresa; Toni, Danilo; Diomedi, Marina; Rapezzi, Claudio; Biagini, Elena; Marini, Massimiliano; Rasura, Maurizia; Melis, Maurizio; Nucera, Antonia; Guidetti, Donata; Mancuso, Michelangelo; Scoditti, Umberto; Cassini, Pamela; Narula, Jagat; Tavazzi, Luigi; Arbustini, Eloisa

    2016-09-06

    Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease, caused by defects of the alpha-galactosidase A (GLA) gene. AFD can affect the heart, brain, kidney, eye, skin, peripheral nerves, and gastrointestinal tract. Cardiology (hypertrophic cardiomyopathy), neurology (cryptogenic stroke), and nephrology (end-stage renal failure) screening studies suggest the prevalence of GLA variants is 0.62%, with diagnosis confirmation in 0.12%. This study sought to expand screening from these settings to include ophthalmology, dermatology, gastroenterology, internal medicine, pediatrics, and medical genetics to increase diagnostic yield and comprehensively evaluate organ involvement in AFD patients. In a 10-year prospective multidisciplinary, multicenter study, we expanded clinical, genetic, and biochemical screening to consecutive patients enrolled from all aforementioned clinical settings. We tested the GLA gene and α-galactosidase A activity in plasma and leukocytes. Inclusion criteria comprised phenotypical traits and absence of male-to-male transmission. Screening was extended to relatives of probands harboring GLA mutations. Of 2,034 probands fulfilling inclusion criteria, 37 (1.8%) were carriers of GLA mutations. Cascade family screening identified 60 affected relatives; clinical data were available for 4 affected obligate carriers. Activity of α-galactosidase A in plasma and leukocytes was diagnostic in male subjects, but not in female subjects. Of the 101 family members harboring mutations, 86 were affected, 10 were young healthy carriers, and 5 refused clinical evaluation. In the 86 patients, involved organs or organ systems included the heart (69%), peripheral nerves (46%), kidney (45%), eye (37%), brain (34%), skin (32%), gastrointestinal tract (31%), and auditory system (19%). Globotriaosylceramide accumulated in organ-specific and non-organ-specific cells in atypical and classic variants, respectively. Screening probands with clinically

  7. Common cancers--genetics, origin, prevention, screening: Parts I and II.

    PubMed

    Schifeling, D J; Horton, J; Tafelski, T J

    1997-10-01

    Carcinogenesis is a stepwise process that occurs through mutations of cancer-related genes. Five or more genes must be mutated before malignant transformation occurs in most adult cancers; in some childhood cancers as few as two mutated genes may be sufficient. A rare inherited mutation of a critical gene may predestine cancer to occur in one or more sites. This germline mutation is present in virtually every cell in the body, except half of the germ cells, which do not contain the mutated gene in their haploid chromosome set. These and other genes have been used to piece together a puzzle of regulatory systems that govern cell division and proliferation, as well as apoptosis or programmed cell death. Mutations of these genes result not only in increased cell proliferation but also in diminished cell death. Most genetic changes that occur during carcinogenesis are not inherited or germline. They are acquired after birth and are called somatic mutations. A somatic mutation affects only the mutated cell and its progeny. Each time a cell divides, there is a chance of somatic mutation, and therefore there always is a low, background risk for cancer and other malignant lesions. A far more prevalent cause of cancer-related death in the United States is environmental exposure. Such exposure causes somatic mutations of cancer-related genes through direct damage to DNA or through alteration of proliferation or cell death, which enhances the baseline risk for mutation. As carcinogenesis becomes understood, interventions may be designed that selectively interfere in important steps. Screening for cancer is based on the premise that one can treat a patient for a cancer that has not spread from its primary site. Nevertheless, cancer screening is controversial and often confusing. Issues of costs, risks versus benefits, physical time and effort, and patient compliance all affect the clinician's view of screening, often to the extent that the true value of this approach to cancer

  8. Recent advances in preimplantation genetic diagnosis and screening.

    PubMed

    Lu, Lina; Lv, Bo; Huang, Kevin; Xue, Zhigang; Zhu, Xianmin; Fan, Guoping

    2016-09-01

    Preimplantation genetic diagnosis/screening (PGD/PGS) aims to help couples lower the risks of transmitting genetic defects to their offspring, implantation failure, and/or miscarriage during in vitro fertilization (IVF) cycles. However, it is still being debated with regard to the practicality and diagnostic accuracy of PGD/PGS due to the concern of invasive biopsy and the potential mosaicism of embryos. Recently, several non-invasive and high-throughput assays have been developed to help overcome the challenges encountered in the conventional invasive biopsy and low-throughput analysis in PGD/PGS. In this mini-review, we will summarize the recent progresses of these new methods for PGD/PGS and discuss their potential applications in IVF clinics.

  9. [Genetic variants associated to male infertility in Mexican patients].

    PubMed

    Piña-Aguilar, Raúl Eduardo; Chima-Galán, María del Carmen; Yerena-de-vega, María de la Concepción A; Regalado-Hernández, Miguel Angel; Sánchez-Guerrero, Cecilia; García-Ortiz, Liliana; Santillán-Hernández, Yuritzi; Moreno-García, Jesús Daniel

    2013-05-01

    Recently Mexican Federation of Obstetrics and Gynecology Colleges (Federación Mexicana de Colegios de Obstetricia y Ginecologia, FEMECOG) published the Mexican guideline forthe management of male infertility, which suggests performing genetic laboratory tests as part of diagnosis and management of infertile patients and states that these should receive genetic counseling. This paper reviews the genetic approach proposed by Mexican guideline. A systematic review of medical literature was performed in Pubmed and Web of Knowledge from 1980 to 2012 in order to find reports of genetic variants associated to male infertility in Mexican patients. Also it is discussed the current knowledge of these variants, their clinical implications and finally the guidelines and recommendations for their molecular diagnosis. Most genetic variants in Mexican infertile patients are chromosome abnormalities. In relation to other variants there is only a report of Y chromosome microdeletions, repeated CAG in androgen receptor and more common mutations in CFTR, and other article reporting mutations in CFTR in patients with congenital absence of vas deferens. Little is known about the genetics of Mexican infertile patients apart from chromosome abnormalities. However, the contribution of genetics as etiology of male infertility is taking more relevance and currently the consensual management of infertile male should include the screening of genetic background. This review pretends to be a quick guide for clinicians who want to know about reports of genetic variants related to male infertility in Mexican population and how to approach their diagnosis.

  10. Swedish parents’ interest in preconception genetic carrier screening

    PubMed Central

    Ekstrand Ragnar, Maria; Kihlbom, Ulrik; Larsson, Margareta

    2016-01-01

    Introduction Genetic technologies advance rapidly. It is possible to undergo genetic carrier screening before pregnancy to examine genetic risks to future offspring. We aimed to investigate parents’ interest and motives towards preconception genetic carrier screening (PCS) as well as factors associated with interest in PCS. Material and methods Our study sample consists of 777 parent couples within the longitudinal Swedish Pregnancy Planning study. Women responded to questionnaires at three occasions: in early pregnancy, late pregnancy, and one year after childbirth. Male partners responded to one questionnaire one year after childbirth. Results One-third of the parents were positive (30% versus 34% of women and men, respectively), less than a third were negative (26% versus 28%), and 45% versus 38% were uncertain about whether to consider PCS before a future pregnancy. No differences in PCS interest were found between women and men (P = 0.091), but a higher proportion of women were concerned about negative consequences (53% versus 46%, P < 0.003) and were ‘opposed to such a way of child selection’ (31.8% versus 25.2%, P = 0.002). Factors associated with PCS interest were experiences of prenatal diagnostics and positive attitudes towards finding out or choosing sex of one’s child (women), and prenatal diagnostics, self-rated poor health, and pregnancy planning (men). Conclusion Both women and men had relatively high uncertainty towards PCS, but women were more concerned about negative consequences. The future extent of the clinical utility of PCS is currently unknown, but parents’ interests and doubts are important aspects to consider. PMID:27647125

  11. Assessing risk assessment: genetic testing and screening for complex disease.

    PubMed

    Cox, S M

    2006-11-01

    This paper reports on the presentations from the second session of a 2-day workshop on genetic diversity and science communication, organized by the Institute of Genetics. The four talks in this session (by Sarah Cunningham-Burley, Gail Geller, Michael Hayden, and Theresa Marteau) focused on the topic of risk assessment in the context of genetic testing, screening and preventive medicine for complex disease. Each talk underscored the urgency and importance of evaluating when and for whom risk assessment may be useful. A recurrent theme was the need to attend closely to the diverse ways that risk is constructed, perceived and communicated in a variety of contexts and the significant implications of this for laypersons as well as experts. Although there was no consensus on when genetic risk assessment ceases (or might begin) to be useful, ensuing dialogue between presenters and participants reflected what is perhaps a new and critical engagement with how risk assessment itself is assessed. In response to this impetus, I use the word RISK as a heuristic to identify, extract and amplify four tendencies that appear to advance understandings of risk assessment towards a more explicitly reflexive, interpretive, and situated form of knowing.

  12. Patients' Expectations of Screening and Preventive Treatments

    PubMed Central

    Hudson, Ben; Zarifeh, Abby; Young, Lorraine; Wells, J. Elisabeth

    2012-01-01

    PURPOSE An informed decision to accept a health care intervention requires an understanding of its likely benefit. This study assessed participants' estimates of the benefit, as well as minimum acceptable benefit, of screening for breast and bowel cancer and medication to prevent hip fracture and cardiovascular disease. METHODS Three general practitioners sent questionnaires to all registered patients aged 50 to 70 years. Patients agreeing to participate in the study were asked to estimate the number of events (fractures or deaths) prevented in a group of 5,000 patients undergoing each intervention over a period of 10 years, and to indicate the minimum number of events avoided by the intervention that they considered justified its use. The proportions of participants that overestimated each intervention's benefit were calculated, and univariate and multivariable analyses of predictors of response were performed. RESULTS The participation rate was 36%: 977 patients were invited to participate in the study, and 354 returned a completed questionnaire. Participants overestimated the degree of benefit conferred by all interventions: 90% of participants overestimated the effect of breast cancer screening, 94% overestimated the effect of bowel cancer screening, 82% overestimated the effect of hip fracture preventive medication, and 69% overestimated the effect of preventive medication for cardiovascular disease. Estimates of minimum acceptable benefit were more conservative, but other than for cardiovascular disease mortality prevention, most respondents indicated a minimum benefit greater than these interventions achieve. A lower level of education was associated with higher estimates of minimum acceptable benefit for all interventions. CONCLUSION Patients overestimated the risk reduction achieved with 4 examples of screening and preventive medications. A lower level of education was associated with higher minimum benefit to justify intervention use. This tendency to

  13. Genome-wide genetic screening with chemically mutagenized haploid embryonic stem cells.

    PubMed

    Forment, Josep V; Herzog, Mareike; Coates, Julia; Konopka, Tomasz; Gapp, Bianca V; Nijman, Sebastian M; Adams, David J; Keane, Thomas M; Jackson, Stephen P

    2017-01-01

    In model organisms, classical genetic screening via random mutagenesis provides key insights into the molecular bases of genetic interactions, helping to define synthetic lethality, synthetic viability and drug-resistance mechanisms. The limited genetic tractability of diploid mammalian cells, however, precludes this approach. Here, we demonstrate the feasibility of classical genetic screening in mammalian systems by using haploid cells, chemical mutagenesis and next-generation sequencing, providing a new tool to explore mammalian genetic interactions.

  14. Genetics in myeloma: genetic technologies and their application to screening approaches in myeloma.

    PubMed

    Talley, Polly J; Chantry, Andrew D; Buckle, Clive H

    2015-03-01

    Despite advances in the treatment of multiple myeloma (MM), it remains an incurable malignant disease. Myeloma genetics is intrinsically complex, but it offers an opportunity to categorize the disease and apply a personalized medicine approach. Research into the genetics of myeloma is moving at a fast pace and is highlighting areas and patient cohorts likely to benefit from specific treatment. Targeting residual disease is likely to be crucial to improved clinical outcome. Patients in clinical trials are more likely to receive genetic diagnosis than non-trial patients, for whom access is ad hoc and dependent upon regional commissioning arrangements. Relating genetics to potential treatment pathways will become crucial for improved myeloma outcomes. Universal access to standardized genetic testing will facilitate modern personalized treatments. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Good laboratory practices for biochemical genetic testing and newborn screening for inherited metabolic disorders.

    PubMed

    2012-04-06

    screening laboratories. The recommended practices address the benefits of using a quality management system approach, factors to consider before introducing new tests, establishment and verification of test performance specifications, the total laboratory testing process (which consists of the preanalytic, analytic, and postanalytic phases), confidentiality of patient information and test results, and personnel qualifications and responsibilities for laboratory testing for inherited metabolic diseases. These recommendations are intended for laboratories that perform biochemical genetic testing to improve the quality of laboratory services and for newborn screening laboratories to ensure the quality of laboratory practices for inherited metabolic disorders. These recommendations also are intended as a resource for medical and public health professionals who evaluate laboratory practices, for users of laboratory services to facilitate their collaboration with newborn screening systems and use of biochemical genetic tests, and for standard-setting organizations and professional societies in developing future laboratory quality standards and practice recommendations. This report complements Good Laboratory Practices for Molecular Genetic Testing for Heritable Diseases and Conditions (CDC. Good laboratory practices for molecular genetic testing for heritable diseases and conditions. MMWR 2009;58 [No. RR-6]) to provide guidance for ensuring and improving the quality of genetic laboratory services and public health outcomes. Future recommendations for additional areas of genetic testing will be considered on the basis of continued monitoring and evaluation of laboratory practices, technology advancements, and the development of laboratory standards and guidelines.

  16. Emergency preparedness for genetics centers, laboratories, and patients: the Southeast Region Genetics Collaborative strategic plan.

    PubMed

    Andersson, Hans C; Perry, William; Bowdish, Bruce; Floyd-Browning, Phaidra

    2011-10-01

    Emergencies occur unpredictably and interrupt routine genetic care. The events after hurricanes Katrina and Rita have led to the recognition that a coherent plan is necessary to ensure continuity of operations for genetic centers and laboratories, including newborn screening. No geographic region is protected from the effects of a variety of potential emergencies. Regional and national efforts have begun to address the need for such preparedness, but a plan for ensuring continuity of operations by creating an emergency preparedness plan must be developed for each genetic center and laboratory, with attention to the interests of patients. This article describes the first steps in development of an emergency preparedness plan for individual centers.

  17. Referring patients for a medical genetics consultation and genetic counseling.

    PubMed

    Sutton, Reid

    2011-01-01

    Clinical geneticists and genetic counselors provide diagnosis and counseling for genetic disorders affecting every organ system and every age group. Genetic counselors are more focused on informing patients and families about the inheritance of a genetic disorder and providing recurrence risk counseling, support and information about a diagnosis and reproductive options. Medical geneticists may also share some of these roles in addition to establishing a diagnosis and providing medical management. Medical Geneticists receive training in ACGME-accredited residency programs and are certified by the American Board of Medical Genetics. Genetic counseling is a masters degree program and certification is granted by the American Board of Genetic Counseling. When a patient/family is referred to a Clinical Geneticist, they may expect a thorough evaluation in an effort to establish a diagnosis that may provide information about etiology, prognosis, therapy and recurrence risk. Copyright © 2011 S. Karger AG, Basel.

  18. Progress with genetic cardiomyopathies: screening, counseling, and testing in dilated, hypertrophic, and arrhythmogenic right ventricular dysplasia/cardiomyopathy.

    PubMed

    Hershberger, Ray E; Cowan, Jason; Morales, Ana; Siegfried, Jill D

    2009-05-01

    This review focuses on the genetic cardiomyopathies: principally dilated cardiomyopathy, with salient features of hypertrophic cardiomyopathy and arrhythmogenic right ventricular dysplasia/cardiomyopathy, regarding genetic etiology, genetic testing, and genetic counseling. Enormous progress has recently been made in identifying genetic causes for each cardiomyopathy, and key phenotype and genotype information is reviewed. Clinical genetic testing is rapidly emerging with a principal rationale of identifying at-risk asymptomatic or disease-free relatives. Knowledge of a disease-causing mutation can guide clinical surveillance for disease onset, thereby enhancing preventive and treatment interventions. Genetic counseling is also indicated for patients and their family members regarding the symptoms of their cardiomyopathy, its inheritance pattern, family screening recommendations, and genetic testing options and possible results.

  19. Screening of the CFTR gene in Indian patients.

    PubMed

    Deepak, Rani R; Ashavaid, Tester F

    2012-12-01

    Cystic fibrosis (CF) has been observed to be far more common in India, than was previously thought. Variability in CF clinical symptoms among individuals, results in diagnostic errors. Also, CF diagnostic facilities are not available at all diagnostic centers across India. Sweat test (gold standard for CF diagnosis) has some limitations. Mutation analysis, therefore, would be useful in detecting the mutant CF alleles in Indian patients. This study, aimed at identifying common CF transmembrane conductance regulator (CFTR) mutations, to develop a molecular diagnostic test in Indian patients, and establish genotype-phenotype correlation. Mutation identification was performed by single stranded conformation polymorphism (SSCP) screening, followed by DNA sequencing of regions with an abnormal SSCP pattern. ∆F508 accounts for about 53% of CF alleles. A substantial proportion of these patients have rare and/or novel mutations. Eight novel and 12 known polymorphisms were also identified. Considering the high percentage of rare/novel mutations, along with ethnic history of Indian population, we can speculate that the remaining uncharacterized mutations might also not be prevalent mutations. The total number of CF disease-causing mutations in Indian patients is very large. Thus, DNA-based population screening will be complicated, and an indirect genetic diagnosis (screening entire gene) would be necessary to characterize all mutations.

  20. An update of preimplantation genetic diagnosis in gene diseases, chromosomal translocation, and aneuploidy screening

    PubMed Central

    Chang, Li-Jung; Chen, Shee-Uan; Tsai, Yi-Yi; Hung, Chia-Cheng; Fang, Mei-Ya

    2011-01-01

    Preimplantation genetic diagnosis (PGD) is gradually widely used in prevention of gene diseases and chromosomal abnormalities. Much improvement has been achieved in biopsy technique and molecular diagnosis. Blastocyst biopsy can increase diagnostic accuracy and reduce allele dropout. It is cost-effective and currently plays an important role. Whole genome amplification permits subsequent individual detection of multiple gene loci and screening all 23 pairs of chromosomes. For PGD of chromosomal translocation, fluorescence in-situ hybridization (FISH) is traditionally used, but with technical difficulty. Array comparative genomic hybridization (CGH) can detect translocation and 23 pairs of chromosomes that may replace FISH. Single nucleotide polymorphisms array with haplotyping can further distinguish between normal chromosomes and balanced translocation. PGD may shorten time to conceive and reduce miscarriage for patients with chromosomal translocation. PGD has a potential value for mitochondrial diseases. Preimplantation genetic haplotyping has been applied for unknown mutation sites of single gene disease. Preimplantation genetic screening (PGS) using limited FISH probes in the cleavage-stage embryo did not increase live birth rates for patients with advanced maternal age, unexplained recurrent abortions, and repeated implantation failure. Polar body and blastocyst biopsy may circumvent the problem of mosaicism. PGS using blastocyst biopsy and array CGH is encouraging and merit further studies. Cryopreservation of biopsied blastocysts instead of fresh transfer permits sufficient time for transportation and genetic analysis. Cryopreservation of embryos may avoid ovarian hyperstimulation syndrome and possible suboptimal endometrium. PMID:22384431

  1. Technical report: Ethical and policy issues in genetic testing and screening of children.

    PubMed

    Ross, Lainie Friedman; Ross, Laine Friedman; Saal, Howard M; David, Karen L; Anderson, Rebecca R

    2013-03-01

    The genetic testing and genetic screening of children are commonplace. Decisions about whether to offer genetic testing and screening should be driven by the best interest of the child. The growing literature on the psychosocial and clinical effects of such testing and screening can help inform best practices. This technical report provides ethical justification and empirical data in support of the proposed policy recommendations regarding such practices in a myriad of settings.

  2. Prostate Cancer Screening

    MedlinePlus

    ... Genetics of Prostate Cancer Prostate Cancer Screening Research Prostate Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Prostate Cancer Key Points Prostate cancer is a disease in ...

  3. Key elements for designing and performing a CRISPR/Cas9-based genetic screen.

    PubMed

    Shang, Wanjing; Wang, Fei; Fan, Gaofeng; Wang, Haopeng

    2017-09-22

    Reverse genetic screens are invaluable for uncovering gene functions, but are traditionally hampered by some technical limitations. Over the past few years, since the advent of the revolutionary CRISPR/Cas9 technology, its power in genome editing has been harnessed to overcome the traditional limitations in reverse genetic screens, with successes in various biological contexts. Here, we outline these CRISPR/Cas9-based screens, provide guidance on the design of effective screens and discuss the potential future directions of development of this field. Copyright © 2017 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

  4. Applying theological developments to bioethical issues such as genetic screening.

    PubMed

    Mallia, Pierre; ten Have, Henk

    2005-01-01

    Catholic movements within the centre of Roman Catholic doctrine recently have discussed Trinitarian theology as applied to sciences, arts, economics, health and other social areas. We explore the possibilities Trinitarian theology offers to bioethical debate, concentrating particularly on genetic screening and testing. It is important therefore to analyse the philosophical implications of this approach onto the bioethical world, where much disagreement occurs on fundamental issues. It is Catholic basic teaching to recognize and see God's hand in plurality, not merely as a cliche and then doing what we feel is right, but to recognize how to live in a pluralistic world. We recognize, in agreement with these theologians, that in order for a Trinitarian mode of understanding to be used by those doing bioethical debate, there is a need to depart from fundamentalism.

  5. Screening for Depression Patients in Family Medicine

    PubMed Central

    Alic, Alma; Pranjic, Nurka; Selmanovic, Senada; Alibasic, Esad; Alic, Fahrudin; Ramic, Enisa; Spahic-Sarajlic, Selvedina

    2014-01-01

    ABSTRACT Goal: The aims are to establish the prevalence of newfound, unidentified cases of depressive disorder by screening with the Becks Depression scale; To establish a comparative relationship with self-identified cases of depression in the patients in the family medicine; To assess the significance of the BDI in screening practice of family medicine. Patients and methods: A prospective study was conducted anonymously by Beck's Depression scale (Beck Depression Questionnaire org.-BDI) and specially created short questionnaire. The study included 250 randomly selected patients (20-60 years), users of services in family medicine in “Dom Zdravlja” Zenica, and the final number of respondents with included in the study was 126 (51 male, 75 female; response or response rate 50.4%). Exclusion factor was previously diagnosed and treated mental disorder. Participation was voluntary and respondents acknowledge the validity of completing the questionnaire. BDI consists of 21 items. Answers to questions about symptoms were ranked according to the Likert type scale responses from 0-4 (from irrelevant to very much). Respondents expressed themselves on personal perception of depression, whether are or not depressed. Results: Depression was observed in 48% of patients compared to 31% in self estimate depression analyzed the questionnaires. The negative trend in the misrecognition of depression is -17% (48:31). Depression was significantly more frequent in unemployed compared to employed respondents (p=0.001). The leading symptom in both sexes is the perception of lost hope (59% of cases). Conclusion: All respondents in family medicine care in Zenica showed a high percentage of newly detected (17%) patients with previously unrecognized depression. BDI is a really simple and effective screening tool for the detection and identification of persons with symptoms of depression. PMID:24783910

  6. Comprehensive preimplantation genetic screening and sperm deoxyribonucleic acid fragmentation from three males carrying balanced chromosome rearrangements.

    PubMed

    Ramos, Laia; Daina, Gemma; Del Rey, Javier; Ribas-Maynou, Jordi; Fernández-Encinas, Alba; Martinez-Passarell, Olga; Boada, Montserrat; Benet, Jordi; Navarro, Joaquima

    2015-09-01

    To assess whether preimplantation genetic screening can successfully identify cytogenetically normal embryos in couples carrying balanced chromosome rearrangements in addition to increased sperm DNA fragmentation. Comprehensive preimplantation genetic screening was performed on three couples carrying chromosome rearrangements. Sperm DNA fragmentation was assessed for each patient. Academic center. One couple with the male partner carrying a chromosome 2 pericentric inversion and two couples with the male partners carrying a Robertsonian translocation (13:14 and 14:21, respectively). A single blastomere from each of the 18 cleavage-stage embryos obtained was analysed by metaphase comparative genomic hybridization. Single- and double-strand sperm DNA fragmentation was determined by the alkaline and neutral Comet assays. Single- and double-strand sperm DNA fragmentation values and incidence of chromosome imbalances in the blastomeres were analyzed. The obtained values of single-strand sperm DNA fragmentation were between 47% and 59%, and the double-strand sperm DNA fragmentation values were between 43% and 54%. No euploid embryos were observed in the couple showing the highest single-strand sperm DNA fragmentation. However, euploid embryos were observed in the other two couples: embryo transfer was performed, and pregnancy was achieved by the couple showing the lowest sperm DNA fragmentation values. Preimplantation genetic screening enables the detection of euploid embryos in couples affected by balanced chromosome rearrangements and increased sperm DNA fragmentation. Even though sperm DNA fragmentation may potentially have clinical consequences on fertility, comprehensive preimplantation genetic screening allows for the identification and transfer of euploid embryos. Copyright © 2015. Published by Elsevier Inc.

  7. Detection of genetic alterations in hereditary colorectal cancer screening.

    PubMed

    Pineda, Marta; González, Sara; Lázaro, Conxi; Blanco, Ignacio; Capellá, Gabriel

    2010-11-10

    There are two major hereditary colorectal cancer syndromes: Adenomatous Polyposis, secondary to APC germline alterations (FAP, Familial Adenomatous Polyposis) or secondary to MUTYH germline alterations (MAP, MUTYH associated Polyposis), and Lynch syndrome, associated with germline mutations in mismatch repair genes (MLH1, MSH2, MSH6 and PMS2). The elucidation of their genetic basis has depicted an increasingly complex picture that has lead to the implementation of complex diagnostic algorithms that include both tumor profiling and germline analyses. A variety of techniques at the DNA, RNA and protein level are used to screen for molecular alterations both in tumor biopsies (microsatellite instability analysis, mismatch repair protein immunohistochemistry, BRAF-Val600Glu detection and MLH1 promoter hypermethylation analysis) and in the germline (point mutation screening, copy number assessment). Also functional tests are more often used to characterize variants of unknown significance. Methodological issues associated with the techniques analyzed, as well as the algorithms used, are discussed. 2009 Elsevier B.V. All rights reserved.

  8. [Genetic screening to determine an etiologic diagnosis in children with mental retardation].

    PubMed

    Alliende, M Angélica; Cámpora, Laura; Curotto, Bianca; Toro, Jessica; Valiente, Alf; Castillo, Marcela; Cortés, Fanny; Trigo, César; Alvarado, Cecilia; Silva, Manuel; Caru, Margarita

    2008-12-01

    Mental retardation or intellectual disability affects 2% of the general population, but in 60% to 70% of cases the real cause of this retardation is not known. An early etiologic diagnosis of intellectual disability can lead to opportunities for improved educational interventions, reinforcing weak areas and providing a genetic counseling to the family. To search genetic diseases underlying intellectual disabilities of children attending a special education school. A clinical geneticist performed the history and physical examination in one hundred and three students aged between 5 and 24 years (51 males). A blood sample was obtained in 92 of them for a genetic screening that included a standard karyotype, fragile X molecular genetic testing and search for inborn errors of metabolism by tandem mass spectrometry. This approach yielded an etiological diagnosis in as much as 29 patients. Three percent of them had a fragile X syndrome. Inborn errors of metabolism were not detected. This type of screening should be done always in children with intellectual disability to establish an etiological diagnosis.

  9. Patients’ Ratings of Genetic Conditions Validate a Taxonomy to Simplify Decisions about Preconception Carrier Screening via Genome Sequencing

    PubMed Central

    Leo, Michael C.; McMullen, Carmit; Wilfond, Benjamin S.; Lynch, Frances; Reiss, Jacob A.; Gilmore, Marian J.; Himes, Patricia; Kauffman, Tia L.; Davis, James V.; Jarvik, Gail P.; Berg, Jonathan; Harding, Cary; Kennedy, Kathleen; Kostiner-Simpson, Dana; Quigley, Denise; Richards, C. Sue; Rope, Alan F.; Goddard, Katrina A.B.

    2016-01-01

    Advances in genome sequencing and gene discovery have created opportunities to efficiently assess more genetic conditions than ever before. Given the large number of conditions that can be screened, the implementation of expanded carrier screening using genome sequencing will require practical methods of simplifying decisions about the conditions for which patients want to be screened. One method to simplify decision making is to generate a taxonomy based on expert judgment. However, expert perceptions of condition attributes used to classify these conditions may differ from those used by patients. To understand whether expert and patient perceptions differ, we asked women who had received preconception genetic carrier screening in the last 3 years to fill out a survey to rate the attributes (predictability, controllability, visibility, and severity) of several autosomal recessive or X-linked genetic conditions. These conditions were classified into one of five taxonomy categories developed by subject experts (significantly shortened lifespan, serious medical problems, mild medical problems, unpredictable medical outcomes, and adult-onset conditions). A total of 193 women provided 739 usable ratings across 20 conditions. The mean ratings and correlations demonstrated that participants made distinctions across both attributes and categories. Aggregated mean attribute ratings across categories demonstrated logical consistency between the key features of each attribute and category, although participants perceived little difference between the mild and serious categories. This study provides empirical evidence for the validity of our proposed taxonomy, which will simplify patient decisions for results they would like to receive from preconception carrier screening via genome sequencing. PMID:26792268

  10. Genetic Counseling and Screening of Consanguineous Couples and Their Offspring: Recommendations of the National Society of Genetic Counselors.

    PubMed

    Bennett, Robin L; Motulsky, Arno G; Bittles, Alan; Hudgins, Louanne; Uhrich, Stefanie; Doyle, Debra Lochner; Silvey, Kerry; Scott, C Ronald; Cheng, Edith; McGillivray, Barbara; Steiner, Robert D; Olson, Debra

    2002-04-01

    The objective of this document is to provide recommendations for genetic counseling and screening for consanguineous couples (related as second cousins or closer) and their offspring with the goals of1. providing preconception reproductive options2. improving pregnancy outcome and identifying reproductive choices3. reducing morbidity and mortality in the 1st years of life, and4. respecting psychosocial and multicultural issues.The recommendations are the opinions of a multicenter working group (the Consanguinity Working Group (CWG)) with expertise in genetic counseling, medical genetics, biochemical genetics, genetic epidemiology, pediatrics, perinatology, and public health genetics, which was convened by the National Society of Genetic Counselors (NSGC). The consensus of the CWG and NSGC reviewers is that beyond a thorough medical family history with follow-up of significant findings, no additional preconception screening is recommended for consanguineous couples. Consanguineous couples should be offered similar genetic screening as suggested for any couple of their ethnic group. During pregnancy, consanguineous couples should be offered maternal-fetal serum marker screening and high-resolution fetal ultrasonography. Newborns should be screened for impaired hearing and detection of treatable inborn errors of metabolism. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a health care provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations.

  11. Vitrified/warmed single blastocyst transfer in preimplantation genetic diagnosis/preimplantation genetic screening cycles.

    PubMed

    Huang, Jin; Li, Rong; Lian, Ying; Chen, Lixue; Shi, Xiaodan; Qiao, Jie; Liu, Ping

    2015-01-01

    To investigate the single blastocyst transfer in preimplantation genetic diagnosis (PGD)/preimplantation genetic screening (PGS) cycles. 80 PGD/PGS cycles undergoing blastocyst biopsy were studied. There were 88 warming cycles during the study period. Only one warmed blastocyst was transferred per cycle. The outcomes were followed up to the infants were born. The embryo implantation rate was 54.55% (48/88). The clinical pregnancy rate was 54.55% (48/88) per transfer cycle and 60% (48/80) per initial PGD/PGS cycle. There was no multi-pregnant in this study. The live birth rate was 42.05% (37/88) per transfer cycle and 46.25% (37/80) per initial PGD/PGS cycle. In PGD/PGS cycles, single blastocyst transfer reduces the multiple pregnancy rate without affecting the clinical outcomes.

  12. Incorporating Health Literacy Screening Into Patients' Health Assessment.

    PubMed

    Sand-Jecklin, Kari; Daniels, Christine S; Lucke-Wold, Noelle

    2017-04-01

    Low health literacy (HL) has been associated with several negative health outcomes, yet routine HL screening is not commonplace. This study's purpose was to determine the feasibility of incorporating HL screening into the electronic health record (EHR) of patients admitted to a large Mid-Atlantic teaching hospital. After Registered Nurse (RN) training, the HL screening was implemented for all adult patients upon admission. After implementation, RNs were surveyed about the feasibility of HL screening, and patient EHRs were reviewed for HL status. Results indicated that RNs were receptive to HL screening. Approximately 20% of all patients screened were at risk for low HL, with HL scores decreasing as age increased. Patients with low HL had significantly higher hospital readmissions, even when controlling for age and number of health conditions. Further research is needed to determine how healthcare providers alter their patient interactions if they have knowledge that patients are at risk for having low HL.

  13. The Regional Genetic and Newborn Screening Service Collaboratives: The First Two Years

    ERIC Educational Resources Information Center

    Puryear, Michele; Weissman, Gloria; Watson, Michael; Mann, Marie; Strickland, Bonnie; van Dyck, Peter C.

    2006-01-01

    Newborn screening and genetic technologies are expanding and changing rapidly, increasing the demand for genetic specialty services. Because of the scarcity and geographic maldistribution of genetic specialty services, access to these services is a critical issue. This article discusses some of the efforts initiated by the Maternal and Child…

  14. Genetic counseling following the detection of hemoglobinopathy trait on the newborn screen is well received, improves knowledge, and relieves anxiety.

    PubMed

    Kladny, Beth; Williams, Andrea; Gupta, Ashish; Gettig, Elizabeth A; Krishnamurti, Lakshmanan

    2011-07-01

    The primary purpose of newborn screening for hemoglobinopathies is the presymptomatic diagnosis and early treatment of sickle cell disease. Hemoglobinopathy traits detected on the newborn screening provide an opportunity for genetic counseling of families regarding the trait and information that may impact reproductive decisions of the parents. We describe the results of a study to determine the impact of newborn screening and genetic counseling on the lives of families in which an abnormal hemoglobin trait had been identified. From June 2003 to December 2009, families of children with trait attending a clinic visit and receiving professional genetic counseling were asked to participate in a semistructured follow-up survey regarding their experience and the impact of genetic counseling on their families. Of the 300 patients seen in clinic during the specified time period, 209 consented to be recontacted and 114 have completed the survey. Eighty-five percent of responders reported knowing that the newborn screen had been performed, but only 55% understood the purpose of newborn screening. When asked about the effect of finding out that trait was present in their baby, 19% reported feeling guilty or upset, whereas 4% believed that their partner blamed them for the child's results. That genetic counseling was found to be beneficial was indicated by the fact that 99% reported that their questions were answered, 82% reported feeling less anxious, and 78% discussed the trait with their partner after the appointment. Genetic counseling after newborn screening relieves anxiety, provides knowledge, facilitates dialog within families and between partners about hemoglobinopathy trait, and was seen as a positive experience for the majority of responders.

  15. Measuring informed choice in population-based reproductive genetic screening: a systematic review

    PubMed Central

    Ames, Alice Grace; Metcalfe, Sylvia Ann; Archibald, Alison Dalton; Duncan, Rony Emily; Emery, Jon

    2015-01-01

    Genetic screening and health-care guidelines recommend that programmes should facilitate informed choice. It is therefore important that accurate measures of informed choice are available to evaluate such programmes. This review synthesises and appraises measures used to evaluate informed choice in population-based genetic screening programmes for reproductive risk. Databases were searched for studies offering genetic screening for the purpose of establishing reproductive risk to an adult population sample, in which aspects of informed choice were measured. Studies were included if, at a minimum, measures of uptake of screening and knowledge were used. Searches identified 1462 citations and 76 studies were reviewed in full text; 34 studies met the inclusion criteria. Over 20 different measures of informed choice were used. Many measures lacked adequate validity and reliability data. This systematic review will inform future evaluation of informed choice in population genetic screening programmes. PMID:24848746

  16. Parkinson’s Disease in Saudi Patients: A Genetic Study

    PubMed Central

    Al-Mubarak, Bashayer R.; Bohlega, Saeed A.; Alkhairallah, Thamer S.; Magrashi, Amna I.; AlTurki, Maha I.; Khalil, Dania S.; AlAbdulaziz, Basma S.; Abou Al-Shaar, Hussam; Mustafa, Abeer E.; Alyemni, Eman A.; Alsaffar, Bashayer A.; Tahir, Asma I.; Al Tassan, Nada A.

    2015-01-01

    Parkinson’s disease (PD) is one of the major causes of parkinsonism syndrome. Its characteristic motor symptoms are attributable to dopaminergic neurons loss in the midbrain. Genetic advances have highlighted underlying molecular mechanisms and provided clues to potential therapies. However, most of the studies focusing on the genetic component of PD have been performed on American, European and Asian populations, whereas Arab populations (excluding North African Arabs), particularly Saudis remain to be explored. Here we investigated the genetic causes of PD in Saudis by recruiting 98 PD-cases (sporadic and familial) and screening them for potential pathogenic mutations in PD-established genes; SNCA, PARKIN, PINK1, PARK7/DJ1, LRRK2 and other PD-associated genes using direct sequencing. To our surprise, the screening revealed only three pathogenic point mutations; two in PINK1 and one in PARKIN. In addition to mutational analysis, CNV and cDNA analysis was performed on a subset of patients. Exon/intron dosage alterations in PARKIN were detected and confirmed in 2 cases. Our study suggests that mutations in the ORF of the screened genes are not a common cause of PD in Saudi population; however, these findings by no means exclude the possibility that other genetic events such as gene expression/dosage alteration may be more common nor does it eliminate the possibility of the involvement of novel genes. PMID:26274610

  17. Employment discrimination implications of genetic screening in the workplace under Title VII and the Rehabilitation Act.

    PubMed

    Canter, E F

    1984-01-01

    The emergence of genetic screening techniques will permit employers to exclude hypersusceptible individuals from potentially hazardous workplace environments. The denial of employment opportunities to these individuals, however, may constitute discrimination. This Note analyzes genetic screening cases with respect to currently available remedies contained in Title VII of the Civil Rights Act of 1964 and the Rehabilitation Act of 1973. The Note concludes that Title VII claims may succeed but only in limited circumstances and that Rehabilitation Act claims will encounter numerous obstacles to relief. Additionally, the Note discusses some of the implications of the use of genetic screening in the workplace.

  18. Changing trends in carrier screening for genetic disease in the United States.

    PubMed

    Nazareth, Shivani B; Lazarin, Gabriel A; Goldberg, James D

    2015-10-01

    Genetic disease is the leading cause of infant death in the United States, accounting for approximately 20% of annual infant mortality. Advances in genomic medicine and technological platforms have made possible low cost, pan-ethnic expanded genetic screening that enables obstetric care providers to offer screening for over 100 recessive genetic diseases. However, the rapid integration of genomic medicine into routine obstetric practice has raised some concerns about the practical implementation of such testing. These changing trends in carrier screening, along with concerns and potential solutions, will be addressed.

  19. Genetic highthroughput screening in retinitis pigmentosa based on high resolution melting (HRM) analysis.

    PubMed

    Anasagasti, Ander; Barandika, Olatz; Irigoyen, Cristina; Benitez, Bruno A; Cooper, Breanna; Cruchaga, Carlos; López de Munain, Adolfo; Ruiz-Ederra, Javier

    2013-10-24

    Retinitis Pigmentosa (RP) involves a group of genetically determined retinal diseases caused by a large number of mutations that result in rod photoreceptor cell death followed by gradual death of cone cells. Most cases of RP are monogenic, with more than 80 associated genes identified so far. The high number of genes and variants involved in RP, among other factors, is making the molecular characterization of RP a real challenge for many patients. Although HRM has been used for the analysis of isolated variants or single RP genes, as far as we are concerned, this is the first study that uses HRM analysis for a high-throughput screening of several RP genes. Our main goal was to test the suitability of HRM analysis as a genetic screening technique in RP, and to compare its performance with two of the most widely used NGS platforms, Illumina and PGM-Ion Torrent technologies. RP patients (n=96) were clinically diagnosed at the Ophthalmology Department of Donostia University Hospital, Spain. We analyzed a total of 16 RP genes that meet the following inclusion criteria: 1) size: genes with transcripts of less than 4 kb; 2) number of exons: genes with up to 22 exons; and 3) prevalence: genes reported to account for, at least, 0.4 % of total RP cases worldwide. For comparison purposes, RHO gene was also sequenced with Illumina (GAII; Illumina), Ion semiconductor technologies (PGM; Life Technologies) and Sanger sequencing (ABI 3130xl platform; Applied Biosystems). Detected variants were confirmed in all cases by Sanger sequencing and tested for co-segregation in the family of affected probands. We identified a total of 65 genetic variants, 15 of which (23%) were novel, in 49 out of 96 patients. Among them, 14 (4 novel) are probable disease-causing genetic variants in 7 RP genes, affecting 15 patients. Our HRM analysis-based study, proved to be a cost-effective and rapid method that provides an accurate identification of genetic RP variants. This approach is effective for

  20. Risks of Prostate Cancer Screening

    MedlinePlus

    ... Genetics of Prostate Cancer Prostate Cancer Screening Research Prostate Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Prostate Cancer Key Points Prostate cancer is a disease in ...

  1. Familial Mediterranean fever without cardinal symptoms and role of genetic screening.

    PubMed

    Ulas, T; Buyukhatipoglu, H; Bes, C; Dal, M S; Hacıbekiroglu, I; Apucu, H G; Borlu, F

    2012-07-19

    Familial Mediterranean fever is an autosomal recessive disorder characterized by paroxysmal episodes of fever and serosal inflammation. The classical presentation is fever and severe recurrent abdominal pain due to serositis that lasts for one to three days and the resolves spontaneously. Between the episodes patients are asymptomatic. Ninety-five percent of patients with familial mediterranean fever have painful episodes localized to the abdomen, which is usually the dominant manifestation of the disease. Herein, we present a case of 34-year-old man with incomplete abdominal pain episode of familial mediterranean fever limited to the epigastrum and had no cardinals symptoms of this disease. The diagnosis was made by genetic screening. Successful treatment response was achieved by colchicine.

  2. Stakeholder perspectives on the implementation of genetic carrier screening in a changing landscape.

    PubMed

    Holtkamp, Kim C A; Vos, Evelien M; Rigter, Tessel; Lakeman, Phillis; Henneman, Lidewij; Cornel, Martina C

    2017-02-16

    In most countries, genetic carrier screening is neither offered, nor embedded in mainstream healthcare. Technological developments have triggered a two-fold transition in carrier screening: the expansion from screening one single disorder to many disorders simultaneously, and offering screening universally, regardless of ancestry. This study aims to identify general and population-specific barriers and needs reflected by stakeholders regarding the implementation of carrier screening in a changing landscape. Seventeen semi-structured interviews were conducted with Dutch key stakeholders working in the practical and scientific field of carrier screening. The constellation approach was used to categorise barriers and needs into three levels: culture, structure and practice. Barriers on a cultural level include: undecidedness about the desirability of carrier screening, and a lack of priority of screening in mainstream healthcare. On a structural level barriers included: need for organisational structures in healthcare for embedding carrier screening, need for guidelines, financial structures, practical tools for overcoming challenges during counselling, and a need for training and education of both professionals and the public. A lack of demand for screening by the public, and a need for a division of responsibilities were barriers on a practical level. The absence of a collective sense of urgency for genetic carrier screening, a lack of organisational structures, and uncertainty or even disagreement about the responsibilities seem to be important barriers in the implementation of carrier screening. Stakeholders therefore suggest that change agents should be formally acknowledged to strategically plan broadening of current initiatives and attune different stakeholders.

  3. Genetic screening for chromosomal abnormalities and Y chromosome microdeletions in Chinese infertile men.

    PubMed

    Fu, Li; Xiong, Da-Ke; Ding, Xian-Ping; Li, Chuang; Zhang, Li-Yuan; Ding, Min; Nie, Shuang-Shuang; Quan, Qiang

    2012-06-01

    To investigate the frequency and type of both chromosomal abnormalities and Y chromosome microdeletions and analyze their association with defective spermatogenesis in Chinese infertile men. This is a single center study. Karyotyping using G-banding and screening for Y chromosome microdeletion by multiplex polymerase chain reaction(PCR)were performed in 200 controls and 1,333 infertile men, including 945 patients with non-obstructive azoospermia and 388 patients with severe oligozoospermia. Out of 1,333 infertile patients, 154(11.55%) presented chromosomal abnormalities. Of these, 139 of 945 (14.71%) were from the azoospermic and 15 of 388 (3.87%) from the severe oligozoospermic patient groups. The incidence of sex chromosomal abnormalities in men with azoospermia was 11.53% compared with 1.03% in men with severe oligozoospermia (P < 0.01). Also 144 of 1,333(10.80%) patients presented Y chromosome microdeletions. The incidence of azoospermia factor(AZF) microdeletion was 11.75% and 8.51% in patients with azoospermia and severe oligozoospermia respectively. Deletion of AZFc was the most common and deletions in AZFa or AZFab or AZFabc were found in azoospermic men. In addition, 34 patients had chromosomal abnormalities among the 144 patients with Y chromosome microdeletions. No chromosomal abnormality and microdeletion in AZF region were detected in controls. There was a high incidence (19.80%) of chromosomal abnormalities and Y chromosomal microdeletions in Chinese infertile males with azoospermia or severe oligozoospermia. These findings strongly suggest that genetic screening should be advised to infertile men before starting assisted reproductive treatments.

  4. Multiplicity of experimental approaches to therapy for genetic muscle diseases and necessity for population screening.

    PubMed

    Laing, Nigel G

    2008-01-01

    Currently a multiplicity of experimental approaches to therapy for genetic muscle diseases is being investigated. These include replacement of the missing gene, manipulation of the gene message, repair of the mutation, upregulation of an alternative gene and pharmacological interventions targeting a number of systems. A number of these approaches are in current clinical trials. There is considerable anticipation that perhaps more than one of the approaches will finally prove of clinical benefit, but there are many voices of caution. No matter which approaches might ultimately prove effective, there is a consensus that for most benefit to the patients it will be necessary to start treatment as early as possible. A consensus is also developing that the only way to do this is to implement population-based newborn screening to identify affected children shortly after birth. Population-based newborn screening is currently practised in very few places in the world and it brings with it implications for prevention rather than cure of genetic muscle diseases.

  5. Screening for spinal stenosis in achondroplastic patients undergoing limb lengthening.

    PubMed

    Fernandes, James A; Devalia, Kailash L; Moras, Prem; Pagdin, Jonathan; Jones, Stanley; Mcmullan, John

    2014-03-01

    The need for a screening programme for spinal stenosis in children with achondroplasia undergoing limb lengthening was identified in a tertiary limb reconstruction service. The aim of this study was to evaluate whether screening would identify the 'at risk' group. A total of 26 achondroplastic patients underwent our screening programme. Canal diameters were measured by MRI. Neurosurgical interventions were recorded. Of the patients, 13 had severe foramen magnum narrowing. Six patients required single or multiple surgical decompressions. We identified female sex, delayed milestones and a tight cervicomedullary junction as high risks. We stress upon the importance of developing a nationalized screening programme with guidelines to identify a high-risk group.

  6. Alternative to the soft-agar assay that permits high-throughput drug and genetic screens for cellular transformation

    PubMed Central

    Rotem, Asaf; Janzer, Andreas; Izar, Benjamin; Ji, Zhe; Doench, John G.; Garraway, Levi A.; Struhl, Kevin

    2015-01-01

    Colony formation in soft agar is the gold-standard assay for cellular transformation in vitro, but it is unsuited for high-throughput screening. Here, we describe an assay for cellular transformation that involves growth in low attachment (GILA) conditions and is strongly correlated with the soft-agar assay. Using GILA, we describe high-throughput screens for drugs and genes that selectively inhibit or increase transformation, but not proliferation. Such molecules are unlikely to be found through conventional drug screening, and they include kinase inhibitors and drugs for noncancer diseases. In addition to known oncogenes, the genetic screen identifies genes that contribute to cellular transformation. Lastly, we demonstrate the ability of Food and Drug Administration-approved noncancer drugs to selectively kill ovarian cancer cells derived from patients with chemotherapy-resistant disease, suggesting this approach may provide useful information for personalized cancer treatment. PMID:25902495

  7. Patient Navigation in a Colorectal Cancer Screening Program

    PubMed Central

    Escoffery, Cam; Fernandez, Maria E.; Vernon, Sally W.; Liang, Shuting; Maxwell, Annette E.; Allen, Jennifer D.; Dwyer, Andrea; Hannon, Peggy A.; Kohn, Marlana; DeGroff, Amy

    2015-01-01

    Context Colorectal cancer (CRC) is the second leading cause of cancer death among cancers affecting both men and women in the United States. The Centers for Disease Control and Prevention’s Colorectal Cancer Control Program (CRCCP) supports both direct clinical screening services (screening provision) and activities to promote screening at the population level (screening promotion). Objective The purpose of this study was to characterize patient navigation (PN) programs for screening provision and promotion for the first 1 to 2 years of program funding. Participants We conducted a cross-sectional survey of the 29 CRCCP grantees (25 states and 4 tribal organizations) and 14 in-depth interviews to assess program implementation. Main Outcome Measures The survey and interview guide collected information on CRC screening provision and promotion activities and PN, including the structure of the PN program, characteristics of the navigators, funding mechanism, and navigators’ activities. Results Twenty-four of 28 CRCCP grantees of the survey used PN for screening provision whereas 18 grantees used navigation for screening promotion. Navigators were often trained in nursing or public health. Navigation activities were similar for both screening provision and promotion, and common tasks included assessing and responding to patient barriers to screening, providing patient education, and scheduling appointments. For screening provision, activities centered on making reminder calls, educating patients on bowel preparation for colonoscopies, and tracking patients for completion of the tests. Navigation may influence screening quality by improving patients’ bowel preparation for colonoscopies. Conclusions Our study provides insights into PN across a federally funded CRC program. Results suggest that PN activities may be instrumental in recruiting people into cancer screening and ensuring completed screening and follow-up. PMID:25140407

  8. Focal congenital hyperinsulinism managed by medical treatment: a diagnostic algorithm based on molecular genetic screening.

    PubMed

    Maiorana, Arianna; Barbetti, Fabrizio; Boiani, Arianna; Rufini, Vittoria; Pizzoferro, Milena; Francalanci, Paola; Faletra, Flavio; Nichols, Colin G; Grimaldi, Chiara; de Ville de Goyet, Jean; Rahier, Jacques; Henquin, Jean-Claude; Dionisi-Vici, Carlo

    2014-11-01

    Congenital hyperinsulinism (CHI) requires rapid diagnosis and treatment to avoid irreversible neurological sequelae due to hypoglycaemia. Aetiological diagnosis is instrumental in directing the appropriate therapy. Current diagnostic algorithms provide a complete set of diagnostic tools including (i) biochemical assays, (ii) genetic facility and (iii) state-of-the-art imaging. They consider the response to a therapeutic diazoxide trial an early, crucial step before proceeding (or not) to specific genetic testing and eventually imaging, aimed at distinguishing diffuse vs focal CHI. However, interpretation of the diazoxide test is not trivial and can vary between research groups, which may lead to inappropriate decisions. Objective of this report is proposing a new algorithm in which early genetic screening, rather than diazoxide trial, dictates subsequent clinical decisions. Two CHI patients weaned from parenteral glucose infusion and glucagon after starting diazoxide. No hypoglycaemia was registered during a 72-h continuous glucose monitoring (CGMS), or hypoglycaemic episodes were present for no longer than 3% of 72-h. Normoglycaemia was obtained by low-medium dose diazoxide combined with frequent carbohydrate feeds for several years. We identified monoallelic, paternally inherited mutations in KATP channel genes, and (18) F-DOPA PET-CT revealed a focal lesion that was surgically resected, resulting in complete remission of hypoglycaemia. Although rare, some patients with focal lesions may be responsive to diazoxide. As a consequence, we propose an algorithm that is not based on a 'formal' diazoxide response but on genetic testing, in which patients carrying paternally inherited ABCC8 or KCNJ11 mutations should always be subjected to (18) F-DOPA PET-CT. © 2014 John Wiley & Sons Ltd.

  9. Hepatitis C virus screening in patients with cancer receiving chemotherapy.

    PubMed

    Hwang, Jessica P; Suarez-Almazor, Maria E; Torres, Harrys A; Palla, Shana L; Huang, Donna S; Fisch, Michael J; Lok, Anna S F

    2014-05-01

    Reactivation of hepatitis C virus (HCV) replication can occur in patients receiving immunosuppressive therapy. We aimed to determine the prevalence and predictors of HCV screening at the onset of chemotherapy among patients with cancer. We conducted a retrospective cohort study of adults with cancer who were newly registered at MD Anderson Cancer Center from January 2004 to April 2011 and received chemotherapy. The primary study outcome was HCV antibody (anti-HCV) screening at chemotherapy onset. We calculated screening prevalence and predictors by comparing characteristics of screened and unscreened patients using multivariable logistic regression. A total of 141,877 new patients with cancer were registered at MD Anderson during the study period, of whom 16,773 (11.8%) received chemotherapy and met inclusion criteria. A total of 2,330 patients (13.9%) were screened for HCV, and 35 (1.5%) tested positive. Only 42% of patients with exposure-type HCV risk factors, such as HIV infection, injection drug use, hemodialysis, or hemophilia, were screened. Birth after 1965, Asian race, HCV risk factors, and anticipated rituximab therapy were significant predictors of HCV screening; black patients and patients with solid tumors were significantly less likely to be screened. The only significant predictor of a positive anti-HCV result was birth during 1945 to 1965. HCV screening rates were low, even among patients with risk factors, and the groups with the highest rates of screening did not match the groups with the highest rates of a positive test result. Misconceptions may exist about which patients should be screened for HCV infection. Copyright © 2014 by American Society of Clinical Oncology.

  10. A genetic history questionnaire-based system in primary prenatal care to screen for selected fetal disorders.

    PubMed

    Bradley, Linda A; Kloza, Edward M; Haddow, Paula K; Beauregard, Laurent J; Johnson, Judith L; Haddow, James E

    2007-01-01

    DNA (and other) diagnostic tests are now available for a number of serious, but uncommon, fetal disorders. We designed and evaluated a screening system for this purpose in primary care, coupled with targeted information for practitioners and patients. We developed a 15-question family history form for completion by office staff or patients, addressing conditions for which definitive diagnosis was available, linked to secondary questionnaires to follow up on "yes" answers. Guidelines for assessing risk, follow-up recommendations, and information resources were also linked. Following pilot testing, this screening system was introduced throughout Maine. We enrolled 212 providers (85-90% of the state's pregnancies). In a subsequent survey, 85% of the practices were screening all new patients and 3% some; 12% did not use the system. Time for form completion averaged 7 min. Overall, provider satisfaction was 4.4 on a five-point scale. Patients responded favorably; a minority was anxious or overwhelmed. Total referral calls to Maine's genetic/perinatal centers did not increase, but calls about family history of genetic disorders or maternal conditions increased significantly. This screening system for guiding appropriate use of DNA (and other) testing in pregnancy can be used successfully in primary care.

  11. 'Inside-out', back-to-front: a model for clinical population genetic screening.

    PubMed Central

    Shickle, D; Harvey, I

    1993-01-01

    Developments in DNA technology have resulted in a dramatic increase in the number of genes identified. With the localisation of a gene it is possible to devise procedures suitable for mass carrier screening programmes. Until recently mass carrier screening was only possible for a limited number of disorders, for example, Tay-Sachs disease and haemoglobinopathies. Counselling possible carriers was based on estimations of risk. The momentum towards mass carrier screening is likely to be increased by gene therapy. Carrier screening for cystic fibrosis alone will have dramatic implications for genetic service provision as 4 to 5% of the UK population carry the CF gene. The potential for genetic screening of multifactorial diseases, for example, cancers, should also be considered. The existing organisation of genetic services is likely to be inadequate. A new specialty of clinical population genetics is required. A model is proposed of clinical population genetic screening programmes, organised under a 'common umbrella' led by a public health physician, while screening and follow up will remain the responsibility of the appropriate clinician. PMID:8411031

  12. 'Inside-out', back-to-front: a model for clinical population genetic screening.

    PubMed

    Shickle, D; Harvey, I

    1993-07-01

    Developments in DNA technology have resulted in a dramatic increase in the number of genes identified. With the localisation of a gene it is possible to devise procedures suitable for mass carrier screening programmes. Until recently mass carrier screening was only possible for a limited number of disorders, for example, Tay-Sachs disease and haemoglobinopathies. Counselling possible carriers was based on estimations of risk. The momentum towards mass carrier screening is likely to be increased by gene therapy. Carrier screening for cystic fibrosis alone will have dramatic implications for genetic service provision as 4 to 5% of the UK population carry the CF gene. The potential for genetic screening of multifactorial diseases, for example, cancers, should also be considered. The existing organisation of genetic services is likely to be inadequate. A new specialty of clinical population genetics is required. A model is proposed of clinical population genetic screening programmes, organised under a 'common umbrella' led by a public health physician, while screening and follow up will remain the responsibility of the appropriate clinician.

  13. Referring patients for telephone counseling to promote colorectal cancer screening.

    PubMed

    Luckmann, Roger; Costanza, Mary E; Rosal, Milagros; White, Mary Jo; Cranos, Caroline

    2013-09-01

    To determine the feasibility, acceptability, and outcomes of a telephone counseling intervention promoting colorectal cancer (CRC) screening when patients are referred for counseling by primary care providers (PCPs). Interventional cohort study with no formal control group. PCPs in 3 practices were prompted to address CRC screening in patient encounters and, if appropriate, to recommend referral for telephone counseling. A telephone counselor called referred patients, made an appointment for a counseling call, and mailed an educational booklet to patients. Counseling included education about CRC and screening tests, motivational interviewing, barrier counseling, and facilitated referral for colonoscopy or mailing of a fecal occult blood testing kit. About 7 months following counseling, electronic records were searched for evidence of colonoscopy. PCPs addressed CRC screening with 1945 patients, most of whom were up-to-date with CRC testing, recommended counseling referral to 362, and of these 180 (49.7%) accepted the referral. A total of 140 (77.8%) of referred patients were contacted and 67 (37.2%) received counseling. After counseling 93.9% were planning on CRC screening compared with 54.6% at the beginning of the call. Of those planning a colonoscopy, 53.2% received one within 7 months. Referring patients for telephone counseling to promote CRC screening may be feasible and acceptable to PCPs and to some patients, and may increase CRC screening. Further evaluation of the intervention may be warranted to compare the rate of screening associated with the intervention to rates related to usual care and to other interventions.

  14. Predictive features of breast cancer on Mexican screening mammography patients

    NASA Astrophysics Data System (ADS)

    Rodriguez-Rojas, Juan; Garza-Montemayor, Margarita; Trevino-Alvarado, Victor; Tamez-Pena, José Gerardo

    2013-02-01

    Breast cancer is the most common type of cancer worldwide. In response, breast cancer screening programs are becoming common around the world and public programs now serve millions of women worldwide. These programs are expensive, requiring many specialized radiologists to examine all images. Nevertheless, there is a lack of trained radiologists in many countries as in Mexico, which is a barrier towards decreasing breast cancer mortality, pointing at the need of a triaging system that prioritizes high risk cases for prompt interpretation. Therefore we explored in an image database of Mexican patients whether high risk cases can be distinguished using image features. We collected a set of 200 digital screening mammography cases from a hospital in Mexico, and assigned low or high risk labels according to its BIRADS score. Breast tissue segmentation was performed using an automatic procedure. Image features were obtained considering only the segmented region on each view and comparing the bilateral di erences of the obtained features. Predictive combinations of features were chosen using a genetic algorithms based feature selection procedure. The best model found was able to classify low-risk and high-risk cases with an area under the ROC curve of 0.88 on a 150-fold cross-validation test. The features selected were associated to the differences of signal distribution and tissue shape on bilateral views. The model found can be used to automatically identify high risk cases and trigger the necessary measures to provide prompt treatment.

  15. Healthcare and patient costs of a proactive chlamydia screening programme: the Chlamydia Screening Studies project

    PubMed Central

    Robinson, Suzanne; Roberts, Tracy; Barton, Pelham; Bryan, Stirling; Macleod, John; McCarthy, Anne; Egger, Matthias; Sanford, Emma; Low, Nicola

    2007-01-01

    Background and objective Most economic evaluations of chlamydia screening do not include costs incurred by patients. The objective of this study was to estimate both the health service and private costs of patients who participated in proactive chlamydia screening, using mailed home‐collected specimens as part of the Chlamydia Screening Studies project. Methods Data were collected on the administrative costs of the screening study, laboratory time and motion studies and patient‐cost questionnaire surveys were conducted. The cost for each screening invitation and for each accepted offer was estimated. One‐way sensitivity analysis was conducted to explore the effects of variations in patient costs and the number of patients accepting the screening offer. Results The time and costs of processing urine specimens and vulvo‐vaginal swabs from women using two nucleic acid amplification tests were similar. The total cost per screening invitation was £20.37 (95% CI £18.94 to 24.83). This included the National Health Service cost per individual screening invitation £13.55 (95% CI £13.15 to 14.33) and average patient costs of £6.82 (95% CI £5.48 to 10.22). Administrative costs accounted for 50% of the overall cost. Conclusions The cost of proactive chlamydia screening is comparable to those of opportunistic screening. Results from this study, which is the first to collect private patient costs associated with a chlamydia screening programme, could be used to inform future policy recommendations and provide unique primary cost data for economic evaluations. PMID:17229792

  16. A model for patient-direct screening and referral for familial cancer risk

    PubMed Central

    Geller, Melissa A.; Vogel, Rachel Isaksson; Church, Timothy R.; Leininger, Anna; Bakke, Angela; Madoff, Robert D.

    2016-01-01

    Patients at increased familial risk of cancer are sub-optimally identified and referred for genetic counseling. We describe a systematic model for information collection, screening and referral for hereditary cancer risk. Individuals from three different clinical and research populations were screened for hereditary cancer risk using a two-tier process: a 7-item screener followed by review of family history by a genetic counselor and application of published criteria. A total of 869 subjects participated in the study; 769 in this high risk population had increased familial cancer risk based on the screening questionnaire. Of these eligible participants, 500 (65.0 %) provided family histories and 332 (66.4 %) of these were found to be at high risk of a hereditary cancer syndrome, 102 (20.4 %) at moderate familial cancer risk, and 66 (13.2 %) at average risk. Three months following receipt of the risk result letter, nearly all respondents found the process at least somewhat helpful (98.4 %). All participants identified as high-risk were mailed a letter recommending genetic counseling and were provided appointment tools. After 1 year, only 13 (7.3 %) of 179 high risk respondents reported pursuit of recommended genetic counseling. Participants were willing to provide family history information for the purposes of risk assessment; however, few patients pursued recommended genetic services. This suggests that cancer family history registries are feasible and viable but that further research is needed to increase the uptake of genetic counseling. PMID:27350384

  17. A model for patient-direct screening and referral for familial cancer risk.

    PubMed

    Niendorf, Kristin B; Geller, Melissa A; Vogel, Rachel Isaksson; Church, Timothy R; Leininger, Anna; Bakke, Angela; Madoff, Robert D

    2016-10-01

    Patients at increased familial risk of cancer are sub-optimally identified and referred for genetic counseling. We describe a systematic model for information collection, screening and referral for hereditary cancer risk. Individuals from three different clinical and research populations were screened for hereditary cancer risk using a two-tier process: a 7-item screener followed by review of family history by a genetic counselor and application of published criteria. A total of 869 subjects participated in the study; 769 in this high risk population had increased familial cancer risk based on the screening questionnaire. Of these eligible participants, 500 (65.0 %) provided family histories and 332 (66.4 %) of these were found to be at high risk of a hereditary cancer syndrome, 102 (20.4 %) at moderate familial cancer risk, and 66 (13.2 %) at average risk. Three months following receipt of the risk result letter, nearly all respondents found the process at least somewhat helpful (98.4 %). All participants identified as high-risk were mailed a letter recommending genetic counseling and were provided appointment tools. After 1 year, only 13 (7.3 %) of 179 high risk respondents reported pursuit of recommended genetic counseling. Participants were willing to provide family history information for the purposes of risk assessment; however, few patients pursued recommended genetic services. This suggests that cancer family history registries are feasible and viable but that further research is needed to increase the uptake of genetic counseling.

  18. Newborn Screening for Genetic-Metabolic Diseases: Progress, Principles and Recommendations.

    ERIC Educational Resources Information Center

    Holtzman, Neil A.

    This monograph, designed for persons involved in the organization and regulation of screening of newborns infants for Phenylketonuria (PKU) and other genetic-metabolic diseases reviews new developments in the field, makes recommendations, and provides information about specific conditions other than PKU that are detectable by screening. Discussed…

  19. Results of a nationwide screening for Anderson-Fabry disease among dialysis patients.

    PubMed

    Kotanko, Peter; Kramar, Reinhard; Devrnja, Danijela; Paschke, Eduard; Voigtländer, Till; Auinger, Martin; Pagliardini, Severo; Spada, Marco; Demmelbauer, Klaus; Lorenz, Matthias; Hauser, Anna-Christine; Kofler, Hans-Jörg; Lhotta, Karl; Neyer, Ulrich; Pronai, Wolfgang; Wallner, Manfred; Wieser, Clemens; Wiesholzer, Martin; Zodl, Herbert; Födinger, Manuela; Sunder-Plassmann, Gere

    2004-05-01

    Anderson-Fabry disease is possibly underdiagnosed in patients with end-stage renal disease. Nationwide screening was therefore undertaken for Anderson-Fabry disease among dialysis patients in Austria. Screening for alpha-galactosidase A (AGAL) deficiency was performed by a blood spot test. In patients with a positive screening test, AGAL activity in leukocytes was determined. Individuals with decreased leukocyte AGAL activity were subjected to mutation testing in the GLA gene. Fifty (90.9%) of 55 Austrian hemodialysis centers participated in this study; 2480 dialysis patients (80.1% of the Austrian dialysis population) were screened. In 85 patients, the screening test was positive (85 of 2480, 3.42%; women, 3.32%; men, 3.50%). Among these 85 patients, 4 men (in 3 of whom Anderson-Fabry disease was already known before screening) had a severely decreased and 11 subjects had a borderline low AGAL activity. Genetic testing revealed mutations associated with Fabry disease in all four men with severely decreased AGAL activity resulting in a prevalence of 0.161% for the entire study population. A nationwide screening of dialysis patients permitted detection of a hitherto unknown man with Anderson-Fabry disease. The overall prevalence among dialysis patients was at least ten times higher as compared with recent registry data. Screening programs among patients with end-stage renal disease, especially men, should be put in place to identify families with Anderson-Fabry disease who probably may benefit from specific clinical care, and perhaps from enzyme replacement therapy. In dialysis patients, however, there is no evidence to support enzyme replacement therapy at present.

  20. Genetic counseling for beta-thalassemia trait following health screening in a health maintenance organization: comparison of programmed and conventional counseling.

    PubMed

    Fisher, L; Rowley, P T; Lipkin, M

    1981-11-01

    Providing adequate counseling of patients identified in genetic screening programs is a major responsibility and expense. Adults in a health maintenance organization, unselected for interest, were screened for beta-thalassemia trait as part of preventive health care. Counseling was provided by either a trained physician (conventional counseling) or by a videotape containing the same information followed by an opportunity to question a trained physician (programmed counseling). Immediately before and after counseling, knowledge of thalassemia, knowledge of genetics, and mood change were assessed by questionnaire. Comparable mood changes and similar learning about thalassemia and genetics occurred with both counseling methods. Thus, as judged by immediate effects on knowledge and mood, videotaped instruction can greatly reduce professional time required for genetic counseling and facilitate the incorporation of genetic screening into primary health care.

  1. Evaluation of a novel electronic genetic screening and clinical decision support tool in prenatal clinical settings.

    PubMed

    Edelman, Emily A; Lin, Bruce K; Doksum, Teresa; Drohan, Brian; Edelson, Vaughn; Dolan, Siobhan M; Hughes, Kevin; O'Leary, James; Vasquez, Lisa; Copeland, Sara; Galvin, Shelley L; DeGroat, Nicole; Pardanani, Setul; Gregory Feero, W; Adams, Claire; Jones, Renee; Scott, Joan

    2014-07-01

    "The Pregnancy and Health Profile" (PHP) is a free prenatal genetic screening and clinical decision support (CDS) software tool for prenatal providers. PHP collects family health history (FHH) during intake and provides point-of-care risk assessment for providers and education for patients. This pilot study evaluated patient and provider responses to PHP and effects of using PHP in practice. PHP was implemented in four clinics. Surveys assessed provider confidence and knowledge and patient and provider satisfaction with PHP. Data on the implementation process were obtained through semi-structured interviews with administrators. Quantitative survey data were analyzed using Chi square test, Fisher's exact test, paired t tests, and multivariate logistic regression. Open-ended survey questions and interviews were analyzed using qualitative thematic analysis. Of the 83% (513/618) of patients that provided feedback, 97% felt PHP was easy to use and 98% easy to understand. Thirty percent (21/71) of participating physicians completed both pre- and post-implementation feedback surveys [13 obstetricians (OBs) and 8 family medicine physicians (FPs)]. Confidence in managing genetic risks significantly improved for OBs on 2/6 measures (p values ≤0.001) but not for FPs. Physician knowledge did not significantly change. Providers reported value in added patient engagement and reported mixed feedback about the CDS report. We identified key steps, resources, and staff support required to implement PHP in a clinical setting. To our knowledge, this study is the first to report on the integration of patient-completed, electronically captured and CDS-enabled FHH software into primary prenatal practice. PHP is acceptable to patients and providers. Key to successful implementation in the future will be customization options and interoperability with electronic health records.

  2. Fabry disease: experience of screening dialysis patients for Fabry disease.

    PubMed

    Kusano, Eiji; Saito, Osamu; Akimoto, Tetsu; Asano, Yasushi

    2014-04-01

    The prevalence rate for Fabry disease is conventionally considered to be 1 case in 40,000; however, due to increased screening accuracy, reports now suggest that prevalence is 1 case in 1,500 among male children, and it is likely that the clinical importance of the condition will increase in the future. In dialysis patients to date, prevalence rates are between 0.16 and 1.2 %. Globotriaosylsphingosine (Lyso-GL-3), which is a substrate of α-galactosidase A (α-Gal A), has surfaced as a new biomarker, and is also effective in the determination and monitoring of the effects of enzyme replacement therapy. In terms of genetic abnormalities, the E66Q mutation has recently become a topic of discussion, and although doubts have been expressed over whether or not it is the gene responsible for Fabry disease, there is still a strong possibility that it is a functional genetic polymorphism. At present, the standard treatment for Fabry disease is enzyme replacement therapy, and in order to overcome the problems involved with this, a method of producing recombinant human α-Gal A using methanol-assimilating yeast, and chemical or medicinal chaperone treatment are of current interest. Migalastat hydrochloride is known as a pharmacological chaperone, but is currently in Phase III global clinical trials. Adding saposin B to modified α-N-acetyl galactosaminidase is also under consideration as a treatment method.

  3. Genetic heterogeneity of megaloblastic anaemia type 1 in Tunisian patients.

    PubMed

    Bouchlaka, Chiraz; Maktouf, Chokri; Mahjoub, Bahri; Ayadi, Abdelkarim; Sfar, M Tahar; Sioud, Mahbouba; Gueddich, Neji; Belhadjali, Zouheir; Rebaï, Ahmed; Abdelhak, Sonia; Dellagi, Koussay

    2007-01-01

    Megaloblastic anaemia 1 (MGA1) is a rare autosomal recessive condition characterized by selective intestinal vitamin B12 malabsorption and proteinuria. More than 200 MGA1 patients have been identified worldwide, but the disease is relatively prevalent in Finland, Norway and several Eastern Mediterranean regions. MGA1 is genetically heterogeneous and can be caused by mutations in either the cubilin (CUBN) or the amnionless (AMN) gene. In the present study we investigated the molecular defect underlying MGA1 in nine Tunisian patients belonging to six unrelated consanguineous families. Haplotype and linkage analyses, using microsatellite markers surrounding both CUBN and AMN genes, indicated that four out of the six families were likely to be linked to the CUBN gene. Patients from these families were screened for the Finnish, Mediterranean and Arabian mutations already published. None of the screened mutations could be detected in our population. One family showed a linkage to AMN gene. Direct screening of the AMN gene allowed the identification of the c.208-2A>G mutation, previously described in a Jewish Israeli patient of Tunisian origin and in Turkish patients. This suggests that the c.208-2A>G mutation may derive from a single Mediterranean founder ancestor. For the last family, haplotype analysis excluded both CUBN and AMN genes, suggesting the existence of a third locus that may cause MGA1.

  4. Moderating Effects of Autism on Parent Views of Genetic Screening for Aggression

    ERIC Educational Resources Information Center

    May, Michael E.; Brandt, Rachel C.; Bohannan, Joseph K.

    2012-01-01

    Advances in gene-environment interaction research have revealed genes that are associated with aggression. However, little is known about parent perceptions of genetic screening for behavioral symptoms like aggression as opposed to diagnosing disabilities. These perceptions may influence future research endeavors involving genetic linkage studies…

  5. Moderating Effects of Autism on Parent Views of Genetic Screening for Aggression

    ERIC Educational Resources Information Center

    May, Michael E.; Brandt, Rachel C.; Bohannan, Joseph K.

    2012-01-01

    Advances in gene-environment interaction research have revealed genes that are associated with aggression. However, little is known about parent perceptions of genetic screening for behavioral symptoms like aggression as opposed to diagnosing disabilities. These perceptions may influence future research endeavors involving genetic linkage studies…

  6. Genetics patients' perspectives on clinical genomic testing

    PubMed Central

    McGowan, Michelle L; Glinka, Allison; Highland, Janelle; Asaad, George; Sharp, Richard R

    2014-01-01

    Aims Advances in next-generation sequencing technologies make it possible to envisage multiple contexts in which genomic tools might be used to enhance patient care. We describe how genetics patients and their caregivers view the promises and perils of clinical genomic testing. Patients & methods Fifty-one interviews with patients and parents of pediatric patients seeking genetic evaluation at an academic medical center. Results Themes from interviews include participants' enthusiasm for clinical genomic testing for diagnostic purposes, medical benefits and concerns about emotional and psychosocial burdens resulting from clinical genomic testing. Conclusion By clarifying these patients' and caregivers' views of clinical genomic testing, the findings we report can help to anticipate other patients' reactions to new forms of personalized medicine enabled by genomic technologies. PMID:24955098

  7. ESHRE Task Force on Ethics and Law 21: genetic screening of gamete donors: ethical issues.

    PubMed

    Dondorp, W; De Wert, G; Pennings, G; Shenfield, F; Devroey, P; Tarlatzis, B; Barri, P; Diedrich, K; Eichenlaub-Ritter, U; Tüttelmann, F; Provoost, V

    2014-07-01

    This Task Force document explores the ethical issues involved in the debate about the scope of genetic screening of gamete donors. Calls for expanded donor screening arise against the background of both occasional findings of serious but rare genetic conditions in donors or donor offspring that were not detected through present screening procedures and the advent of new genomic technologies promising affordable testing of donors for a wide range of conditions. Ethical principles require that all stakeholders' interests are taken into account, including those of candidate donors. The message of the profession should be that avoiding all risks is impossible and that testing should remain proportional.

  8. Is preimplantation genetic diagnosis the ideal embryo selection method in aneuploidy screening?

    PubMed

    Sahin, Levent; Bozkurt, Murat; Sahin, Hilal; Gürel, Aykut; Yumru, Ayse Ender

    2014-10-01

    To select cytogenetically normal embryos, preimplantation genetic diagnosis (PGD) aneuploidy screening (AS) is used in numerous centers around the world. Chromosomal abnormalities lead to developmental problems, implantation failure, and early abortion of embryos. The usefulness of PGD in identifying single-gene diseases, human leukocyte antigen typing, X-linked diseases, and specific genetic diseases is well-known. In this review, preimplantation embryo genetics, PGD research studies, and the European Society of Human Reproduction and Embryology PGD Consortium studies and reports are examined. In addition, criteria for embryo selection, technical aspects of PGD-AS, and potential noninvasive embryo selection methods are described. Indications for PGD and possible causes of discordant PGD results between the centers are discussed. The limitations of fluorescence in situ hybridization, and the advantages of the array comparative genomic hybridization are included in this review. Although PGD-AS for patients of advanced maternal age has been shown to improve in vitro fertilization outcomes in some studies, to our knowledge, there is not sufficient evidence to use advanced maternal age as the sole indication for PGD-AS. PGD-AS might be harmful and may not increase the success rates of in vitro fertilization. At the same time PGD, is not recommended for recurrent implantation failure and unexplained recurrent pregnancy loss. Copyright © 2014. Published by Elsevier Taiwan.

  9. Screening for Intimate Partner Violence in Orthopedic Patients: A Comparison of Three Screening Tools

    ERIC Educational Resources Information Center

    Sprague, Sheila; Madden, Kim; Dosanjh, Sonia; Petrisor, Brad; Schemitsch, Emil H.; Bhandari, Mohit

    2012-01-01

    Accurately identifying victims of intimate partner violence (IPV) can be a challenge for clinicians and clinical researchers. Multiple instruments have been developed and validated to identify IPV in patients presenting to health care practitioners, including the Woman Abuse Screening Tool (WAST) and the Partner Violence Screen (PVS). The purpose…

  10. Screening for Intimate Partner Violence in Orthopedic Patients: A Comparison of Three Screening Tools

    ERIC Educational Resources Information Center

    Sprague, Sheila; Madden, Kim; Dosanjh, Sonia; Petrisor, Brad; Schemitsch, Emil H.; Bhandari, Mohit

    2012-01-01

    Accurately identifying victims of intimate partner violence (IPV) can be a challenge for clinicians and clinical researchers. Multiple instruments have been developed and validated to identify IPV in patients presenting to health care practitioners, including the Woman Abuse Screening Tool (WAST) and the Partner Violence Screen (PVS). The purpose…

  11. “This Lifetime Commitment”: Public Conceptions of Disability and Noninvasive Prenatal Genetic Screening

    PubMed Central

    Steinbach, Rosemary J.; Allyse, Megan; Michie, Marsha; Liu, Emily Y.; Cho, Mildred K.

    2016-01-01

    Recently, new noninvasive prenatal genetic screening technologies for Down syndrome and other genetic conditions have become commercially available. Unique characteristics of these screening tests have reignited long-standing concerns about prenatal testing for intellectual and developmental disabilities. We conducted a web-based survey of a sample of the US public to examine how attitudes towards disability inform views of prenatal testing in the context of these rapidly advancing prenatal genetic screening technologies. Regardless of opinion toward disability, the majority of respondents supported both the availability of screening and the decision to continue a pregnancy positive for aneuploidy. Individuals rationalized their support with various conceptions of disability; complications of the expressivist argument and other concerns from the disability literature were manifested in many responses analyzed. PMID:26566970

  12. Screening Magnetic Resonance Imaging Recommendations and Outcomes in Patients at High Risk for Breast Cancer

    PubMed Central

    Ehsani, Sima; Strigel, Roberta M; Pettke, Erica; Wilke, Lee; Tevaarwerk, Amye J; DeMartini, Wendy; Wisinski, Kari B

    2014-01-01

    Objective The purpose of this study was to determine MRI screening recommendations and the subsequent outcomes in women with increased risk for breast cancer evaluated by oncology subspecialists at an academic center. Patients and Methods Patients evaluated between 1/1/2007– 3/1/2011 under diagnosis codes for family history of breast or ovarian cancer, genetic syndromes, lobular carcinoma in situ or atypical hyperplasia were included. Patients with a history of breast cancer were excluded. Retrospective review of prospectively acquired demographics, lifetime risk of breast cancer and screening recommendations were obtained from the medical record. Retrospective review of the results of prospectively interpreted breast imaging examinations and image-guided biopsies were analyzed. Results 282 women were included. The majority of patients were premenopausal with a median age of 43. Most (69%) were referred due to a family history of breast or ovarian cancers. MRI was recommended for 84% of patients based on a documented lifetime risk > 20%. Most women referred for MRI screening (88%) were compliant with this recommendation. A total of 299 breast MRI examinations were performed in 146 patients. Biopsy was performed for 32 (11%) exams and 10 cancers were detected for a PPV of 31% (based on biopsy performed) and an overall per exam cancer yield of 3.3%. Three cancers were detected in patients who did not undergo screening MRI. The 13 cancers were Stage 0-II; all patients were without evidence of disease with a median follow-up of 22 months. Conclusion In a cohort of women seen by breast subspecialty providers, screening breast MRI was recommended according to guidelines, and used primarily premenopausal women with a family history or genetic predisposition to breast cancer. Adherence to MRI screening recommendations was high and cancer yield from breast MRI was similar to that in clinical trials. PMID:25789917

  13. Attitudes of cystic fibrosis patients and parents toward carrier screening and related reproductive issues

    PubMed Central

    Janssens, Sandra; Chokoshvilli, Davit; Binst, Carmen; Mahieu, Inge; Henneman, Lidewij; De Paepe, Anne; Borry, Pascal

    2016-01-01

    Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder affecting ~1 in 2500–4000 Caucasians. As most CF patients have no family history of the disorder, carrier screening for CF has the potential to prospectively identify couples at risk of conceiving an affected child. At-risk couples may consequently choose to act on the provided information and take steps to avoid the birth of a child with CF. Although carrier screening is widely believed to enhance reproductive autonomy of prospective parents, the practice also raises important ethical questions. A written questionnaire was administered to adult patients and parents of children with CF with the aim to explore participants' attitudes toward CF carrier screening and related reproductive issues. The study population was recruited from a CF patient registry in Belgium and comprised 111 participants (64 parents, 47 patients aged 16 or older). We found that more than 80% of all participants were in favor of preconception carrier screening for CF. However, some were concerned over potential negative consequences of population-wide CF carrier screening. Regarding future reproductive intentions, 43% of the participants indicated a desire to have children. Among these, preimplantation genetic diagnosis was found to be the most preferred reproductive option, closely followed by spontaneous pregnancy and prenatal diagnosis. Although the findings of our study suggest that patients and parents of children with CF support a population-based carrier screening program for CF, they also highlight some issues deserving particular attention when implementing such a program. PMID:26220700

  14. Attitudes of cystic fibrosis patients and parents toward carrier screening and related reproductive issues.

    PubMed

    Janssens, Sandra; Chokoshvilli, Davit; Binst, Carmen; Mahieu, Inge; Henneman, Lidewij; De Paepe, Anne; Borry, Pascal

    2016-04-01

    Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder affecting ~1 in 2500-4000 Caucasians. As most CF patients have no family history of the disorder, carrier screening for CF has the potential to prospectively identify couples at risk of conceiving an affected child. At-risk couples may consequently choose to act on the provided information and take steps to avoid the birth of a child with CF. Although carrier screening is widely believed to enhance reproductive autonomy of prospective parents, the practice also raises important ethical questions. A written questionnaire was administered to adult patients and parents of children with CF with the aim to explore participants' attitudes toward CF carrier screening and related reproductive issues. The study population was recruited from a CF patient registry in Belgium and comprised 111 participants (64 parents, 47 patients aged 16 or older). We found that more than 80% of all participants were in favor of preconception carrier screening for CF. However, some were concerned over potential negative consequences of population-wide CF carrier screening. Regarding future reproductive intentions, 43% of the participants indicated a desire to have children. Among these, preimplantation genetic diagnosis was found to be the most preferred reproductive option, closely followed by spontaneous pregnancy and prenatal diagnosis. Although the findings of our study suggest that patients and parents of children with CF support a population-based carrier screening program for CF, they also highlight some issues deserving particular attention when implementing such a program.

  15. Embryo selection with preimplantation chromosomal screening in patients with recurrent pregnancy loss.

    PubMed

    Shahine, Lora K; Lathi, Ruth B

    2014-03-01

    Recurrent pregnancy loss (RPL) is a multifactorial disorder which is often challenging for both patients and providers. Guidelines for the evaluation and treatment of patients with RPL include screening for uterine abnormalities, parental chromosomes, and antiphospholipid antibodies, but approximately half of RPL patients remain unexplained. The current recommendation for patients with unexplained RPL is expectant management which offers most patients a 60 to 80% success rate over time. Genetic imbalances in the embryo, including inherited unbalanced translocations and de novo aneuploidy, are frequent causes of miscarriage. Preimplantation genetic screening (PGS) has been proposed as an effective method for selecting viable embryos for transfer that may result lower risk of miscarriage for patients with unexplained RPL and carriers of balanced translocations. The current evidence examining the use of in vitro fertilization with PGS in patients with RPL reveals variable results, due to differences in technologies used and variable patient populations. Newer approaches, which include blastocyst biopsy and the ability to screen for all 24 chromosomes, show the most promise in reducing miscarriage rates. Studies that identify which patients are most likely to benefit from PGS and include live birth rates per initiated cycles are needed before universally recommending this treatment to couples with RPL.

  16. Screening magnetic resonance imaging recommendations and outcomes in patients at high risk for breast cancer.

    PubMed

    Ehsani, Sima; Strigel, Roberta M; Pettke, Erica; Wilke, Lee; Tevaarwerk, Amye J; DeMartini, Wendy B; Wisinski, Kari B

    2015-01-01

    The purpose of this study was to determine magnetic resonance imaging (MRI) screening recommendations and the subsequent outcomes in women with increased risk for breast cancer evaluated by oncology subspecialists at an academic center. Patients evaluated between 1/1/2007 and 3/1/2011 under diagnosis codes for family history of breast or ovarian cancer, genetic syndromes, lobular carcinoma in situ or atypical hyperplasia were included. Patients with a history of breast cancer were excluded. Retrospective review of prospectively acquired demographics, lifetime risk of breast cancer, and screening recommendations were obtained from the medical record. Retrospective review of the results of prospectively interpreted breast imaging examinations and image-guided biopsies were analyzed. 282 women were included. The majority of patients were premenopausal with a median age of 43. Most (69%) were referred due to a family history of breast or ovarian cancers. MRI was recommended for 84% of patients based on a documented lifetime risk >20%. Most women referred for MRI screening (88%) were compliant with this recommendation. A total of 299 breast MRI examinations were performed in 146 patients. Biopsy was performed for 32 (11%) exams and 10 cancers were detected for a positive predictive value (PPV) of 31% (based on biopsy performed) and an overall per exam cancer yield of 3.3%. Three cancers were detected in patients who did not undergo screening MRI. The 13 cancers were Stage 0-II; all patients were without evidence of disease with a median follow-up of 22 months. In a cohort of women seen by breast subspecialty providers, screening breast MRI was recommended according to guidelines, and used primarily in premenopausal women with a family history or genetic predisposition to breast cancer. Adherence to MRI screening recommendations was high and cancer yield from breast MRI was similar to that in clinical trials. © 2015 Wiley Periodicals, Inc.

  17. Pathways and barriers to genetic testing and screening: Molecular genetics meets the high-risk family. Final report

    SciTech Connect

    Duster, T.

    1998-11-01

    The proliferation of genetic screening and testing is requiring increasing numbers of Americans to integrate genetic knowledge and interventions into their family life and personal experience. This study examines the social processes that occur as families at risk for two of the most common autosomal recessive diseases, sickle cell disease (SC) and cystic fibrosis (CF), encounter genetic testing. Each of these diseases is found primarily in a different ethnic/racial group (CF in Americans of North European descent and SC in Americans of West African descent). This has permitted them to have a certain additional lens on the role of culture in integrating genetic testing into family life and reproductive planning. A third type of genetic disorder, the thalassemias was added to the sample in order to extent the comparative frame and to include other ethnic and racial groups.

  18. Genetic screening for gynecological cancer: where are we heading?

    PubMed

    Manchanda, Ranjit; Jacobs, Ian

    2016-01-01

    The landscape of cancer genetics in gynecological oncology is rapidly changing. The traditional family history-based approach has limitations and misses >50% mutation carriers. This is now being replaced by population-based approaches. The need for changing the clinical paradigm from family history-based to population-based BRCA1/BRCA2 testing in Ashkenazi Jews is supported by data that demonstrate population-based BRCA1/BRCA2 testing does not cause psychological harm and is cost effective. This article covers various genetic testing strategies for gynecological cancers, including population-based approaches, panel and direct-to-consumer testing as well as the need for innovative approaches to genetic counseling. Advances in genetic testing technology and computational analytics have facilitated an integrated systems medicine approach, providing increasing potential for population-based genetic testing, risk stratification, and cancer prevention. Genomic information along-with biological/computational tools will be used to deliver predictive, preventive, personalized and participatory (P4) and precision medicine in the future.

  19. Carrier screening for cystic fibrosis in US genetic testing laboratories: a survey of laboratory directors.

    PubMed

    Kaufman, D J; Katsanis, S H; Javitt, G H; Murphy, J A; Scott, J A; Hudson, K L

    2008-10-01

    Initial guidelines for cystic fibrosis (CF) carrier screening were issued in 2001 by the American College of Medical Genetics and the American College of Obstetricians and Gynecologists and updated in 2004. It is unknown how these guidelines have influenced laboratory practice. This study examined the uptake of two components of these guidelines for CF screening in genetic testing laboratories. A survey of directors of US genetic testing laboratories was conducted. Of 190 respondents, 178 answered questions about CF testing. Nearly half (49%) performed some type of DNA testing for CF; most of these (92%) performed CF carrier screening. Ten percent used a 23-mutation panel for CF screening. The results of 5T tests were reported as a reflex test by 79% of laboratories, while 8% always returned 5T results and 7% never returned them. Seven percent of laboratories adopted both guidelines, 80% adopted one of the two guidelines, and 13% had not adopted either recommendation, suggesting that factors other than clinical guidelines may influence laboratories' CF screening practices. Further studies are needed to determine whether the adoption of CF screening guidelines has significant clinical or economic effects on population-based CF screening programs.

  20. Prostate cancer screening using risk stratification based on a multi-state model of genetic variants.

    PubMed

    Yen, Amy Ming-Fang; Auvinen, Anssi; Schleutker, Johanna; Wu, Yi-Ying; Fann, Jean Ching-Yuan; Tammela, Teuvo; Chen, Sam Li-Sheng; Chiu, Sherry Yueh-Hsia; Chen, Hsiu-Hsi

    2015-06-01

    Risk-stratified screening for prostate cancer (PCa) with prostate-specific antigen (PSA) testing incorporating genetic variants has received some attention but has been scarcely investigated. We developed a model to stratify the Finnish population by different risk profiles related to genetic variants to optimize the screening policy. Data from the Finnish randomized controlled trial on screening for PCa with PSA testing were used to estimate a six-state Markov model of disease progression. Blood samples from Finnish men were used to assess the risk of PCa related to three genetic variants (rs4242382, rs138213197, and rs200331695). A risk score-based approach combined with a series of computer simulation models was applied to optimize individual screening policies. The 10-year risk of having progressive prostate cancer detected ranged from 43% in the top 5% risk group to approximately 11% in the bottom half of the population. Using the median group, with screening every four years beginning at 55 years-old, as the reference group, the recommended age beginning screening was approximately 47 years-old for the top 5% risk group and 55 years-old for those in the lower 60% risk group. The recommended interscreening interval has been shortened for individuals in the high risk group. The increased availability of genomic information allows the proposed multistate model to be more discriminating with respect to risk stratification and the suggested screening policy, particularly for the lowest risk groups-. -- A multi-state genetic variant-based model was developed for further application to population risk stratification to optimize the interscreening interval and the age at which to begin screening for PSA. A small sub-group of the population is likely to benefit from more intensive screening with early start and short interval, while half of the population is unlikely to benefit from such protocol (compared with four-year interval after age 55 years). © 2015 Wiley

  1. Increasing live birth rate by preimplantation genetic screening of pooled polar bodies using array comparative genomic hybridization.

    PubMed

    Feichtinger, Michael; Stopp, Tina; Göbl, Christian; Feichtinger, Elisabeth; Vaccari, Enrico; Mädel, Ulrike; Laccone, Franco; Stroh-Weigert, Monika; Hengstschläger, Markus; Feichtinger, Wilfried; Neesen, Jürgen

    2015-01-01

    Meiotic errors during oocyte maturation are considered the major contributors to embryonic aneuploidy and failures in human IVF treatment. Various technologies have been developed to screen polar bodies, blastomeres and trophectoderm cells for chromosomal aberrations. Array-CGH analysis using bacterial artificial chromosome (BAC) arrays is widely applied for preimplantation genetic diagnosis (PGD) using single cells. Recently, an increase in the pregnancy rate has been demonstrated using array-CGH to evaluate trophectoderm cells. However, in some countries, the analysis of embryonic cells is restricted by law. Therefore, we used BAC array-CGH to assess the impact of polar body analysis on the live birth rate. A disadvantage of polar body aneuploidy screening is the necessity of the analysis of both the first and second polar bodies, resulting in increases in costs for the patient and complex data interpretation. Aneuploidy screening results may sometimes be ambiguous if the first and second polar bodies show reciprocal chromosomal aberrations. To overcome this disadvantage, we tested a strategy involving the pooling of DNA from both polar bodies before DNA amplification. We retrospectively studied 351 patients, of whom 111 underwent polar body array-CGH before embryo transfer. In the group receiving pooled polar body array-CGH (aCGH) analysis, 110 embryos were transferred, and 29 babies were born, corresponding to live birth rates of 26.4% per embryo and 35.7% per patient. In contrast, in the control group, the IVF treatment was performed without preimplantation genetic screening (PGS). For this group, 403 embryos were transferred, and 60 babies were born, resulting in live birth rates of 14.9% per embryo and 22.7% per patient. In conclusion, our data show that in the aCGH group, the use of aneuploidy screening resulted in a significantly higher live birth rate compared with the control group, supporting the benefit of PGS for IVF couples in addition to the

  2. Danish retinoblastoma patients 1943-2013 - genetic testing and clinical implications.

    PubMed

    Gregersen, Pernille A; Urbak, Steen F; Funding, Mikkel; Overgaard, Jens; Jensen, Uffe B; Alsner, Jan

    2016-01-01

    In heritable retinoblastoma there is a 50% risk of transmitting the RB1 mutation, and offspring carriers have more than 90% risk of developing retinoblastoma. Today, all newly diagnosed retinoblastoma patients in Denmark are screened for mutations in RB1, as opposed to only a minority of patients diagnosed before DNA testing was offered. Knowledge of heredity increases the chance of early diagnosis in offspring, leading to improved prognosis. We present data from the Danish retinoblastoma patients that emphasize the need for genetic counseling and RB1 screening in all untested retinoblastoma survivors. Data are extracted from The Danish Ocular Oncology Group Database, a national population database containing data on all Danish retinoblastoma patients since 1943. In total 323 retinoblastoma patients have been diagnosed between 1943 and 2013. Since 1963, the rate has been stable around 1 per 14 000 live births with 95% of the patients surviving their retinoblastoma. Stratifying data on the time of diagnosis and status of genetic testing, the number of screened patients gradually increased from 5% in the beginning of the period to 96% in the last five-year period. A cohort of 181 retinoblastoma survivors with sporadic disease (15% heritable) did not receive genetic testing. Since the introduction of routine testing, one of 14 sporadic unilateral patients tested (7%) has been identified with a germline mutation. Before routine testing, five additional sporadic unilateral patients have been identified as heritable. Only a minority of Danish retinoblastoma patients diagnosed before routine genetic testing was offered have been RB1 screened. To counsel the remaining untested patients and their families sufficiently regarding the risk to offspring and elevated risk of second primary cancers, we recommend information and access to genetic counseling and RB1 screening. This has ethical, psychological and possible economic consequences, and should be handled with caution.

  3. [Screening of peafowl microsatellite primers and analysis of genetic diversity].

    PubMed

    Bao, Wen-Bin; Chen, Guo-Hong; Shu, Jing-Ting; Xu, Qi; Li, Hui-Fang

    2006-10-01

    The applicability of chicken microsatellite primers to peafowl population was analyzed in the present paper, and the results showed 14 of 29 pairs of microsatellite primers from chicken could amplify peafowl DNA and produce specific allele patterns. A mean of 1.71 alleles was found for each locus. Seven pairs were highly polymorphic, and MCW0080 and MCW0098 were ideal markers for peafowl. Genetic diversity analysis within and between the green peafowl and the blue peafowl populations demonstrated that the expected heterozygosity of two peafowl populations were 0.2482 and 0.2744, respectively. The inbreeding index (FST), Reynolds' genetic distance and gene flow between the two populations were 0.078, 0.0603 and 3.896 respectively. These results indicate that the heterozygosity and the genetic diversity of these two peafowl populations were very low, and suggest a tendency towards intermixing.

  4. [Assessment of a malnutrition screening tool in cancer patients].

    PubMed

    Gómez Candela, C; Olivar Roldán, J; García, M; Marín, M; Madero, R; Pérez-Portabella, C; Planás, M; Mokoroa, A; Pereyra, F; Martín Palmero, A

    2010-01-01

    40-80% of cancer patients suffer from diverse degrees of malnutrition, depending on tumor subtype, location and staging and treatment strategy. Malnutrition is associated with increased morbidity and mortality in cancer patients. Both the high prevalence and prognostic significance of malnutrition imply the need for accurate malnutrition screening in cancer patients, which could select those patients at risk of nutritional derangements who would benefit from nutritional therapy. Patient-generated subjective global screening (VSG-GP) remains the reference malnutrition screening method, but its complexity and training requirements prevent wider applicability by oncologists. Thus, easier, more clinic-based malnutrition screening tools are required for cancer patients. In this article we propose a basic screening tool based on three items: weight loss, changes in physical activity and decrease in food intake. Two affirmative responses out of the three questions is considered as a positive response, and would prompt expert nutritional assessment. Our screening interview showed positive correlation with VSG-GP (ROC 0.85, p<0.001) and allowed for a rapid and accurate identification of patients with cancer-related malnutrition.

  5. Cost-effectiveness of a school-based Tay-Sachs and cystic fibrosis genetic carrier screening program.

    PubMed

    Warren, Emma; Anderson, Rob; Proos, Anné L; Burnett, Leslie B; Barlow-Stewart, Kris; Hall, Jane

    2005-09-01

    To explore the cost-effectiveness of school-based multi-disease genetic carrier screening. Decision analysis of the cost-effectiveness of a school-based Tay-Sachs disease and cystic fibrosis genetic carrier screening program, relative to no screening. Data relating to ethnicity profile, test-accepting behavior, and screening program cost were sourced from an existing program in Sydney, Australia. Compared to no screening, the incremental cost-effectiveness of the screening program is A dollar 5,834 per additional carrier detected. This cost-effectiveness ratio is most sensitive to changes in genetic test accuracy, and the cost of laboratory assays. The results imply a cost per affected birth avoided of approximately A dollar 530,000 (approximately US dollar 371,000). This preconceptional genetic carrier screening program offers comparable cost-effectiveness to prenatal screening programs for cystic fibrosis.

  6. Genetic screening technology: ethical issues in access to tests by employers and health insurance committees.

    PubMed

    Faden, R R; Kass, N E

    1993-01-01

    Whereas the introduction of new technologies previously has raised the ethical question of who ought to have access to a new procedure or device, genetic testing technology raises the new ethical question of to whom access to a new technology ought to be limited. In this article we discuss the implications of employers and private health insurance companies having access to genetic testing technology. Although there may be legitimate business interests in allowing employers and insurers to conduct genetic screening, there are other valid societal interests in regulating or limiting the use of this technology by third parties. Public policy developed in the area of new genetic technology must reflect such interests.

  7. Considering Culture in Physician– Patient Communication During Colorectal Cancer Screening

    PubMed Central

    Gao, Ge; Burke, Nancy; Somkin, Carol P.; Pasick, Rena

    2010-01-01

    Racial and ethnic disparities exist in both incidence and stage detection of colorectal cancer (CRC). We hypothesized that cultural practices (i.e., communication norms and expectations) influence patients’ and their physicians’ understanding and talk about CRC screening. We examined 44 videotaped observations of clinic visits that included a CRC screening recommendation and transcripts from semistructured interviews that doctors and patients separately completed following the visit. We found that interpersonal relationship themes such as power distance, trust, directness/indirectness, and an ability to listen, as well as personal health beliefs, emerged as affecting patients’ definitions of provider–patient effective communication. In addition, we found that in discordant physician–patient interactions (when each is from a different ethnic group), physicians did not solicit or address cultural barriers to CRC screening and patients did not volunteer culture-related concerns regarding CRC screening. PMID:19363141

  8. Screening for prostate cancer. How can patients give informed consent?

    PubMed Central

    Marshall, K. G.

    1993-01-01

    Many urologists in North America are increasingly enthusiastic about prostatic cancer screening. Annual digital rectal examination is almost universally endorsed, and prostate-specific antigen testing is favored by most. But doctors really should not screen by either method without patients' informed consent. However, the information required for informed consent is complex and contradictory, difficult for physicians to give and for patients to absorb. PMID:7505673

  9. Moderating effects of autism on parent views of genetic screening for aggression.

    PubMed

    May, Michael E; Brandt, Rachel C; Bohannan, Joseph K

    2012-10-01

    Advances in gene-environment interaction research have revealed genes that are associated with aggression. However, little is known about parent perceptions of genetic screening for behavioral symptoms like aggression as opposed to diagnosing disabilities. These perceptions may influence future research endeavors involving genetic linkage studies to behavior, including proactive approaches for parents to avoid events leading to aggression. The purpose of this study was to solicit the perspectives of parents who have children with autism about screening for genes associated with aggression, compared to responses from those who have children without disabilities and those planning to have children. Parents of children with autism were more likely to support screening and the use of the results to seek treatment if necessary. Results are discussed in the context of surveillance screening and systematic early intervention for behavioral symptoms related to autism. The results may provide insight for clincians, researchers, policymakers, and advocacy groups related to diagnosing and treating aggression in people with autism.

  10. A methodological overview on molecular preimplantation genetic diagnosis and screening: a genomic future?

    PubMed

    Vendrell, Xavier; Bautista-Llácer, Rosa

    2012-12-01

    The genetic diagnosis and screening of preimplantation embryos generated by assisted reproduction technology has been consolidated in the prenatal care framework. The rapid evolution of DNA technologies is tending to molecular approaches. Our intention is to present a detailed methodological view, showing different diagnostic strategies based on molecular techniques that are currently applied in preimplantation genetic diagnosis. The amount of DNA from one single, or a few cells, obtained by embryo biopsy is a limiting factor for the molecular analysis. In this sense, genetic laboratories have developed molecular protocols considering this restrictive condition. Nevertheless, the development of whole-genome amplification methods has allowed preimplantation genetic diagnosis for two or more indications simultaneously, like the selection of histocompatible embryos plus detection of monogenic diseases or aneuploidies. Moreover, molecular techniques have permitted preimplantation genetic screening to progress, by implementing microarray-based comparative genome hybridization. Finally, a future view of the embryo-genetics field based on molecular advances is proposed. The normalization, cost-effectiveness analysis, and new technological tools are the next topics for preimplantation genetic diagnosis and screening. Concomitantly, these additions to assisted reproduction technologies could have a positive effect on the schedules of preimplantation studies.

  11. Physician–Patient Communication about Colorectal Cancer Screening

    PubMed Central

    Wolf, Michael S.; Baker, David W.

    2007-01-01

    Background Despite the documented benefits of colorectal cancer screening, patient participation rates remain low. Physician recommendation has been identified as a significant predictor of screening completion. Objective The aim of this study is to investigate how primary care physicians perceive colorectal cancer screening communication tasks, as well as to explore the form and content of actual screening discussions. Design The research design includes a mailed physician survey and a separate observational study in a sample of videotaped medical encounters. Participants and Data Sources The participants were 270 primary care physicians who completed a mailed questionnaire (57.9% response rate) and 18 physician–patient encounters that included discussions of colorectal cancer screening. Measurement The questionnaire focused on perceived importance and accomplishment of communication tasks relevant to colorectal cancer screening. Two of the authors reviewed transcripts of videotaped physician encounters to determine whether the same communication tasks assessed in the survey were accomplished. Interrater reliability was high across all of the mutually exclusive coding categories (Kappa > .90). Results Physicians rated colonoscopy as the most important screening option to discuss; self-reports indicate that colonoscopy (84.8%) is more frequently mentioned than fecal occult blood test (FOBT; 49.4%), flexible sigmoidoscopy (34.1%), or computed tomography (CT) imaging (18.1%). Explaining benefits and risks, describing test procedure and frequency, eliciting patient preferences, and making a plan for screening were all viewed as very important. Self-reported accomplishment of these communication tasks was considerably higher than that observed in our separate videotape sample. Conclusion Most physicians recognize and espouse the importance of recommending colorectal cancer screening to eligible patients. However, findings from both the physician survey and

  12. Screening for asymptomatic cardiovascular disease in Arab patients with diabetes.

    PubMed

    Elsharawy, M A; Al-Elq, A H; Alkhadra, A H; Moghazy, K M; Elsaid, A S

    2011-02-01

    Diabetes mellitus is a major risk factor for atherosclerosis and accordingly increased morbidity and mortality. This study aimed at screening high risk diabetic patients for atherosclerosis in different arterial territories. All high risk asymptomatic patients attending the diabetic clinic, King Fahd Hospital of the University, Saudi Arabia were invited to be screened for peripheral arterial disease (PAD), extra-cranial cerebrovascular disease (CVD) and coronary artery disease (CAD) over one year. All participants underwent measurement of ankle brachial pressure index, carotid Duplex scan and exercise electrocardiography (ECG). All patients underwent evaluation of conventional risk factors for atherosclerosis One hundred and sixty nine patients were invited to be screened. Of these 138 (82%) completed all the screening tests. The mean age was 53.5±7.18 years. Seventy-five (55%) had evidence of subclinical atherosclerosis. In the atherosclerotic group, 24 patients had PAD, 47 had CVD and 30 had CAD. There were significant differences between the atherosclerotic and non-atherosclerotic groups with regard to most risk factors. In age, sex adjusted, the risk of developing atherosclerosis was significantly increased with all risk factors. Dyslipidemia had the highest association (OR 9.7, 95% CI 8.1-10.2) Participation and diagnostic yield of screening for atherosclerosis had satisfactory validity and reliability. Routine screening in high-risk diabetic patients can serve as an effective tool for diagnosis of sub clinical cardiovascular disease and provide strategies to optimize risk reduction.

  13. Familial screening and genetic counselling in hypertrophic cardiomyopathy: the Rotterdam experience

    PubMed Central

    Michels, M.; Hoedemaekers, Y.M.; Kofflard, M.J.; Frohn-Mulder, I.; Dooijes, D.; Majoor-Krakauer, D.; Ten Cate, F.J.

    2007-01-01

    Hypertrophic cardiomyopathy (HCM) is a disease characterised by unexplained left ventricular hypertrophy (LVH) (i.e. LVH in the absence of another cardiac or systemic disease that could produce a similar degree of hypertrophy), electrical instability and sudden death (SD). Germline mutations in genes encoding for sarcomere proteins are found in more than half of the cases of unexplained LVH. The autosomal dominant inherited forms of HCM are characterised by incomplete penetrance and variability in clinical and echocardiographic features, prognosis and therapeutic modalities. The identification of the genetic defect in one of the HCM genes allows accurate presymptomatic detection of mutation carriers in a family. Cardiac evaluation of at-risk relatives enables early diagnosis and identification of those patients at high risk for SD, which can be the first manifestation of the disease in asymptomatic persons. In this article we present our experience with genetic testing and cardiac screening in our HCM population and give an overview of the current literature available on this subject. (Neth Heart J 2007;15:184-9.17612681) PMID:17612681

  14. Preimplantation genetic screening: results of a worldwide web-based survey.

    PubMed

    Weissman, Ariel; Shoham, Gon; Shoham, Zeev; Fishel, Simon; Leong, Milton; Yaron, Yuval

    2017-09-21

    Our objective was to evaluate and characterize the extent and patterns of worldwide usage of preimplantation genetic screening (PGS) among the assisted reproductive technique community. A prospective, web-based questionnaire with questions relating to practices of, and views on, PGS was directed to users and non-users of PGS. A total of 386 IVF units from 70 countries conducting 342,600 IVF cycles annually responded to the survey. A total of 77% of respondents routinely carry out PGS in their clinics for a variety of indications: advanced maternal age (27%), recurrent implantation failure (32%) and recurrent pregnancy loss (31%). Few (6%) offer PGS to all their patients. In most cycles (72%), trophectoderm biopsy is carried out and either array-comparative genomic hybridization (59%) or next-generation sequencing (16%) are used for genetic analysis. Only 30% of respondents regard PGS as clearly evidenced-based, and most (84%) believe that more randomized controlled trials are needed to support the use of PGS. Despite ongoing debate and lack of robust evidence, most respondents support the use of PGS, and believe that it may aid in transferring only euploid embryos, thereby reducing miscarriage rates and multiple pregnancies, increasing live birth rates and reducing the risk of aneuploid pregnancies and births. Copyright © 2017. Published by Elsevier Ltd.

  15. Frailty Screening Tools for Elderly Patients Incident to Dialysis.

    PubMed

    van Loon, Ismay N; Goto, Namiko A; Boereboom, Franciscus T J; Bots, Michiel L; Verhaar, Marianne C; Hamaker, Marije E

    2017-07-17

    A geriatric assessment is an appropriate method for identifying frail elderly patients. In CKD, it may contribute to optimize personalized care. However, a geriatric assessment is time consuming. The purpose of our study was to compare easy to apply frailty screening tools with the geriatric assessment in patients eligible for dialysis. A total of 123 patients on incident dialysis ≥65 years old were included <3 weeks before to ≤2 weeks after dialysis initiation, and all underwent a geriatric assessment. Patients with impairment in two or more geriatric domains on the geriatric assessment were considered frail. The diagnostic abilities of six frailty screening tools were compared with the geriatric assessment: the Fried Frailty Index, the Groningen Frailty Indicator, Geriatric8, the Identification of Seniors at Risk, the Hospital Safety Program, and the clinical judgment of the nephrologist. Outcome measures were sensitivity, specificity, positive predictive value, and negative predictive value. In total, 75% of patients were frail according to the geriatric assessment. Sensitivity of frailty screening tools ranged from 48% (Fried Frailty Index) to 88% (Geriatric8). The discriminating features of the clinical judgment were comparable with the other screening tools. The Identification of Seniors at Risk screening tool had the best discriminating abilities, with a sensitivity of 74%, a specificity of 80%, a positive predictive value of 91%, and a negative predictive value of 52%. The negative predictive value was poor for all tools, which means that almost one half of the patients screened as fit (nonfrail) had two or more geriatric impairments on the geriatric assessment. All frailty screening tools are able to detect geriatric impairment in elderly patients eligible for dialysis. However, all applied screening tools, including the judgment of the nephrologist, lack the discriminating abilities to adequately rule out frailty compared with a geriatric assessment

  16. The future role of genetic screening to detect newborns at risk of childhood-onset hearing loss

    PubMed Central

    2013-01-01

    Objective: To explore the future potential of genetic screening to detect newborns at risk of childhood-onset hearing loss. Design: An expert led discussion of current and future developments in genetic technology and the knowledge base of genetic hearing loss to determine the viability of genetic screening and the implications for screening policy. Results and Discussion: Despite increasing pressure to adopt genetic technologies, a major barrier for genetic screening in hearing loss is the uncertain clinical significance of the identified mutations and their interactions. Only when a reliable estimate of the future risk of hearing loss can be made at a reasonable cost, will genetic screening become viable. Given the speed of technological advancement this may be within the next 10 years. Decision-makers should start to consider how genetic screening could augment current screening programmes as well as the associated data processing and storage requirements. Conclusion: In the interim, we suggest that decision makers consider the benefits of (1) genetically testing all newborns and children with hearing loss, to determine aetiology and to increase knowledge of the genetic causes of hearing loss, and (2) consider screening pregnant women for the m.1555A> G mutation to reduce the risk of aminoglycoside antibiotic-associated hearing loss. PMID:23131088

  17. Advances in the Genetic Screening, Work-up, and Treatment of Pancreatic Cancer.

    PubMed

    Frucht, Harold; Stevens, Peter D.; Fogelman, David R.; Verna, Elizabeth C.; Chen, Johnson; Chabot, John A.; Fine, Robert L.

    2004-10-01

    Familiarity with the updated results in genetic screening and work-up presented here is essential to early diagnosis and possible cure. In the metastatic setting, we most frequently begin with the GTX regimen, consisting of Gemcitabine, Taxotere, and Xeloda. The regimen is based on our laboratory data demonstrating a synergistic increase in cell killing of pancreatic cancer cell lines. The combination takes advantage of the selective cell cycle effects of each of the three drugs. In our initial experience, we have seen a response rate of 40% at metastatic sites and 31% at the primary site after nine cycles of GTX. We are now conducting a formal phase II protocol to confirm these results. The median survival of this group of patients (at least 10.4 months) is as long as, or longer than other currently used regimens. In those patients who do not tolerate GTX or progress despite the regimen, we have found that a regimen of the same three drugs, administered on a different schedule, can produce responses. In the neoadjuvant (unresectable) setting, we treat with GTX initially and then follow with radiation; gemcitabine is used as a radiosensitizer during this treatment. An aggressive surgical approach with a team of surgeons were able to resect for cure 12 of the 16 patients who were initially unresectable; one year survival of these 12 was 100%; 2 year survival was 50%. Future work in this disease should focus on targeted agents such as bevacizumab.

  18. Forward Genetic Screening Using Behavioral Tests in Zebrafish: A Proof of Concept Analysis of Mutants.

    PubMed

    Gerlai, Robert; Poshusta, Tanya L; Rampersad, Mindy; Fernandes, Yohaan; Greenwood, Tammy M; Cousin, Margot A; Klee, Eric W; Clark, Karl J

    2017-01-01

    The zebrafish enjoys several advantages over other model organisms. It is small, easy to maintain, prolific, and numerous genetic tools are available for it. For example, forward genetic screens have allowed investigators to identify important genes potentially involved in a variety of functions from embryogenesis to cancer. However, despite its sophisticated behavioral repertoire, behavioral methods have rarely been utilized in forward genetic screens. Here, we employ a two-tiered strategy, a proof of concept study, to explore the feasibility of behavioral screens. We generated mutant lines using transposon-based insertional mutagenesis, allowing us to bias mutant selection with target genes expressed within the brain. Furthermore, we employed an efficient and fast behavioral pre-selection in which we investigated the locomotory response of 5-day post-fertilization old larval fish to hyperosmotic shock. Based on this assay, we selected five lines for our lower throughput secondary adult behavioral screen. The latter screen utilized tests in which computer animated image presentation and video-tracking-based automated quantification of behavior allowed us to compare heterozygous zebrafish with their wild-type siblings on their responses to a variety of stimuli. We found significant mutation induced adult behavioral alterations in 4 out of the 5 lines analyzed, including changes in response to social or fear inducing stimuli, to handling and novelty, or in habituation to novelty. We discuss the pros and cons of behavioral phenotyping and of the use of different forward genetic methods in biomedical research with zebrafish.

  19. Molecular screening of patients with nonsyndromic hearing loss from Nanjing city of China☆

    PubMed Central

    Lu, Yajie; Dai, Dachun; Chen, Zhibin; Cao, Xin; Bu, Xingkuan; Wei, Qinjun; Xing, Guangqian

    2011-01-01

    Hearing loss is the most frequent sensory disorder involving a multitude of factors, and at least 50% of cases are due to genetic etiology. To further characterize the molecular etiology of hearing loss in the Chinese population, we recruited a total of 135 unrelated patients with nonsyndromic sensorineural hearing loss (NSHL) for mutational screening of GJB2, GJB3, GJB6, SLC26A4, SLC26A5 IVS2-2A>G and mitochondrial 12SrRNA, tRNASer(UCN) by PCR amplification and direct DNA sequencing. The carrier frequencies of deafness-causing mutations in these patients were 35.55% in GJB2, 3.70% in GJB6, 15.56% in SLC26A4 and 8.14% in mitochondrial 12SrRNA, respectively. The results indicate the necessity of genetic screening for mutations of these causative genes in Chinese population with nonsyndromic hearing loss. PMID:23554706

  20. Parents' experiences of newborn screening for genetic susceptibility to type 1 diabetes.

    PubMed

    Kerruish, Nikki J

    2011-06-01

    Advances in genomic medicine have lead to debate about the potential inclusion of genetic tests for susceptibility to common complex disorders in newborn screening programmes. Empirical evidence concerning psychosocial reactions to genetic testing is a crucial component of both ethical debate and policy development, but while there has been much speculation concerning the possible psychosocial impact of screening newborns for genetic susceptibilities, there remains a paucity of data. The aim of the study reported here is to provide some of this missing empirical evidence, using type 1 diabetes as an example of a common disorder with multiple significant genetic contributors to its aetiology. Semi-structured interviews were conducted with 11 parents of babies who had received increased risk results in a study that involved newborn screening for genetic susceptibility to type 1 diabetes. Interpretative phenomenological analysis was used to evaluate the data. The interview data suggest that the probabilistic nature of results of genetic susceptibility tests impacts upon all aspects of parents' psychosocial reactions, resulting in a complex and dynamic process quite different to that described in relation to current newborn screening programmes. While parents generally reported fairly minor levels of concern in response to news of their child's increased genetic risk, these worries frequently recurred, and perception of risk also varied and fluctuated over time. Both individual and contextual factors appeared to interact with the inherent uncertainty of the test result to contribute to the dynamic nature of parental reactions, and their behavioural responses. The implications of these findings for future research and for the debate concerning potential expansion of newborn screening are discussed.

  1. Designing clinical and genetic guidelines of colorectal cancer screening as an effective roadmap for risk management

    PubMed Central

    Zali, Mohammad Reza; Safdari, Reza; Maserat, Elham; Asadzadeh Aghdaei, Hamid

    2016-01-01

    Aim: We aimed to present clinical and genetic guidelines of colorectal cancer screening for risk assessment of populations at risk. Background: National guidelines can be used as a guide for choosing the method of screening for each individual. These guidelines facilitate decision making and support the delivery of cancer screening service. Methods: In the first step, a comparative study was performed by using secondary data extracted from the literature review. Three countries (Canada, Australia and United States) were selected from 25 countries that are member in the International Cancer Screening Network (ICSN). The second step of study was qualitative survey. The study was based on the grounded theory approach. Study tool was semi-structured interview. Interviewing involves asking questions and getting answers from participants. 22 expert’s perspectives about guidelines of colorectal cancer screening were surveyed. Results: Screening program of selected countries was compared. Countries were surveyed by number of risk groups and subgroups, criteria for risk assessment, beginning age, recommendations, screening approaches and intervals. Australia and United States have three risk groups and Canada has two risk groups. Four risk groups were defined in the national guideline, including high risk, increased risk, average and low risk group. The high risk group comprises of 8 subgroups, increased risk group comprises of 3 subgroups and average risk group contain 4 subgroups. Approved clinical criteria for hereditary syndromes and the roadmap of genetic and pathologic survey were designed. Conclusions: Guidelines and pathways have a vital role in the quality improvement of CRC screening program. National guidelines were refined according to the environmental and genetic criteria of colorectal cancer in Iran. These guidelines provide evidence-based recommendations by risk groups. National pathways as a risk assessment tool can evaluate and improve the processes and

  2. Identification of plant stress-responsive determinants in Arabidopsis by large-scale forward genetic screens.

    PubMed

    Koiwa, Hisashi; Bressan, Ray A; Hasegawa, Paul M

    2006-01-01

    All plants sense and adapt to adverse environmental conditions, however, crop plants exhibit less genetic diversity for abiotic stress tolerance than do wild relatives indicating that a genetic basis exists for stress adaptability. Model plant genetic systems and the plethora of molecular genetic resources that are currently available are greatly enhancing our ability to identify abiotic stress-responsive genetic determinants. Forward genetic screens of T-DNA mutagenized Arabidopsis thaliana populations in the genetic background of ecotypes C24(RD29a-LUC) and Col-0 gl1 sos3-1 were carried out to begin an exhaustive search for such determinants. The C24(RD29a-LUC) screens identified mutants with altered salt/osmotic stress sensitivity or mutants with altered expression of the salt/osmotic/cold/ABA-responsive RD29a gene. Also, mutations that alter the NaCl sensitivity of sos3-1 were screened for potential genetic suppressors or enhancers of salt-stress responses mediated by SOS3. In total, more than 250 000 independent insertion lines were screened and greater than 200 individual mutants that exhibited altered stress/ABA responses were recovered. Although several of these mutants have been reported, most have not yet been studied in detail. Notable examples include novel alleles of SOS1 and mutations to genes encoding the STT3a subunit of the oligosaccharyltransferase, syntaxin, RNA polymerase II CTD phosphatases, transcription factors, ABA biosynthetic enzyme, Na+ transporter HKT1, and SUMO E3 ligase. The stress-specific phenotypes of mutations to genes that are involved in many basic cellular functions provide indication of the wide range of control mechanisms in cellular homeostasis that are involved in stress adaptation.

  3. Validation of a semiconductor next-generation sequencing assay for the clinical genetic screening of CFTR.

    PubMed

    Trujillano, Daniel; Weiss, Maximilian E R; Köster, Julia; Papachristos, Efstathios B; Werber, Martin; Kandaswamy, Krishna Kumar; Marais, Anett; Eichler, Sabrina; Creed, Jenny; Baysal, Erol; Jaber, Iqbal Yousuf; Mehaney, Dina Ahmed; Farra, Chantal; Rolfs, Arndt

    2015-09-01

    Genetic testing for cystic fibrosis and CFTR-related disorders mostly relies on laborious molecular tools that use Sanger sequencing to scan for mutations in the CFTR gene. We have explored a more efficient genetic screening strategy based on next-generation sequencing (NGS) of the CFTR gene. We validated this approach in a cohort of 177 patients with previously known CFTR mutations and polymorphisms. Genomic DNA was amplified using the Ion AmpliSeq™ CFTR panel. The DNA libraries were pooled, barcoded, and sequenced using an Ion Torrent PGM sequencer. The combination of different robust bioinformatics tools allowed us to detect previously known pathogenic mutations and polymorphisms in the 177 samples, without detecting spurious pathogenic calls. In summary, the assay achieves a sensitivity of 94.45% (95% CI: 92% to 96.9%), with a specificity of detecting nonvariant sites from the CFTR reference sequence of 100% (95% CI: 100% to 100%), a positive predictive value of 100% (95% CI: 100% to 100%), and a negative predictive value of 99.99% (95% CI: 99.99% to 100%). In addition, we describe the observed allelic frequencies of 94 unique definitely and likely pathogenic, uncertain, and neutral CFTR variants, some of them not previously annotated in the public databases. Strikingly, a seven exon spanning deletion as well as several more technically challenging variants such as pathogenic poly-thymidine-guanine and poly-thymidine (poly-TG-T) tracts were also detected. Targeted NGS is ready to substitute classical molecular methods to perform genetic testing on the CFTR gene.

  4. Educational outcomes of a workplace screening program for genetic susceptibility to hemochromatosis.

    PubMed

    Nisselle, A E; Collins, V R; Gason, A A; Flouris, A; Delatycki, M B; Allen, K J; Aitken, M A; Metcalfe, S A

    2006-02-01

    Education is an essential component of a genetic screening program. Knowledge outcomes were measured after large-scale workplace education and screening for genetic susceptibility to hereditary hemochromatosis. The aim was to assess knowledge of concepts presented, impact of mode of delivery, and knowledge retention. Education in a group setting was delivered via oral or video presentation and knowledge assessed using self-administered questionnaires at baseline, 1 month, and 12 months. Over 60% of 11 679 participants correctly answered all questions at baseline, scoring higher with clinical concepts (disease etiology and treatment) than genetic concepts (penetrance and genetic heterogeneity). Revising the education program significantly increased correct responses for etiology (p < 0.002), whilst modifying the knowledge assessment tool significantly increased correct responses for etiology (p < 0.001) and gene penetrance (p < 0.001). For three of the four concepts assessed, use of video was as effective as oral presentation for knowledge outcomes. A significantly higher proportion of those at increased risk of disease (n = 44) responded correctly at 12 months than did controls (n = 82; p = 0.011 for etiology, p = 0.002 for treatment and p = 0.003 for penetrance). Hence, genetic screening can be successfully offered in a group workplace setting, with participants remembering clinical concepts better than genetic concepts up to 1 year later.

  5. Medical and lay attitudes towards genetic screening and testing in Finland.

    PubMed

    Toiviainen, Hanna; Jallinoja, Piia; Aro, Arja R; Hemminki, Elina

    2003-08-01

    The purpose of this study was to compare physicians', midwives' and lay people's attitudes towards genetic screening and testing to find out whether medical education and experience influence attitudes of genetic screening and testing. The study was based on comparison of answers to joint questions in three different cross-sectional postal surveys between October 1996 and April 1998 in Finland. Target groups were physicians (study base n=772, response rate 74%, including gynaecologists, paediatricians, general practitioners and clinical geneticists), midwives and public health nurses (collectively referred to as midwives in the following; n=800, response rate 79%), and lay people (n=2000, response rate 62%). Midwives were more worried about the consequences of genetic testing and stressed the autonomy of the customer more strongly than lay people did. Furthermore, professionals considered that lay peoples' expectations as regards to genetic testing are too high. Having more medical education was related to having less 'cannot say' and missing responses. Our results do not suggest that major conflicts about the direction of genetic testing and screening would arise in near future. However, different positions and interests should be considered. Reporting in public about new prospects and developments in medical genetics should pay more attention also to concerns for balancing promises and drawbacks.

  6. A Forward Genetic Screening for Prostate Cancer Progression Genes

    DTIC Science & Technology

    2012-10-01

    melanoma. Nature 436, 117‐122 (2005). 26. J.C. Cronin et al. Frequent mutations in the MITF pathway in melanoma.  Pigment   Cell Melanoma Res. 22, 435‐444... bacterial genetics. J Mol Biol 116: 125–159. 3. Ding S, Wu X, Li G, Han M, Zhuang Y, et al. (2005) Efficient transposition of the piggyBac (PB) transposon

  7. Screening for genetic disorders: therapeutic abortion and IVF.

    PubMed

    Michael, M; Buckle, S

    1990-03-01

    This paper examines a proposal to make use of IVF techniques to provide an alternative to therapeutic abortion of fetuses with genetic abnormalities. We begin by describing the proposed procedure, and then show that, considered in itself, it is morally on a par with therapeutic abortion. However, once the wider practical implications are brought into view, the proposed new procedure loses its initial appeal. The pros and cons are not sufficiently clear-cut entirely to rule out the IVF procedure, so the paper concludes by indicating some further complications which may follow, should the procedure come to be adopted.

  8. Screening for fall risk in patients with haemophilia.

    PubMed

    Flaherty, L M; Josephson, N C

    2013-05-01

    Many risk factors for falls identified in the general population are found in patients with haemophilia. Furthermore, fall risk increases with age and patients with haemophilia are increasingly entering the over 65 age group. After a fall occurs, there are often behavioural changes that have significant health consequences and further increase fall risk. Fall risk can be quickly assessed in the clinical setting with specific questions in the medical history and by a variety of performance-based screening tools. Identification of fall risk enables early intervention, thereby preventing injury and fear of physical activity, both of which have been associated with falling and may carry an increased risk in patients with haemophilia. Review of the existing literature on assessment of fall risk reveals the importance of screening in the clinical setting, which is commonly done via a fall history and performance-based assessment tools. Selecting appropriate fall risk screening tools is an important step in identifying and providing optimal interventions for those at risk. Assessments of fall history, fear of falling, gait velocity, gait variability and vestibular dysfunction are suggested as screening tools for patients with haemophilia. Additional research is needed to determine the optimal screening, evaluation and treatment techniques for these patients. The longitudinal physical therapy care provided by Haemophilia Treatment Centres presents a unique opportunity for instituting measures that will reduce the incidence of falling in patients with haemophilia.

  9. Screening for anxiety disorders in patients with coronary artery disease

    PubMed Central

    2013-01-01

    Background Anxiety disorders are prevalent and associated with poor prognosis in patients with coronary artery disease (CAD). However, studies examining screening of anxiety disorders in CAD patients are lacking. In the present study we evaluated the prevalence of anxiety disorders in patients with CAD and diagnostic utility of self-rating scales for screening of anxiety disorders. Methods Five-hundred and twenty-three CAD patients not receiving psychotropic treatments at initiation of rehabilitation program completed self-rating scales (Hospital Anxiety and Depression Scale or HADS; Spielberger State-Anxiety Inventory or SSAI; and Spielberger Trait-Anxiety Inventory or STAI) and were interviewed for generalized anxiety disorder (GAD), social phobia, panic disorder and agoraphobia (Mini-International Neuropsychiatric Interview or MINI). Results Thirty-eight (7%) patients were diagnosed with anxiety disorder(s), including GAD (5%), social phobia (2%), agoraphobia (1%) and panic disorder (1%). Areas under the ROC curve of the HADS Anxiety subscale (HADS-A), STAI and SSAI for screening of any anxiety disorder were .81, .80 and .72, respectively. Optimal cut-off values for screening of any anxiety disorders were ≥8 for the HADS-A (sensitivity = 82%; specificity = 76%; and positive predictive value (PPV) = 21%); ≥45 for the STAI (sensitivity = 89%; specificity = 56%; and PPV = 14%); and ≥40 for the SSAI (sensitivity = 84%; specificity = 55%; PPV = 13%). In a subgroup of patients (n = 340) scoring below the optimal major depressive disorder screening cut-off value of HADS-Depression subscale (score <5), the HADS-A, STAI and SSAI had moderate-high sensitivity (range from 69% to 89%) and low PPVs (≤22%) for GAD and any anxiety disorders. Conclusions Anxiety disorders are prevalent in CAD patients but can be reliably identified using self-rating scales. Anxiety self-rating scales had comparable sensitivities but the HADS-A had

  10. Screening for anxiety disorders in patients with coronary artery disease.

    PubMed

    Bunevicius, Adomas; Staniute, Margarita; Brozaitiene, Julija; Pop, Victor J M; Neverauskas, Julius; Bunevicius, Robertas

    2013-03-11

    Anxiety disorders are prevalent and associated with poor prognosis in patients with coronary artery disease (CAD). However, studies examining screening of anxiety disorders in CAD patients are lacking. In the present study we evaluated the prevalence of anxiety disorders in patients with CAD and diagnostic utility of self-rating scales for screening of anxiety disorders. Five-hundred and twenty-three CAD patients not receiving psychotropic treatments at initiation of rehabilitation program completed self-rating scales (Hospital Anxiety and Depression Scale or HADS; Spielberger State-Anxiety Inventory or SSAI; and Spielberger Trait-Anxiety Inventory or STAI) and were interviewed for generalized anxiety disorder (GAD), social phobia, panic disorder and agoraphobia (Mini-International Neuropsychiatric Interview or MINI). Thirty-eight (7%) patients were diagnosed with anxiety disorder(s), including GAD (5%), social phobia (2%), agoraphobia (1%) and panic disorder (1%). Areas under the ROC curve of the HADS Anxiety subscale (HADS-A), STAI and SSAI for screening of any anxiety disorder were .81, .80 and .72, respectively. Optimal cut-off values for screening of any anxiety disorders were ≥ 8 for the HADS-A (sensitivity = 82%; specificity = 76%; and positive predictive value (PPV) = 21%); ≥ 45 for the STAI (sensitivity = 89%; specificity = 56%; and PPV = 14%); and ≥ 40 for the SSAI (sensitivity = 84%; specificity = 55%; PPV = 13%). In a subgroup of patients (n = 340) scoring below the optimal major depressive disorder screening cut-off value of HADS-Depression subscale (score <5), the HADS-A, STAI and SSAI had moderate-high sensitivity (range from 69% to 89%) and low PPVs (≤ 22%) for GAD and any anxiety disorders. Anxiety disorders are prevalent in CAD patients but can be reliably identified using self-rating scales. Anxiety self-rating scales had comparable sensitivities but the HADS-A had greater specificity and PPV when compared to the STAI and SSAI for

  11. Patient reported outcomes and patient empowerment in clinical genetics services.

    PubMed

    McAllister, M; Dearing, A

    2015-08-01

    Evaluation of clinical genetics services (CGS), including genetic counseling and genetic testing, has been problematic. Patient mortality and morbidity are unlikely to be directly improved by interventions offered in CGS. Patient-reported outcomes (PROs) are not routinely measured in CGS evaluation, but this may change as patient-reported outcome measures (PROMs) become a key part of how healthcare services are managed and funded across the world. However, there is no clear consensus about which PROMs are most useful for CGS evaluation. This review summarizes the published research on how PROs from CGS have been measured and how patients may benefit from using those services, with a focus on patient empowerment. Many patient benefits (PROs) identified repeatedly in the research literature can be re-interpreted within a patient empowerment framework. Other important PROs identified include family functioning, social functioning, altruism, sense of purpose, enabling development of future research and treatment/participating in research. Well-validated measures are available to capture (dimensions of) patient empowerment. Although generic measures of family functioning are available, suitable measures capturing social functioning, development of future treatments, and altruism were not identified in this review. Patient empowerment provides one useful approach to measuring PROs from CGS.

  12. Diabetes Screening at the Periodontal Visit: Patient and Provider Experiences with Two Screening Approaches

    PubMed Central

    Rosedale, Mary T.; Strauss, Shiela M.

    2012-01-01

    Background This study examined patient and dental provider experiences during the periodontal visit of a novel diabetes screening approach using gingival crevicular blood (GCB) compared with finger stick blood (FSB) for hemoglobin A1c (HbA1c). Methods At a large Periodontics and Implant clinic, FSB samples from 120 patients and GCB samples from 102 of these patients were collected on special blood collection cards and sent to a laboratory for HbA1c testing, with test results sent to the patients from the laboratory. Quantitative and qualitative data collection and analyses of patients and providers were conducted. Results Quantitative and qualitative data support the feasibility and acceptability of the novel approach described. Themes that arose from the interviews with providers and patients include “a good chance to check,” “patient choice,” “FSB versus GCB testing,” and “a new way of interacting and viewing the dental visit.” Conclusions Periodontal patients and dental providers believe that the dental visit is an opportune site for diabetes screening and generally prefer GCB to FSB collection. GCB testing is well-tolerated, convenient and acceptable to patients and reduces time and liability obstacles for dental providers to conduct diabetes screening. PMID:22284167

  13. Impact of human genome initiative-derived technology on genetic testing, screening and counseling: Cultural, ethical and legal issues

    SciTech Connect

    Trottier, R.W.; Hodgin, F.C.; Imara, M.; Phoenix, D.; Lybrook, S. . School of Medicine); Crandall, L.A.; Moseley, R.E.; Armotrading, D. . Coll. of Medicine)

    1993-01-01

    Genetic medical services provided by the Georgia Division of Public Health in two northern and two central districts are compared to services provided in a district in which a tertiary care facility is located. Genetics outreach public health nurses play key roles in Georgia's system of Children's Health Services Genetics Program, including significant roles as counselors and information sources on special needs social services and support organizations. Unique features of individual health districts, (e.g., the changing face of some rural communities in ethnocultural diversity and socioeconomic character), present new challenges to current and future genetics services delivery. Preparedness as to educational needs of both health professionals and the lay population is of foremost concern in light of the ever expanding knowledge and technology in medical genetics. Perspectives on genetics and an overview of services offered by a local private sector counselor are included for comparison to state supported services. The nature of the interactions which transpire between private and public genetic services resources in Georgia will be described. A special focus of this research includes issues associated with sickle cell disease newborn screening service delivery process in Georgia, with particular attention paid to patient follow-up and transition to primary care. Of particular interest to this focus is the problem of loss to follow-up in the current system. Critical factors in education and counseling of sickle cell patients and the expectations of expanding roles of primary care physicians are discussed. The Florida approach to the delivery of genetic services contrasts to the Georgia model by placing more emphasis on a consultant-specialist team approach.

  14. Dehydroepiandrosterone (DHEA) reduces embryo aneuploidy: direct evidence from preimplantation genetic screening (PGS).

    PubMed

    Gleicher, Norbert; Weghofer, Andrea; Barad, David H

    2010-11-10

    Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances in women with diminished ovarian reserve (DOR), and to reduce miscarriage rates by 50-80%. Such an effect is mathematically inconceivable without beneficial effects on embryo ploidy. This study, therefore, assesses effects of DHEA on embryo aneuploidy. In a 1:2, matched case control study 22 consecutive women with DOR, supplemented with DHEA, underwent preimplantation genetic screening (PGS) of embryos during in vitro fertilization (IVF) cycles. Each was matched by patient age and time period of IVF with two control IVF cycles without DHEA supplementation (n = 44). PGS was performed for chromosomes X, Y, 13, 16, 18, 21 and 22, and involved determination of numbers and percentages of aneuploid embryos. DHEA supplementation to a significant degree reduced number (P = 0.029) and percentages (P < 0.001) of aneuploid embryos, adjusted for relevant covariates. Short term supplementation (4-12 weeks) resulted in greatest reduction in aneuploidy (21.6%, 95% CI -2.871-46.031). Beneficial DHEA effects on DOR patients, at least partially, are the likely consequence of lower embryo aneuploidy. DHEA supplementation also deserves investigation in older fertile women, attempting to conceive, where a similar effect, potentially, could positively affect public health.

  15. Lung cancer screening in patients with chronic obstructive pulmonary disease.

    PubMed

    Gonzalez, Jessica; Marín, Marta; Sánchez-Salcedo, Pablo; Zulueta, Javier J

    2016-04-01

    Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low-dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emphysema and chronic bronchitis, have been associated with increased lung cancer risk. Several epidemiological studies, including lung cancer screening trials, have found a 2- to 4-fold increase in lung cancer risk in patients with COPD when compared to individuals without airflow obstruction. Part of the risk attributed to airflow obstruction appears to be derived from the presence of radiographic emphysema. The latter has proven to be an important lung cancer risk factor in smokers without airflow obstruction and even in never smokers. This evidence supports the idea of including patients with COPD and/or emphysema in lung cancer screening programs. There is evidence that lung cancer screening in this population is effective and can potentially reduce mortality. Specific lung cancer risk scores have been developed for patients with COPD [COPD lung cancer screening score (LUCSS) and COPD-LUCSS-diffusing capacity for carbon monoxide (DLCO)] to identify those at high risk. A multidisciplinary approach for an adequate patient selection, especially of patients with severe disease, is key to maximize benefits and reduce harms from lung cancer screening in this population. Patients with COPD included in lung cancer screening programs could also benefit from other interventions, such as smoking cessation and adequate treatment.

  16. Functional genomics platform for pooled screening and mammalian genetic interaction maps

    PubMed Central

    Kampmann, Martin; Bassik, Michael C.; Weissman, Jonathan S.

    2014-01-01

    Systematic genetic interaction maps in microorganisms are powerful tools for identifying functional relationships between genes and defining the function of uncharacterized genes. We have recently implemented this strategy in mammalian cells as a two-stage approach. First, genes of interest are robustly identified in a pooled genome-wide screen using complex shRNA libraries. Second, phenotypes for all pairwise combinations of hit genes are measured in a double-shRNA screen and used to construct a genetic interaction map. Our protocol allows for rapid pooled screening under various conditions without a requirement for robotics, in contrast to arrayed approaches. Each stage of the protocol can be implemented in ~2 weeks, with additional time for analysis and generation of reagents. We discuss considerations for screen design, and present complete experimental procedures as well as a full computational analysis suite for identification of hits in pooled screens and generation of genetic interaction maps. While the protocols outlined here were developed for our original shRNA-based approach, they can be applied more generally, including to CRISPR-based approaches. PMID:24992097

  17. A rapid chemical-genetic screen utilizing impaired movement phenotypes in C. elegans: Input into genetics of neurodevelopmental disorders.

    PubMed

    Schmeisser, Kathrin; Fardghassemi, Yasmin; Parker, J Alex

    2017-07-01

    Autism spectrum disorder (ASD) is the most common neurodevelopmental disorder with a constantly increasing prevalence. Model organisms may be tools to identify underlying cellular and molecular mechanisms, as well as aid the discovery and development of novel therapeutic approaches. A simple animal such as the nematode Caenorhabditis elegans may provide insights into the extreme complexity of ASD genetics. Despite its potential, using C. elegans in ASD research is a controversial approach and has not yet been used extensively in this context. In this study, we present a screening approach of potential C. elegans mutants as potential ASD models. We screened these mutants for motor-deficiency phenotypes, which can be exploited to study underlying mechanisms of the disorder. Selected motor-deficient mutants were then used in a comprehensive drug screen of over 3900 compounds, including many FDA-approved and natural molecules, that were analyzed for their ability to suppress motility defects caused by ASD-associated gene orthologues. This genetic-chemical approach, i.e. establishing C. elegans models for ASD and screening of a well-characterized compound library, might be a promising first step to understand the mechanisms of how gene variations cause neuronal dysfunction, leading to ASD and other neurological disorders. Positively acting compounds could also be promising candidates for preclinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Plant Chemical Genetics: From Phenotype-Based Screens to Synthetic Biology[OPEN

    PubMed Central

    2017-01-01

    The treatment of a biological system with small molecules to specifically perturb cellular functions is commonly referred to as chemical biology. Small molecules are used commercially as drugs, herbicides, and fungicides in different systems, but in recent years they are increasingly exploited as tools for basic research. For instance, chemical genetics involves the discovery of small-molecule effectors of various cellular functions through screens of compound libraries. Whereas the drug discovery field has largely been driven by target-based screening approaches followed by drug optimization, chemical genetics in plant systems tends to be fueled by more general phenotype-based screens, opening the possibility to identify a wide range of small molecules that are not necessarily directly linked to the process of interest. Here, we provide an overview of the current progress in chemical genetics in plants, with a focus on the discoveries regarding small molecules identified in screens designed with a basic biology perspective. We reflect on the possibilities that lie ahead and discuss some of the potential pitfalls that might be encountered upon adopting a given chemical genetics approach. PMID:28275150

  19. Attitude towards Pre-Marital Genetic Screening among Students of Osun State Polytechnics in Nigeria

    ERIC Educational Resources Information Center

    Odelola, J. O.; Adisa, O.; Akintaro, O. A.

    2013-01-01

    This study investigated the attitude towards pre-marital genetic screening among students of Osun State Polytechnics. Descriptive survey design was used for the study. The instrument for data collection was self developed and structured questionnaire in four-point likert scale format. Descriptive statistics of frequency count and percentages were…

  20. Optimal euploid embryo transfer strategy, fresh versus frozen, after preimplantation genetic screening with next generation sequencing: a randomized controlled trial.

    PubMed

    Coates, Alison; Kung, Allen; Mounts, Emily; Hesla, John; Bankowski, Brandon; Barbieri, Elizabeth; Ata, Baris; Cohen, Jacques; Munné, Santiago

    2017-03-01

    To compare two commonly used protocols (fresh vs. vitrified) used to transfer euploid blastocysts after IVF with preimplantation genetic screening. Randomized controlled trial. Private assisted reproduction center. A total of 179 patients undergoing IVF treatment using preimplantation genetic screening. Patients were randomized at the time of hCG administration to either a freeze-all cycle or a fresh day 6 ET during the stimulated cycle. Implantation rates (sac/embryo transferred), ongoing pregnancy rates (PRs) (beyond 8 weeks), and live birth rate per ET in the primary transfer cycle. Implantation rate per embryo transferred showed an improvement in the frozen group compared with the fresh group, but not significantly (75% vs. 67%). The ongoing PR (80% vs. 61%) and live birth rates (77% vs. 59%) were significantly higher in the frozen group compared with the fresh group. Either treatment protocol investigated in the present study can be a reasonable option for patients. Freezing all embryos allows for inclusion of all blastocysts in the cohort of embryos available for transfer, which also results in a higher proportion of patients reaching ET. These findings suggest a trend toward favoring the freeze-all option as a preferred transfer strategy when using known euploid embryos. NCT02000349. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  1. A novel screening method for influenza patients using a newly developed non-contact screening system.

    PubMed

    Matsui, Takemi; Hakozaki, Yukiya; Suzuki, Satoshi; Usui, Takahiro; Kato, Takehito; Hasegawa, Kousuke; Sugiyama, Youhei; Sugamata, Masami; Abe, Shigeto

    2010-04-01

    In places of mass gathering, rapid infection screening prior to definite diagnosis is vital during the epidemic season of a novel influenza. In order to assess the possibility of clinical application of a newly developed non-contact infection screening system, we conducted screening for influenza patients. The system is operated by a screening program via a linear discriminant analysis using non-contact derived variables, i.e., palmar pulse derived from a laser Doppler blood-flow meter, respiration rate determined by a 10-GHz microwave radar, and average facial temperature measured by thermography. The system was tested on 57 seasonal influenza (2008-2009) patients (35.7 degrees C < or = body temperature < or = 38.3 degrees C, 19-40 years) and 35 normal control subjects (35.5 degrees C < or = body temperature < or = 36.9 degrees C, 21-35 years) at the Japan Self-defense Forces Central Hospital. A significant linear discriminant function (p < 0.001) was determined to distinguish the influenza group from the control group (Mahalanobis D-square = 6.5, classification error rate > 10%). The system had a positive predictive value (PPV) of 93%, which is higher than the PPV value (PPV < or = 65.4%) reported in the recent summary of studies using only thermography performed mainly in hospitals. The proposed system appears promising for application in accurate screening for influenza patients at places of mass gathering. Copyright 2010 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

  2. Tay-Sachs screening: motives for participating and knowledge of genetics and probability.

    PubMed Central

    Childs, B; Gordis, L; Kaback, M M; Kazazian, H H

    1976-01-01

    A highly-educated, socially aware group of persons presented themselves for Tay-Sachs screening having learned about it mainly from friends, newspapers, radio, and television but not from physicians or rabbis. After learning that screening was possible and deciding that it is in principle a good idea, and after discussing it with relatives and friends but not with physicians and rabbis, they presented themselves for the test. Although the participants knew that Tay-Sachs is a serious disease and that Jews are vulnerable, few of them knew much about the genetics of the disease, its frequency, or the incidence of the carrier state. This experience of screening for Tay-Sachs carriers suggests the need for physicians to learn the relation of genetics to preventive medicine, and for the public to learn more about the biology of man. PMID:1008060

  3. Genetic screening of prospective parents and of workers: some scientific and social issues.

    PubMed

    Hubbard, R; Henifin, M S

    1985-01-01

    Genetic screening programs are based on assumptions and values that reflect the history of racial and social eugenics in the United States and Europe. They stigmatize individuals by shifting the focus from social, economic, and political decisions that affect the health of prospective parents, newborns, and workers to "bad genes," that is, intrapersonal factors that are given the status of "causes" of disease. Prenatal screening, at best, can help the relatively few individuals who know that their future children are at risk for a particular inherited disease or disability; it has little positive value for the average person. Workplace genetic screening has not been shown to reduce occupational disease, but it has led to employment discrimination and has drawn attention away from controlling exposures to toxic chemicals in the workplace.

  4. CRISPR-Cas9 for medical genetic screens: applications and future perspectives.

    PubMed

    Xue, Hui-Ying; Ji, Li-Juan; Gao, Ai-Mei; Liu, Ping; He, Jing-Dong; Lu, Xiao-Jie

    2016-02-01

    CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9) systems have emerged as versatile and convenient (epi)genome editing tools and have become an important player in medical genetic research. CRISPR-Cas9 and its variants such as catalytically inactivated Cas9 (dead Cas9, dCas9) and scaffold-incorporating single guide sgRNA (scRNA) have been applied in various genomic screen studies. CRISPR screens enable high-throughput interrogation of gene functions in health and diseases. Compared with conventional RNAi screens, CRISPR screens incur less off-target effects and are more versatile in that they can be used in multiple formats such as knockout, knockdown and activation screens, and can target coding and non-coding regions throughout the genome. This powerful screen platform holds the potential of revolutionising functional genomic studies in the near future. Herein, we introduce the mechanisms of (epi)genome editing mediated by CRISPR-Cas9 and its variants, introduce the procedures and applications of CRISPR screen in functional genomics, compare it with conventional screen tools and at last discuss current challenges and opportunities and propose future directions.

  5. Twenty years of lesson learning: how does the RET genetic screening test impact the clinical management of medullary thyroid cancer?

    PubMed

    Romei, Cristina; Tacito, Alessia; Molinaro, Eleonora; Agate, Laura; Bottici, Valeria; Viola, David; Matrone, Antonio; Biagini, Agnese; Casella, Francesca; Ciampi, Raffaele; Materazzi, Gabriele; Miccoli, Paolo; Torregrossa, Liborio; Ugolini, Clara; Basolo, Fulvio; Vitti, Paolo; Elisei, Rossella

    2015-06-01

    Medullary thyroid carcinoma (MTC) is a rare disease that can be inherited or sporadic; its pathogenesis is related to activating mutations in the RET gene. This study describes our 20-year experience regarding RET genetic screening in MTC. We performed RET genetic screening in 1556 subjects, 1007 with an apparently sporadic MTC, 95 with a familial form and 454 relatives of RET-positive patients with MTC. A germline RET mutation was found in 68 of 1007 (6·7%) patients with sporadic MTC, while 939 patients with MTC were negative for germline RET mutations. We then identified a total of 137 gene carriers (GC). These subjects initiated a clinical evaluation for the diagnosis of MEN 2. A total of 139 MEN 2 families have been followed: 94 FMTC, 33 MEN 2A and 12 MEN 2B. Thirty-three different germline RET mutations were identified. Codon 804 was the most frequently altered codon particularly in FMTC (32/94, 34%), while codon 634 was the most frequently altered codon in MEN 2A (31/33, 94%); MEN 2B cases were exclusively associated with an M918T mutation at exon 16. Our 20-year study demonstrated that RET genetic screening is highly specific and sensitive, and it allows the reclassification as hereditary of apparently sporadic cases and the identification of GC who require an adequate follow-up. We confirmed that FMTC is the most prevalent MEN 2 syndrome and that it is strongly correlated with noncysteine RET mutations. According to these findings, a new paradigm of follow-up of hereditary MTC cases might be considered in the next future. © 2014 John Wiley & Sons Ltd.

  6. [The significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis].

    PubMed

    Zhang, J; Wang, Y N; Wang, J S; Wu, L; Wei, N; Fu, L; Gao, Z; Chen, J H; Pei, R J; Wang, Z

    2016-07-01

    To investigate the significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis (HLH). Four cases of primary HLH patients with PRF1, UNC13D and SH2D1A gene mutations were conducted pedigree investigation, including family genetic screening and detections of immunological parameters (NK cell activity, CD107a degranulation and expression of HLH related defective protein), to evaluate the significance of these different indicators in the diagnosis of primary HLH and explore their correlations. The DNA mutations of the four families included missense mutation c.T172C (p.S58P) and non- frameshift deletions c.1083_1094del (p.361_365del), missense mutation c.C1349T (p.T450M) and frameshift mutation c.1090_1091delCT (p.T364fsX93) in PRF1 gene, missense mutation c.G2588A (p.G863D) in UNC13D gene and hemizygous mutation c.32T>G (p.I11S) in SH2D1A gene. The patients and their family members presented decreased NK cell activities. Individuals who carried mutations of PRF1 gene and SH2D1A gene showed low expression of perforin (PRF1) and signaling lymphocytic activation molecule associated protein (SAP). And the patient with UNC13D gene mutation and his family member with identical mutation showed significant reducing cytotoxic degranulation function (expression of CD107a). Pedigree genetic screening and rapid detection of immunological parameters might play an important role in the diagnosis of primary HLH, and both of them had good consistency. As an efficient detection means, the rapid immunological detection indicators would provide reliable basis for the early diagnosis of the primary HLH.

  7. Preliminary Screening Results of Fabry Disease in Kidney Transplantation Patients: A Single-Center Study.

    PubMed

    Yılmaz, M; Uçar, S K; Aşçı, G; Canda, E; Tan, F A; Hoşcoşkun, C; Çoker, M; Töz, H

    2017-04-01

    Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by the deficiency of alfa-galactosidase A (AGALA) and leads to progressive impairment of renal function in almost all male patients and in a significant proportion of female patients. FD is underdiagnosed or even misdiagnosed in patients undergoing kidney transplantation. We initiated a selective screening study for FD among kidney transplant patients in our center. In this study, 1095 male and female patients were included. Dried blood samples on Guthrie papers were used to analyze galactosidase A enzyme for male patients. Genetic analyses were performed in all female and male patients with low enzyme activity. In total, 648 female and 447 male patients with functioning grafts were evaluated. Among 1095 patients, 5 male patients had AGALA activity below threshold and 3 female patients had galactosidase alpha gene DNA variations. One male patient had a disease-causing mutation. The other 4 patients had polymorphisms causing low enzyme activity. All the 3 female patients had mutations that were associated with FD according to Human Gene Mutation Database (ID: CM025441). In contrast, these mutations were reported as unknown clinical significance in Clinvar (rs149391489). The patients with clinical findings suggesting FD were planned to be analyzed for Lyso Gb3. In our selective screening study, 8 variations were found among 1095 kidney transplantation patients, which needs further investigation to determine causes of FD. Clinical findings, physical examination, and family history are also necessary to evaluate the genetic changes as a mutation in this selected population.

  8. Patient-Reported Barriers to Colorectal Cancer Screening

    PubMed Central

    Jones, Resa M.; Devers, Kelly J.; Kuzel, Anton J.; Woolf, Steven H.

    2010-01-01

    Background Barriers experienced by patients influence the uptake of colorectal cancer (CRC) screening. Prior research has quantified how often patients encounter these challenges but has generally not revealed their complex perspective and experience with barriers. Methods A two-part, mixed-methods study was conducted of primary care patients recruited from Virginia Ambulatory Care Outcome Research Network practices. First, in June–July 2005 a survey was mailed to 660 patients aged 50–75 years posing an open-ended question about “the most important barrier” to CRC screening. Second, beginning in October 2005 seven gender- and largely race-specific focus groups involving 40 patients aged 45–75 years were conducted. Beginning in October 2005, survey verbatim responses were coded and quantitatively analyzed and focus group transcripts were qualitatively analyzed. Results Responses to the open-ended survey question, answered by 74% of respondents, identified fear and the bowel preparation as the most important barriers to screening. Only 1.6% of responses cited the absence of physician advice. Focus group participants cited similar issues and other previously reported barriers, but their remarks exposed the intricacies of complex barriers, such as fear, lack of information, time, the role of physicians, and access to care. Participants also cited barriers that have little documentation in the literature, such as low self-worth, “para-sexual” sensitivities, fatalism, negative past experiences with testing, and skepticism about the financial motivation behind screening recommendations. Conclusions Mixed-methods analysis helps to disaggregate the complex nuances that influence patient behavior. In this study, patients explained the web of influences on knowledge, motivation, and ability to undergo CRC screening, which clinicians and policymakers should consider in designing interventions to increase the level of screening. PMID:20409499

  9. Patients' opinions about suicide screening in a pediatric emergency department.

    PubMed

    Ballard, Elizabeth D; Bosk, Abigail; Snyder, Deborah; Pao, Maryland; Bridge, Jeffrey A; Wharff, Elizabeth A; Teach, Stephen J; Horowitz, Lisa

    2012-01-01

    Understanding how children react to suicide screening in an emergency department (ED) can inform implementation strategies. This qualitative study describes pediatric patients' opinions regarding suicide screening in that setting. As part of a multisite instrument validation study, patients 10 to 21 years presenting with both psychiatric and nonpsychiatric complaints to an urban, tertiary care pediatric ED were recruited for suicide screening. Interviews with subjects included the question, "do you think ER nurses should ask kids about suicide/thoughts about hurting themselves...why/why not?" Responses were transcribed verbatim and uploaded into NVivo8.0 qualitative software for coding and content analysis. Of the 156 patients who participated in the study, 106 (68%) presented to the ED with nonpsychiatric complaints and 50 (32%) presented with psychiatric complaints. The patients' mean (SD) age was 14.6 (2.8) years (range, 10-21 years), and 56% of the sample was female. All patients answered the question of interest, and 149 (96%) of 156 patients supported the idea that nurses should ask youth about suicide in the ED. The 5 most frequently endorsed themes were as follows: (1) identification of youth at risk (31/156, 20%), (2) a desire to feel known and understood by clinicians (31/156, 20%), (3) connection of youth with help and resources (28/156, 18%), (4) prevention of suicidal behavior (25/156, 16%), and (5) lack of other individuals to speak with about these issues (19/156, 12%). Pediatric patients in the ED support suicide screening after being asked a number of suicide-related questions. Further work should evaluate the impact of suicide screening on referral practices and link screening efforts with evidence-based interventions.

  10. Role of Genetic Testing in Patients with Ventricular Arrhythmias in Apparently Normal Hearts.

    PubMed

    Hofman, Nynke; Wilde, Arthur A M

    2016-09-01

    Ventricular arrhythmias without structural heart disease are responsible for ∼35% of patients who have sudden cardiac death before the age of 40 years. Molecular autopsy and/or cardiological investigation of nearby family members often reveals the diagnosis and genetic testing can be helpful in family screening and risk stratification in disease carriers. Extended gene panels can be screened in a short period of time at low cost. A multidisciplinary team of (genetically) specialized clinicians is necessary to judge all the available details and to decide on the significance of the variant and further strategies.

  11. A forward genetic screen identifies erythrocyte CD55 as essential for Plasmodium falciparum invasion **

    PubMed Central

    Egan, Elizabeth S.; Jiang, Rays H.Y.; Moechtar, Mischka A.; Barteneva, Natasha S.; Weekes, Michael P.; Nobre, Luis V.; Gygi, Steven P.; Paulo, Joao A.; Frantzreb, Charles; Tani, Yoshihiko; Takahashi, Junko; Watanabe, Seishi; Goldberg, Jonathan; Paul, Aditya S.; Brugnara, Carlo; Root, David E.; Wiegand, Roger C.; Doench, John G.; Duraisingh, Manoj T.

    2015-01-01

    Efforts to identify host determinants for malaria have been hindered by the absence of a nucleus in erythrocytes, precluding genetic manipulation in the cell where the parasite replicates. We used cultured red blood cells derived from hematopoietic stem cells to carry out a forward genetic screen for Plasmodium falciparum host determinants. We found that CD55 is an essential host factor for P. falciparum invasion. CD55-null erythrocytes were refractory to invasion by all isolates of P. falciparum because parasites failed to attach properly to the erythrocyte surface. Thus, CD55 is an attractive target for the development of malaria therapeutics. Hematopoietic stem cell-based forward genetic screens may be valuable for the identification of additional host determinants of malaria pathogenesis. PMID:25954012

  12. Genetic secrets: social issues of medical screening in a genetic age.

    PubMed

    Draper, Elaine

    1992-01-01

    In the 1990s, as the multi-billion-dollar Human Genome Project makes more and more genetic information available, we would do well to look closely at the social context of power dynamics, control, and economic interests within which that information will be used. Let us consider four specific questions. How does social stratification by race, ethnicity, gender, and social class affect the use of genetic information in the workplace? In what ways are perspectives on genetic testing socially located? What can fetal exclusion policies teach us about how genetic information might be used to identify high-risk individuals? What social and political challenges are posed by new information about genetic abnormalities, and how might that information be distributed fairly?

  13. Patient Perspectives on Intimate Partner Violence Discussion during Genetic Counseling Sessions.

    PubMed

    Chen, Christina; Greb, Anne; Kalia, Isha; Bajaj, Komal; Klugman, Susan

    2017-04-01

    Intimate partner violence (IPV) is a major health concern in the United States (ACOG 2013). The World Health Organization (WHO) describes IPV as any physical, sexual, psychological harm by a current or former intimate partner (WHO 2016). Due to the psychosocial depth and nature of discussions within genetic counseling sessions, patients may disclose and/or discuss IPV as it relates to sexual well-being, reproductive and overall health. This study aims to assess the role for IPV screening, counseling and intervention in genetic counseling practice by investigating the incidence, experiences and attitudes about IPV among genetic counseling patients. Patients receiving genetic counseling at an urban metropolitan hospital were anonymously surveyed about experiences and perspectives on IPV as a topic of discussion during genetic counseling sessions. Among 60 eligible patients, 50 completed the survey (49 females, 1 male, of which, 5 identified as LGBT) ages 20 to 66. The incidence of IPV in this group was 16.0 % (n = 8). Majority of participants had never been asked about IPV by a healthcare provider (n = 32; 64.0%), would have felt comfortable answering questions about IPV by their healthcare provider (n = 34; 68.0%), and would have felt comfortable answering questions about IPV by their genetic counselor (n = 39; 78.0%). Perspectives from all participants, notably those with IPV history, provided insights to the role of genetic counselors in areas for IPV screening and counseling training.

  14. Efficacy of MCAD screening in SIDS patients in Tennessee

    SciTech Connect

    Phillips, J.A. III; Vnencak-Jones, C.L.; Ulm, J.E.

    1994-09-01

    Medium chain acyl-CoA deficiency (MCAD) is an autosomal recessive disorder of fatty acid oxidation. While several mutations have been identified in the MCAD gene, an A to G point mutation affecting codon 329 (K329E) represents >90% of those reported. Unfortunately, the reported carrier frequency of this mutation varies greatly between populations which reduces the efficiency of neonatal screening. Mounting evidence suggests a correlation between MCAD deficiency and sudden infant death syndrome (SIDS). To determine the utility of MCAD screening in SIDS patients, we screened for the K329E mutation in DNA extracted from paraffin blocks retrieved from 75 consecutive SIDS patients. Two of 75 (2.7%) had DNA findings consistent with MCAD. One patient (A) was homozygous for K329E while a second patient (B) was heterozygous for K329E. Although the second abnormal MCAD allele has not yet been identified in this patient, in a clinical setting of SIDS, this patient may well represent a compound heterozygote. Subsequent to the analysis, the family of A was contacted and a newborn sib was found to be homozygous for K329E. Carnitine supplementation and frequent feedings were started and the child is doing well. Evaluation of family B is planned. Our finding of 2/75 SIDS patients with DNA findings suggestive of MCAD demonstrates the efficacy of MCAD screening in this population in contrast to that of newborn screening in TN where the estimated K329E carrier frequency is 1/249 and the calculated incidence of MCAD disease is approximately 1/248,000. Our study (1) confirms the finding of MCAD in 2 to 3% of consecutive SIDS patients, (2) utility of DNA testing in presymtomatic sibs of SIDS patients attributable to MCAD and (3) provides accurate recurrent risks and enables prenatal testing for SIDS families where the diagnosis of MCAD has been established.

  15. Validation of a dysphagia screening tool in acute stroke patients.

    PubMed

    Edmiaston, Jeff; Connor, Lisa Tabor; Loehr, Lynda; Nassief, Abdullah

    2010-07-01

    Although many dysphagia screening tools exist, none has high sensitivity and reliability or can be administered quickly with minimal training. To design and validate a swallowing screening tool to be used by health care professionals who are not speech language pathologists to identify dysphagia and aspiration risk in acute stroke patients. In a prospective study of 300 patients admitted to the stroke service at an urban tertiary care hospital, interrater and test-retest reliabilities of a new tool (the Acute Stroke Dysphagia Screen) were established. The tool was administered by nursing staff when patients were admitted to the stroke unit. A speech language pathologist blinded to the results with the new tool administered the Mann Assessment of Swallowing Ability, a clinical bedside evaluation, with dysphagia operationally defined by a score less than 178. The mean time from admission to screening with the new tool was 8 hours. The mean time between administration of the new tool and the clinical bedside evaluation was 32 hours. For the new tool, interrater reliability was 93.6% and test-retest reliability was 92.5%. The new tool had a sensitivity of 91% and a specificity of 74% for detecting dysphagia and a sensitivity of 95% and a specificity of 68% for detecting aspiration risk. The Acute Stroke Dysphagia Screen is an easily administered and reliable tool that has sufficient sensitivity to detect both dysphagia and aspiration risk in acute stroke patients.

  16. Validation of a Dysphagia Screening Tool in Acute Stroke Patients

    PubMed Central

    Edmiaston, Jeff; Connor, Lisa Tabor; Loehr, Lynda; Nassief, Abdullah

    2010-01-01

    Background Although many dysphagia screening tools exist, none has high sensitivity and reliability or can be administered quickly with minimal training. Objective To design and validate a swallowing screening tool to be used by health care professionals who are not speech language pathologists to identify dysphagia and aspiration risk in acute stroke patients. Methods In a prospective study of 300 patients admitted to the stroke service at an urban tertiary care hospital, interrater and test-retest reliabilities of a new tool (the Acute Stroke Dysphagia Screen) were established. The tool was administered by nursing staff when patients were admitted to the stroke unit. A speech language pathologist blinded to the results with the new tool administered the Mann Assessment of Swallowing Ability, a clinical bedside evaluation, with dysphagia operationally defined by a score less than 178. Results The mean time from admission to screening with the new tool was 8 hours. The mean time between administration of the new tool and the clinical bedside evaluation was 32 hours. For the new tool, interrater reliability was 93.6% and test-retest reliability was 92.5%. The new tool had a sensitivity of 91% and a specificity of 74% for detecting dysphagia and a sensitivity of 95% and a specificity of 68% for detecting aspiration risk. Conclusions The Acute Stroke Dysphagia Screen is an easily administered and reliable tool that has sufficient sensitivity to detect both dysphagia and aspiration risk in acute stroke patients. PMID:19875722

  17. Patient decision-making for clinical genetics.

    PubMed

    Anderson, Gwen

    2007-03-01

    Medicine is incorporating genetic services into all avenues of health-care, ranging from the rarest to the most common diseases. Cognitive theories of decision-making still dominate professionals' understanding of patient decision-making about how to use genetic information and whether to have testing. I discovered a conceptual model of decision-making while carrying out a phenomenological-hermeneutic descriptive study of a convenience sample of 12 couples who were interviewed while deciding whether to undergo prenatal genetic testing. Thirty-two interviews were conducted with 12 men and 12 women separately. Interviews were transcribed verbatim and all data were analyzed using three levels of coding that were sorted into 30 categories and then abstracted into three emergent meta-themes that described men's and women's attempts to make sense and find meaning in how to best use prenatal genetic technology. Their descriptions of how they thought about, communicated, and coped with their decision were so detailed it was possible to discern nine different types of thinking they engaged in while deciding to accept or decline testing. They believed that decision-making is a process of working through your own personal style of thinking. This might include only one or any combination of the following types of thinking: analytical, ethical, moral, reflective, practical, hypothetical, judgmental, scary, and second sight, as described in detail by these 12 couples.

  18. Genetic dissection of Flaviviridae host factors through genome-scale CRISPR screens

    PubMed Central

    Marceau, Caleb D.; Puschnik, Andreas S.; Majzoub, Karim; Ooi, Yaw Shin; Brewer, Susan M.; Fuchs, Gabriele; Swaminathan, Kavya; Mata, Miguel A.; Elias, Joshua E.; Sarnow, Peter; Carette, Jan E.

    2016-01-01

    Summary The Flaviviridae are a family of viruses that cause severe human diseases. For example, dengue virus (DENV) is a rapidly emerging pathogen causing an estimated 100 million symptomatic infections annually worldwide1. No approved antivirals are available to date and clinical trials with a tetravalent dengue vaccine showed disappointingly low protection rates2. Also hepatitis C virus (HCV) remains a major medical problem with 160 million chronically infected patients and only expensive treatment on the market3. Despite distinct differences in pathogenesis and mode of transmission, the two viruses share common replication strategies4. A detailed understanding of the host functions that determine viral infection is lacking. Here, we utilized a pooled CRISPR genetic screening strategy5,6 to comprehensively dissect host factors required for these two highly important Flaviviridae members. For DENV, we identified ER-associated multi-protein complexes involved in signal sequence recognition, N-linked glycosylation and ER associated degradation. Dengue virus replication was nearly completely abrogated in cells deficient in the oligosaccharyltransferase (OST) complex. Mechanistic studies pinpointed viral RNA replication and not entry or translation as critical step requiring the OST complex. Moreover, we showed that viral non-structural proteins bind to the OST complex. The identified ER-associated protein complexes were also important for other mosquito-borne flaviviruses including Zika virus, an emerging pathogen causing severe birth defects7. In contrast, the most significant genes identified in the HCV screen were distinct and included viral receptors, RNA binding proteins and enzymes involved in metabolism. We discovered an unexpected link between intracellular FAD levels and HCV replication. This study shows remarkable divergence in host dependency factors between DENV and HCV and illuminates novel host targets for antiviral therapy. PMID:27383987

  19. The UCSF screening exam effectively screens cognitive and behavioral impairment in patients with ALS.

    PubMed

    Murphy, Jennifer; Ahmed, Fizaa; Lomen-Hoerth, Catherine

    2015-03-01

    The University of California San Francisco (UCSF) Screening Battery provides clinicians with a uniquely tailored tool to measure ALS patients' cognitive and behavioral changes, adjusting for dysarthria and hand weakness. The battery consists of the ALS-CBS ( 1 ), Written Fluency Test ( 2 ), and a new revision of the Frontal Behavior Inventory (FBI-ALS) ( 3 ). The validity of each component was tested by comparing results with a gold standard neuropsychological exam (GNE). Consensus criteria-based GNE diagnoses ( 4 ) were assigned (n = 24) and concurrent validity was tested for each screening exam component. Results showed that each of the four cognitive and behavioral screening test components were significantly associated with diagnoses confirmed by GNE. GNE diagnoses were significantly associated with FBI-ALS negative score, written S-words score, and ALS-CBS cognitive score. The total FBI-ALS score and C-words tests were less predictive of GNE-diagnosed impairment. In conclusion, the UCSF Cognitive Screening Battery demonstrates good external validity compared with GNE in this modest sample, encouraging its use in larger investigations. These data suggest that this battery may provide an effective screen to identify ALS patients who will then benefit from a full examination to confirm their diagnosis.

  20. 140 Genome-wide CRISPR/cas9 Knockout Screens in Human Glioblastoma Identify Genetic Vulnerabilities.

    PubMed

    Noorani, Imran

    2016-08-01

    Glioblastoma is the most common primary brain tumor with a poor prognosis. Identifying the genetic vulnerabilities of cancer is a novel method for discovering new cancer therapeutic targets. The genetic vulnerabilities of glioblastoma are poorly understood, however. The recent CRISPR/cas9 genetic knockout approach has been proposed as a useful method for high-throughput screening of such genetic liabilities. We established human glioblastoma stem cell lines from 5 patients with primary glioblastoma. The validity of these cell lines was confirmed by demonstrating expression of nestin and SOX2 with RT-PCR, and of CD133 with flow cytometry. Cell lines were subcutaneously injected into mice to track tumor growth in vivo. Lentiviral transfection of a cas9 vector followed by antibiotic selection led to generation of stable cas9-expressing cell lines. A genome-wide library containing 123 411 CRISPR guide RNAs (6 guide RNAs per gene, targeting 19 050 genes) was lentivirally transfected into these cell lines. DNA was extracted from cells and sequenced with Illumina Hi-Seq at day 1 and day 25 after transfection. These patient-derived stem cell lines displayed clonal sphere growth of between 42% and 61%, with a median time survival time of 40 days when transplanted into immunocompromised mice. High-throughput sequencing revealed significant depletion of CRISPR guide RNAs for 1190 genes, with a high degree of overlap between independent replicates for a given cell line. Analysis of gene function using ontology databases demonstrated that DNA repair pathways, RNA and protein synthesis, and regulators of cell proliferation were significantly depleted genes. Moreover, a number of genes specific for neuronal proliferation and differentiation were identified. Comparison with known genetic vulnerabilities of other cancer types revealed a specific profile of genetic liabilities unique to glioblastoma. We have identified a unique genetic vulnerability profile for glioblastoma

  1. Accelerating glioblastoma drug discovery: Convergence of patient-derived models, genome editing and phenotypic screening.

    PubMed

    O'Duibhir, Eoghan; Carragher, Neil O; Pollard, Steven M

    2017-04-01

    Patients diagnosed with glioblastoma (GBM) continue to face a bleak prognosis. It is critical that new effective therapeutic strategies are developed. GBM stem cells have molecular hallmarks of neural stem and progenitor cells and it is possible to propagate both non-transformed normal neural stem cells and GBM stem cells, in defined, feeder-free, adherent culture. These primary stem cell lines provide an experimental model that is ideally suited to cell-based drug discovery or genetic screens in order to identify tumour-specific vulnerabilities. For many solid tumours, including GBM, the genetic disruptions that drive tumour initiation and growth have now been catalogued. CRISPR/Cas-based genome editing technologies have recently emerged, transforming our ability to functionally annotate the human genome. Genome editing opens prospects for engineering precise genetic changes in normal and GBM-derived neural stem cells, which will provide more defined and reliable genetic models, with critical matched pairs of isogenic cell lines. Generation of more complex alleles such as knock in tags or fluorescent reporters is also now possible. These new cellular models can be deployed in cell-based phenotypic drug discovery (PDD). Here we discuss the convergence of these advanced technologies (iPS cells, neural stem cell culture, genome editing and high content phenotypic screening) and how they herald a new era in human cellular genetics that should have a major impact in accelerating glioblastoma drug discovery. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Onsite QTc interval screening for patients in methadone maintenance treatment.

    PubMed

    Fareed, Ayman; Vayalapalli, Sreedevi; Byrd-Sellers, Johnita; Casarella, Jennifer; Drexler, Karen; Amar, Richard; Smith-Cox, Jocelyn; Lutchman, Tamara Shaw

    2010-01-01

    To improve the electrocardiogram screening process and early detection of patients at high risk for cardiac arrhythmias, the authors created a model in their clinic where they provided an onsite electrocardiogram screening that might be feasible and practical. The authors then performed a retrospective chart review to access the efficacy and feasibility of their new onsite procedure in identifying methadone maintained patients at high risk for cardiac arrhythmias. Records from all patients who are currently or had previously been maintained on methadone in the methadone maintenance program at the Atlanta VA Medical Center between 2002 and 2009 were evaluated. Of the 140 patients treated at the clinic between 2002 and 2009, 85 were excluded from the study because they had been treated as guests (had been in treatment in other clinics but received methadone dosing temporarily from our clinic), were treated in the clinic for less than 6 months, or dropped out of treatment. Thus, 55 patient charts were selected for review. Most patients (95%) received baseline and annual electrocardiogram screening. The average baseline QTc was (417 +/- 30) and most recent QTc (442 +/- 25). This QTc prolongation from baseline showed statistical significance (P < .0001). Sixty-seven percent of patients had statistically significant QTc prolongation from baseline but was less than 450 ms (mean: 428 +/- 16, P = .008). Twenty-seven percent of patients had statistically significant QTc prolongation from baseline of more 450 ms but was less than 500 ms (mean: 460 +/- 8, P < .0001). Six percent of patients had statistically significant QTc prolongation from baseline of more 500 ms (mean: 503 +/- 1.15, P = .027). Recent cocaine use was the only individual variable that showed statistically significant correlation with QTc prolongation (F = 6.98, P = .01). The authors demonstrated in this study that providing an onsite electrocardiogram screening with a focus on patient education and limiting

  3. Delirium Screening: A Systematic Review of Delirium Screening Tools in Hospitalized Patients.

    PubMed

    De, Jayita; Wand, Anne P F

    2015-12-01

    Delirium occurs commonly in hospitalized older patients but is poorly recognized. Although there are a plethora of validated delirium screening tools, it is unclear which tool best suits particular populations. To evaluate validation studies of delirium screening tools in non-critically ill hospital inpatients and provide guidance on the choice of screening tool. The MEDLINE, CINAHL, and PsychInfo databases were searched for studies comparing delirium bedside screening tools with either the Diagnostic and Statistical Manual or International Classification of Diseases defined diagnosis of delirium in hospital inpatients. Information was also drawn from conference proceedings and discussion with delirium researchers. Thirty-one studies describing 21 delirium screening tools were included in the systematic review. The majority of studies were conducted across a broad range of inpatient settings internationally in elderly inpatients, including patients with dementia but most excluded nonnative language speakers. The Confusion Assessment Method was the most widely used instrument to identify delirium, however, specific training is required to ensure optimum performance. The Delirium Rating Scale and its revised version performed best in the psychogeriatric population but requires an operator with psychiatric training. The Nurses' Delirium Screening Checklist appears best suited to the surgical and recovery room setting. The Single Question in Delirium shows promise in oncology patients. The Memorial Delirium Assessment Scale, while demonstrating good measures of validity in the surgical and palliative care setting, may be better used a measure of delirium severity. The 4As Test performed well when delirium was superimposed on dementia, but it requires further study. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing

    PubMed Central

    Domingo, E; Laiho, P; Ollikainen, M; Pinto, M; Wang, L; French, A; Westra, J; Frebourg, T; Espin, E; Armengol, M; Hamelin, R; Yamamoto, H; Hofstra, R; Seruca, R; Lindblom, A; Peltomaki, P; Thibodeau, S; Aaltonen, L; Schwartz, S

    2004-01-01

    Background: According to the international criteria for hereditary non-polyposis colorectal cancer (HNPCC) diagnostics, cancer patients with a family history or early onset of colorectal tumours showing high microsatellite instability (MSI-H) should receive genetic counselling and be offered testing for germline mutations in DNA repair genes, mainly MLH1 and MSH2. Recently, an oncogenic V600E hotspot mutation within BRAF, a kinase encoding gene from the RAS/RAF/MAPK pathway, has been found to be associated with sporadic MSI-H colon cancer, but its association with HNPCC remains to be further clarified. Methods: BRAF-V600E mutations were analysed by automatic sequencing in colorectal cancers from 206 sporadic cases with MSI-H and 111 HNPCC cases with known germline mutations in MLH1 and MSH2. In addition, 45 HNPCC cases showing abnormal immunostaining for MSH2 were also analysed. Results: The BRAF-V600E hotspot mutation was found in 40% (82/206) of the sporadic MSI-H tumours analysed but in none of the 111 tested HNPCC tumours or in the 45 cases showing abnormal MSH2 immunostaining. Conclusions: Detection of the V600E mutation in a colorectal MSI-H tumour argues against the presence of a germline mutation in either the MLH1 or MSH2 gene. Therefore, screening of these mismatch repair (MMR) genes can be avoided in cases positive for V600E if no other significant evidence, such as fulfilment of the strict Amsterdam criteria, suggests MMR associated HNPCC. In this context, mutation analysis of the BRAF hotspot is a reliable, fast, and low cost strategy which simplifies genetic testing for HNPCC. PMID:15342696

  5. BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing.

    PubMed

    Domingo, E; Laiho, P; Ollikainen, M; Pinto, M; Wang, L; French, A J; Westra, J; Frebourg, T; Espín, E; Armengol, M; Hamelin, R; Yamamoto, H; Hofstra, R M W; Seruca, R; Lindblom, A; Peltomäki, P; Thibodeau, S N; Aaltonen, L A; Schwartz, S

    2004-09-01

    According to the international criteria for hereditary non-polyposis colorectal cancer (HNPCC) diagnostics, cancer patients with a family history or early onset of colorectal tumours showing high microsatellite instability (MSI-H) should receive genetic counselling and be offered testing for germline mutations in DNA repair genes, mainly MLH1 and MSH2. Recently, an oncogenic V600E hotspot mutation within BRAF, a kinase encoding gene from the RAS/RAF/MAPK pathway, has been found to be associated with sporadic MSI-H colon cancer, but its association with HNPCC remains to be further clarified. BRAF-V600E mutations were analysed by automatic sequencing in colorectal cancers from 206 sporadic cases with MSI-H and 111 HNPCC cases with known germline mutations in MLH1 and MSH2. In addition, 45 HNPCC cases showing abnormal immunostaining for MSH2 were also analysed. The BRAF-V600E hotspot mutation was found in 40% (82/206) of the sporadic MSI-H tumours analysed but in none of the 111 tested HNPCC tumours or in the 45 cases showing abnormal MSH2 immunostaining. Detection of the V600E mutation in a colorectal MSI-H tumour argues against the presence of a germline mutation in either the MLH1 or MSH2 gene. Therefore, screening of these mismatch repair (MMR) genes can be avoided in cases positive for V600E if no other significant evidence, such as fulfilment of the strict Amsterdam criteria, suggests MMR associated HNPCC. In this context, mutation analysis of the BRAF hotspot is a reliable, fast, and low cost strategy which simplifies genetic testing for HNPCC.

  6. Dipstick urinalysis for diabetes screening in TB patients

    PubMed Central

    Restrepo, Blanca I.; Pino, Paula A.; Zarate, Izelda; Mora-Guzman, Francisco

    2013-01-01

    Introduction Diabetes knowledge among TB patients can contribute to improved TB treatment outcomes, but lack of diabetes diagnosis awareness is a limitation in developing countries. Given its low cost, the sensitivity of urine glucose dipsticks for diabetes screening in TB patients was assessed. Methods Glycosuria was assessed in 90 newly diagnosed TB patients (38 with diabetes) in south Texas, USA (n = 20) and northeast Mexico (n = 70) during January 2009–December 2010. Results Glycosuria was detected in 65% of the diabetic patients with chronic hyperglycemia (positive predictive value 91%, negative predictive value 84%). Conclusion We propose that TB clinics with limited budgets where portable glucometers may not be available conduct universal screening for diabetes with urine dipsticks. This could be followed by blood glucose or HbA1c testing in the subset of patients requiring confirmation or higher sensitivity assessment, to improve the comanagement of TB and diabetes. PMID:24030116

  7. Screening Cardiac Surgery Patients for MRSA: An Economic Computer Model

    PubMed Central

    Lee, Bruce Y.; Wiringa, Ann E.; Bailey, Rachel R.; Goyal, Vishal; Lewis, G. Jonathan; Tsui, Becky Y. K.; Smith, Kenneth J.; Muder, Robert R.

    2012-01-01

    Objective To estimate the economic value of preoperative methicillin-resistant Staphylococcus aureus (MRSA) screening and decolonization for cardiac surgery patients. Study Design Monte Carlo decision-analytic computer simulation model. Methods We developed a computer simulation model representing the decision of whether to perform preoperative MRSA screening and decolonizing those patients with a positive MRSA culture. Sensitivity analyses varied key input parameters including MRSA colonization prevalence, decolonization success rates, the number of surveillance sites, and screening/decolonization costs. Separate analyses estimated the incremental cost-effectiveness ratio (ICER) of the screening and decolonization strategy from the third-party payer and hospital perspectives. Results Even when MRSA colonization prevalence and decolonization success rate were as low as 1% and 25%, respectively, the ICER of implementing routine surveillance was well under $15,000 per quality-adjusted life-year from both the third-party payer and hospital perspectives. The surveillance strategy was economically dominant (less costly and more effective than no testing) for most scenarios explored. Conclusions Our results suggest that routine preoperative MRSA screening of cardiac surgery patients could provide substantial economic value to third-party payers and hospitals over a wide range of MRSA colonization prevalence levels, decolonization success rates, and surveillance costs. Healthcare administrators, infection control specialists, and surgeons can compare their local conditions with our study’s benchmarks to make decisions about whether to implement preoperative MRSA testing. Third-party payers may want to consider covering such a strategy. PMID:20645662

  8. [SCREENING OF PRIMARY HYPERPARATHYROIDISM IN PATIENTS WITH UROLITHIASIS].

    PubMed

    Rogozin, D S; Sergiyko, S V; Rogozina, A A

    2015-01-01

    The aim of research was to study the rate of hypercalcemia and primary hyperparathyroidism among patients with uroli- thiasis. The investigation included 645 patients with urolithiasis. Patients were divided into 2 groups: with normocalcemia and hypercalcemia. The rate of hypercalcemia consisted of 18,9% among patients with urolithiasis. This frequency was 10-20 times higher than in a similar rate of general population. There were no significant differences in age, sex, history of urolithiasis and stone localization between two groups. The data obtained showed an importance of screening of hypercalcemia in patients with urolithiasis regardless the severity of clinical course.

  9. Successful birth of South India's first twins after preimplantation genetic screening of embryos

    PubMed Central

    Selvaraj, Priya; Selvaraj, Kamala; Srinivasan, Kalaichelvi; Sivakumar, Mahalakshmi

    2016-01-01

    We report the first documented successful birth of twins following preimplantation genetic screening (PGS) of cleavage stage embryos by array comparative genomic hybridization (CGH) technology, in South India. The case was a 28-year-old woman with the previous history of preclinical pregnancy and a miscarriage in two attempted in vitro fertilization cycles. Day 3 cleavage stage embryos were generated by conventional long protocol with the use of a gonadotropin-releasing hormone analog and a combination of recombinant folliculotropins and human menopausal gonadotropins. Intracytoplasmic sperm injection of oocytes thus obtained was performed, and 10 selected embryos underwent PGS using the array CGH technique. Two normal blastocysts were transferred to the patient, and she conceived twins. She delivered at 35 weeks of gestation by elective cesarean on November 19, 2014. She delivered a healthy male and female baby weighing 2.19 kg and 2.26 kg, respectively. Postnatal evaluation of babies was also normal, and the hospital course was uneventful. PGS has a definitive indication in assisted reproductive technology programs and can be utilized to improve pregnancy rates significantly. PMID:27382239

  10. A Post-Developmental Genetic Screen for Zebrafish Models of Inherited Liver Disease

    PubMed Central

    Kim, Seok-Hyung; Wu, Shu-Yu; Baek, Jeong-In; Choi, Soo Young; Su, Yanhui; Flynn, Charles R.; Gamse, Joshua T.; Ess, Kevin C.; Hardiman, Gary; Lipschutz, Joshua H.; Abumrad, Naji N.; Rockey, Don C.

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease such as simple steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis and fibrosis. However, the molecular pathogenesis and genetic variations causing NAFLD are poorly understood. The high prevalence and incidence of NAFLD suggests that genetic variations on a large number of genes might be involved in NAFLD. To identify genetic variants causing inherited liver disease, we used zebrafish as a model system for a large-scale mutant screen, and adopted a whole genome sequencing approach for rapid identification of mutated genes found in our screen. Here, we report on a forward genetic screen of ENU mutagenized zebrafish. From 250 F2 lines of ENU mutagenized zebrafish during post-developmental stages (5 to 8 days post fertilization), we identified 19 unique mutant zebrafish lines displaying visual evidence of hepatomegaly and/or steatosis with no developmental defects. Histological analysis of mutants revealed several specific phenotypes, including common steatosis, micro/macrovesicular steatosis, hepatomegaly, ballooning, and acute hepatocellular necrosis. This work has identified multiple post-developmental mutants and establishes zebrafish as a novel animal model for post-developmental inherited liver disease. PMID:25950913

  11. A post-developmental genetic screen for zebrafish models of inherited liver disease.

    PubMed

    Kim, Seok-Hyung; Wu, Shu-Yu; Baek, Jeong-In; Choi, Soo Young; Su, Yanhui; Flynn, Charles R; Gamse, Joshua T; Ess, Kevin C; Hardiman, Gary; Lipschutz, Joshua H; Abumrad, Naji N; Rockey, Don C

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease such as simple steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis and fibrosis. However, the molecular pathogenesis and genetic variations causing NAFLD are poorly understood. The high prevalence and incidence of NAFLD suggests that genetic variations on a large number of genes might be involved in NAFLD. To identify genetic variants causing inherited liver disease, we used zebrafish as a model system for a large-scale mutant screen, and adopted a whole genome sequencing approach for rapid identification of mutated genes found in our screen. Here, we report on a forward genetic screen of ENU mutagenized zebrafish. From 250 F2 lines of ENU mutagenized zebrafish during post-developmental stages (5 to 8 days post fertilization), we identified 19 unique mutant zebrafish lines displaying visual evidence of hepatomegaly and/or steatosis with no developmental defects. Histological analysis of mutants revealed several specific phenotypes, including common steatosis, micro/macrovesicular steatosis, hepatomegaly, ballooning, and acute hepatocellular necrosis. This work has identified multiple post-developmental mutants and establishes zebrafish as a novel animal model for post-developmental inherited liver disease.

  12. Postmortem genetic screening for the identification, verification, and reporting of genetic variants contributing to the sudden death of the young.

    PubMed

    Methner, D Nicole R; Scherer, Steven E; Welch, Katherine; Walkiewicz, Magdalena; Eng, Christine M; Belmont, John W; Powell, Mark C; Korchina, Viktoriya; Doddapaneni, Harsha Vardhan; Muzny, Donna M; Gibbs, Richard A; Wolf, Dwayne A; Sanchez, Luis A; Kahn, Roger

    2016-09-01

    Each year in the United States, thousands of cases of sudden and unexpected deaths of infants, children, and young adults are assigned an undetermined cause of death after postmortem investigation and autopsy. Heritable genetic variants have been suggested as the cause of up to a third of sudden death (SD) cases. Elucidation of the genetic variants involved in SD cases is important to not only help establish cause and manner of death of these individuals, but to also aid in determining whether familial genetic testing should be considered. Previously, these types of postmortem screenings have not been a feasible option for most county medical examiners' and coroners' offices. We sequenced full exons of 64 genes associated with SD in the largest known cohort (351) of infant and young SD decedents using massively parallel sequencing at <$600 per sample. Genetic variants were assessed through literature review and clinical evaluation by a multidisciplinary consortium of experts. Thirteen individuals (3.7%), eight infants (2.8% of those <1 yr of age) and five children/young adults (7.0% of those >1 yr of age), were found to have a reportable genetic variant contributing to SD. These percentages represent an estimate lower than those previously reported. Overall yields and results likely vary between studies due to differences in evaluation techniques and reporting. Additionally, we recommend ongoing assessment of data, including nonreported novel variants, as technology and literature continually advance. This study demonstrates a strategy to implement molecular autopsies in medicolegal investigations of young SD decedents.

  13. Genetics of cardiac disease in the small animal patient.

    PubMed

    Meurs, Kathryn M

    2010-07-01

    There is increasing evidence that many forms of congenital and acquired cardiovascular disease in small animal patients are of familial origin. The large number of familial diseases in domestic purebred animals is thought to be associated with the desire to breed related animals to maintain a specific appearance and the selection of animals from a small group of popular founders (founder effect). Clinicians can use knowledge that a particular trait or disease may be inherited to provide guidance to owners and animal breeders to reduce the frequency of the trait. Even if the molecular cause is not known, identification of a pattern of inheritance and information on clinical screening can be useful for a breeder trying to make breeding decisions. Common forms of inheritance for veterinary diseases include autosomal recessive, autosomal dominant, X-linked recessive, and polygenic. These genetic traits and their possible involvement in cardiac disease in small animals are discussed in this article.

  14. Newborn Genetic Screening for Hearing Impairment: A Preliminary Study at a Tertiary Center

    PubMed Central

    Wu, Chen-Chi; Hung, Chia-Cheng; Lin, Shin-Yu; Hsieh, Wu-Shiun; Tsao, Po-Nien; Lee, Chien-Nan; Su, Yi-Ning; Hsu, Chuan-Jen

    2011-01-01

    Universal newborn hearing screening (UNHS) is of paramount importance for early identification and management of hearing impairment in children. However, infants with slight/mild, progressive, or late-onset hearing impairment might be missed in conventional UNHS. To investigate whether genetic screening for common deafness-associated mutations could assist in identifying these infants, 1017 consecutive newborns in a tertiary hospital were subjected to both newborn hearing screening using a two-step distortion-product otoacoustic emissions (DPOAE) screening and newborn genetic screening (NGS) for deafness. The NGS targeted 4 deafness-associated mutations commonly found in the Taiwanese population, including p.V37I (c.109G>A) and c.235delC of the GJB2 gene, c.919-2A>G of the SLC26A4 gene, and mitochondrial m.1555A>G of the 12S rRNA gene. The results of the NGS were then correlated to the results of the NHS. Of the 1017 newborns, 16 (1.6%) had unilateral DPOAE screening failure, and 22 (2.2%) had bilateral DPOAE screening failure. A total of 199 (19.6%) babies were found to have at least 1 mutated allele on the NGS for deafness, 11 (1.1%) of whom were homozygous for GJB2 p.V37I, 6 (0.6%) compound heterozygous for GJB2 p.V37I and c.235delC, and 1 (0.1%) homoplasmic for m.1555A>G, who may potentially have hearing loss. Among them, 3 babies, 5 babies, and 1 baby, respectively, passed the NHS at birth. Comprehensive audiological assessments in the 9 babies at 3 months identified 1 with slight hearing loss and 2 with mild hearing loss. NGS for common deafness-associated mutations may identify infants with slight/mild or potentially progressive hearing impairment, thus compensating for the inherent limitations of the conventional UNHS. PMID:21811586

  15. Screening for abdominal aortic aneurysms in cardiovascular patients.

    PubMed

    Hanly, Ann M; Javad, Shazia; Anderson, Louise P; Horgan, John; Kelly, Cathal J

    2006-05-01

    The objective of the study was to determine the incidence of Abdominal Aortic Aneurysms (AAA) in a population of symptomatic cardiac patients. A retrospective cohort study of investigations was done at the cardiology clinic, Beaumont Hospital, Dublin. There were 415 men and women recruited by referral to the cardiology clinic. All participants underwent routine ultrasound screening for AAA, and full assessment of all cardiac risk factors. Data were analyzed and correlated with age, sex, and diagnosis. Ultrasonographic diagnosis of aneurysm was based on an anteroposterior diameter of 3 cm or more. Of the 415 patients screened, 47 aneurysms were detected. Total incidence of AAA was 9.9% (male 14.1%, female 3.95%). All aneurysms were detected in patients over 60 years, detection rate 11.7% (male 16.3%, female 3.9%). The incidence of AAA was significantly higher in those who were subsequently proven to have cardiovascular disease, 13.8% (male 18%, female 5.15%). Screening the general population for those at risk of AAA is an ongoing debate. This study supports the concept of screening a higher risk population of patients over 60 years with cardiovascular disease.

  16. Screening for coagulation disorders in patients with ischemic stroke.

    PubMed

    de Lau, Lonneke Ml; Leebeek, Frank Wg; de Maat, Moniek Pm; Koudstaal, Peter J; Dippel, Diederik Wj

    2010-08-01

    The role of coagulation disorders in the pathogenesis of (recurrent) ischemic stroke is uncertain. Therefore, the clinical utility of screening patients with ischemic stroke for these conditions and the therapeutic implications of a detected coagulation disorder in a patient who experienced ischemic stroke are uncertain. We reviewed the currently available data on the relationship between various inherited and acquired coagulation abnormalities (factor V Leiden and prothrombin G20210A mutations, deficiencies of protein C, protein S and anti-thrombin, hyperhomocysteinemia, the antiphospholipid syndrome and increased levels of fibrinogen) and ischemic stroke. Based on the existing evidence we discuss the usefulness of screening stroke patients for prothrombotic conditions and current recommendations regarding the optimal management of ischemic stroke patients in whom a coagulation disorder is found.

  17. [Knowledge and willingness of breast cancer patients from Shanghai for genetic counseling and gene testing].

    PubMed

    Cheng, Xiaolin; Li, Zhengdong; Sun, Xiaoyin; Jiang, Beiqi; Zhuang, Zhigang

    2016-10-01

    To investigate the knowledge and willingness of breast cancers patients from Shanghai for genetic counseling and gene testing. A total of 428 patients filled out the questionnaire and the data was statistically analyzed. Most of the patients were unaware of genetic counseling and gene testing. But after a brief introduction, a majority of them were willing to accept genetic counseling and recommend their family members to participate. The willingness was education- and age-related. When told that gene testing may benefit themselves, 92.1% of the patients were willing to be tested. However, when told that gene testing may only benefit their family, only 33.9% of the patients were willing to join the testing. The acceptance was also age-, education- and family income-related. The difference was statistically significant. Moreover, the willingness ratio to participate the gene testing was lower than expected. Overall, 74.1% of the patients were willing to accept cheaper preliminary gene screening, whilst only 19.2% were willing to accept genetic testing of higher price. Despite of being told that testing results will be maintained as confidential, still 43.2% worried about adverse effects. Such patients tended to younger, from low-income families, with a family history of associated cancers, or personal history of other cancers. The difference was statistically significant. The majorities of patients do not know but are willing to accept genetic counseling and gene testing and recommend their family to participate. Lack of genetic knowledge, cost for the testing and concerns about discrimination are the obstacles for patients to participate in genetic counseling and gene testing. To spread the knowledge about breast cancer and establish a follow-up screening system for high-risk population may improve the tertiary prevention for breast cancer.

  18. SCREENING COMMUNITY PHARMACY PATIENTS FOR RISK OF PRESCRIPTION OPIOID MISUSE

    PubMed Central

    Rubinstein, Jessica; Bacci, Jennifer L.; Ylioja, Thomas; Tarter, Ralph

    2016-01-01

    Objectives The current study tested screening feasibility and described the behavioral, mental, and physical health of patients filling prescriptions for opioid medications in the community pharmacy setting. Methods We conducted a cross-sectional survey in rural/urban community pharmacies with adult non-cancer patients. The survey included validated measures for opioid medication misuse risk, drug and alcohol use, and physical and mental health problems. Descriptive statistics were calculated, and bivariate and multivariable logistic regression evaluated relationships between opioid medication misuse risk and patient demographics, behavioral, mental, and physical health. Results 164 patients completed the survey (87% response rate) revealing positive screens for prescription opioid misuse risk (14.3%), illicit drug use (7.3%), hazardous alcohol use (21.4%), depression (25.8%), and post-traumatic stress disorder (PTSD; 17.1%). Bivariate analyses revealed increased odds of a positive opioid medication misuse risk score with a positive screen for illicit drug use in the previous year (OR=3.91, 95% CI=1.05–14.63) and PTSD (OR=6.7, 95% CI= 2.54–17.69). In adjusted multivariable analyses, these relationships strengthened such that a positive screen for illicit drug use (AOR=12.96, 95% CI= 2.18–76.9) and PTSD (AOR=13.3, 95% CI= 3.48–50.66) increased odds for a positive opioid medication misuse risk score. Conclusion Findings confirmed the feasibility of screening risk factors and positive opioid medication misuse risk among community pharmacy patients. Future research should validate these findings as a foundation to intervention development. PMID:26291546

  19. Family Physicians’ Barriers to Cancer Screening in Extremely Obese Patients

    PubMed Central

    Ferrante, Jeanne M.; Fyffe, Denise C.; Vega, Marielos L.; Piasecki, Alicja K.; Ohman-Strickland, Pamela A.; Crabtree, Benjamin F.

    2010-01-01

    Extremely obese women are less likely than nonobese women to receive breast and cervical cancer screening examinations. Reasons for this disparity are unclear and may stem from patient and/or physician barriers. This sequential mixed-methods study used individual in-depth interviews of 15 family physicians followed by a mail survey of 255 family physicians (53% response rate) to understand the barriers they faced in performing cancer screening examinations in extremely obese women. Barriers fell into three main areas: (i) difficulty doing pelvic and breast exams; (ii) inadequate equipment; and (iii) challenges overcoming patient barriers and refusal. This led some physicians to avoid performing breast and pelvic examinations on extremely obese women. Having more knowledge about specific examination techniques was associated with less difficulty in palpating lumps on breast and pelvic examinations (P < 0.005). Physicians perceived that embarrassment, aversion to undressing, and avoidance of discussions related to their weight were the most frequent barriers extremely obese women had with getting physical examinations. Educating and/or motivating patients and addressing fears were strategies used most frequently when patients refused mammograms or Pap smears. Interventions focusing on physician barriers, such as educating them on specific examination techniques, obtaining adequate equipment and supplies, and providing resources to assist physicians in dealing with patient barriers and refusal, may be fruitful in increasing cancer screening rates in extremely obese patients. Future research studies testing the effectiveness of these strategies are needed to improve cancer outcomes in this high-risk population. PMID:20019676

  20. Family physicians' barriers to cancer screening in extremely obese patients.

    PubMed

    Ferrante, Jeanne M; Fyffe, Denise C; Vega, Marielos L; Piasecki, Alicja K; Ohman-Strickland, Pamela A; Crabtree, Benjamin F

    2010-06-01

    Extremely obese women are less likely than nonobese women to receive breast and cervical cancer screening examinations. Reasons for this disparity are unclear and may stem from patient and/or physician barriers. This sequential mixed-methods study used individual in-depth interviews of 15 family physicians followed by a mail survey of 255 family physicians (53% response rate) to understand the barriers they faced in performing cancer screening examinations in extremely obese women. Barriers fell into three main areas: (i) difficulty doing pelvic and breast exams; (ii) inadequate equipment; and (iii) challenges overcoming patient barriers and refusal. This led some physicians to avoid performing breast and pelvic examinations on extremely obese women. Having more knowledge about specific examination techniques was associated with less difficulty in palpating lumps on breast and pelvic examinations (P < 0.005). Physicians perceived that embarrassment, aversion to undressing, and avoidance of discussions related to their weight were the most frequent barriers extremely obese women had with getting physical examinations. Educating and/or motivating patients and addressing fears were strategies used most frequently when patients refused mammograms or Pap smears. Interventions focusing on physician barriers, such as educating them on specific examination techniques, obtaining adequate equipment and supplies, and providing resources to assist physicians in dealing with patient barriers and refusal, may be fruitful in increasing cancer screening rates in extremely obese patients. Future research studies testing the effectiveness of these strategies are needed to improve cancer outcomes in this high-risk population.

  1. From what should we protect future generations: germ-line therapy or genetic screening?

    PubMed

    Mallia, Pierre; ten Have, Henk

    2003-01-01

    This paper discusses the issue of whether we have responsibilities to future generations with respect to genetic screening, including for purposes of selective abortion or discard. Future generations have been discussed at length among scholars. The concept of 'Guardian for Future Generations' is tackled and its main criticisms discussed. Whilst germ-line cures, it is argued, can only affect family trees, genetic screening and testing can have wider implications. If asking how this may affect future generations is a legitimate question and since we indeed make retrospective moral judgements, it would be wise to consider that future generations will make the same retrospective judgements on us. Moreover such technologies affect present embryos to which we indeed can be considered to have an obligation.

  2. Perceptions of colorectal cancer screening in urban African American clinic patients: differences by gender and screening status.

    PubMed

    Bass, Sarah Bauerle; Gordon, Thomas F; Ruzek, Sheryl Burt; Wolak, Caitlin; Ward, Stephanie; Paranjape, Anuradha; Lin, Karen; Meyer, Brian; Ruggieri, Dominique G

    2011-03-01

    African Americans have higher colorectal cancer (CRC) morbidity and mortality than whites, yet have low rates of CRC screening. Few studies have explored African Americans' own perceptions of barriers to CRC screening or elucidated gender differences in screening status. Focus groups were conducted with 23 African American patients between 50 and 70 years of age who were patients in a general internal medicine clinic in a large urban teaching hospital. Focus groups were delimited by gender and CRC screening status. Focus group transcripts were analyzed using an iterative coding process with consensus and triangulation to develop thematic categories. Results indicated key thematic differences in perceptions of screening by gender and CRC screening status. While both men and women who had never been screened had a general lack of knowledge about CRC and screening modalities, women had an overall sense that health screenings were needed and indicated a stronger need to have a positive relationship with their doctor. Women also reported that African American men do not get colonoscopy because of the perceived sexual connotation. Men who had never been screened, compared to those who had been screened, had less trust of their doctors and the health care system and indicated an overall fear of going to the doctor. They also reiterated the sexual connotation of having a colonoscopy and were apprehensive about being sedated during the procedure. Overall, men expressed more fear and were more reluctant to undergo CRC screening than women, but among those who had undergone CRC screening, particularly colonoscopy, men expressed advantages of having the screening. All groups were also found to have a negative attitude about the use of fecal occult blood testing and felt colonoscopy was the superior screening modality. Results suggest that messages and education about CRC screening, particularly colonoscopy, might place more emphasis on accuracy and might be more effective in

  3. Perceptions of Colorectal Cancer Screening in Urban African American Clinic Patients: Differences by Gender and Screening Status

    PubMed Central

    Gordon, Thomas F.; Ruzek, Sheryl Burt; Wolak, Caitlin; Ward, Stephanie; Paranjape, Anuradha; Lin, Karen; Meyer, Brian; Ruggieri, Dominique G.

    2010-01-01

    African Americans have higher colorectal cancer (CRC) morbidity and mortality than whites, yet have low rates of CRC screening. Few studies have explored African Americans’ own perceptions of barriers to CRC screening or elucidated gender differences in screening status. Focus groups were conducted with 23 African American patients between 50 and 70 years of age who were patients in a general internal medicine clinic in a large urban teaching hospital. Focus groups were delimited by gender and CRC screening status. Focus group transcripts were analyzed using an iterative coding process with consensus and triangulation to develop thematic categories. Results indicated key thematic differences in perceptions of screening by gender and CRC screening status. While both men and women who had never been screened had a general lack of knowledge about CRC and screening modalities, women had an overall sense that health screenings were needed and indicated a stronger need to have a positive relationship with their doctor. Women also reported that African American men do not get colonoscopy because of the perceived sexual connotation. Men who had never been screened, compared to those who had been screened, had less trust of their doctors and the health care system and indicated an overall fear of going to the doctor. They also reiterated the sexual connotation of having a colonoscopy and were apprehensive about being sedated during the procedure. Overall, men expressed more fear and were more reluctant to undergo CRC screening than women, but among those who had undergone CRC screening, particularly colonoscopy, men expressed advantages of having the screening. All groups were also found to have a negative attitude about the use of fecal occult blood testing and felt colonoscopy was the superior screening modality. Results suggest that messages and education about CRC screening, particularly colonoscopy, might place more emphasis on accuracy and might be more effective in

  4. A stepwise strategy for rapid and cost-effective RB1 screening in Indian retinoblastoma patients.

    PubMed

    Thirumalairaj, Kannan; Abraham, Aloysius; Devarajan, Bharanidharan; Gaikwad, Namrata; Kim, Usha; Muthukkaruppan, Veerappan; Vanniarajan, Ayyasamy

    2015-09-01

    India has the highest number of retinoblastoma (RB) patients among the developing countries owing to its increasing population. Of the patients with RB, about 40% have the heritable form of the disease, making genetic analysis of the RB1 gene an integral part of disease management. However, given the large size of the RB1 gene with its widely dispersed exons and no reported hotspots, genetic testing can be cumbersome. To overcome this problem, we have developed a rapid screening strategy by prioritizing the order of exons to be analyzed, based on the frequency of nonsense mutations, deletions and duplications reported in the RB1-Leiden Open Variation Database and published literature on Indian patients. Using this strategy for genetic analysis, mutations were identified in 76% of patients in half the actual time and one third of the cost. This reduction in time and cost will allow for better risk prediction for siblings and offspring, thereby facilitating genetic counseling for families, especially in developing countries.

  5. A Simultaneous Genetic Screen for Zygotic and Sterile Mutants in a Hermaphroditic Vertebrate (Kryptolebias marmoratus)

    PubMed Central

    Sucar, Sofia; Moore, Ginger L.; Ard, Melissa E.; Ring, Brian C.

    2016-01-01

    The mangrove killifish, Kryptolebias marmoratus, is unique among vertebrates due to its self-fertilizing mode of reproduction involving an ovotestis. As a result, it constitutes a simplistic and desirable vertebrate model for developmental genetics as it is easily maintained, reaches sexual maturity in about 100 days, and provides a manageable number of relatively clear embryos. After the establishment and characterization of an initial mutagenesis pilot screen using N-ethyl-N-nitrosourea, a three-generation genetic screen was performed to confirm zygotic mutant allele heritability and simultaneously score for homozygous recessive mutant sterile F2 fish. From a total of 307 F2 fish screened, 10 were found to be 1° males, 16 were sterile, 92 wild-type, and the remaining 189, carriers of zygotic recessive alleles. These carriers produced 25% progeny exhibiting several zygotic phenotypes similar to those previously described in zebrafish and in the aforementioned pilot screen, as expected. Interestingly, new phenotypes such as golden yolk, no trunk, and short tail were observed. The siblings of sterile F2 mutants were used to produce an F3 generation in order to confirm familial sterility. Out of the 284 F3 fish belonging to 10 previously identified sterile families, 12 were found to be 1° males, 69 were wild-type, 83 sterile, and 120 were classified as */+ (either wild-type or carriers) with undefined genotypes. This screen provides proof of principle that K. marmoratus is a powerful vertebrate model for developmental genetics and can be used to identify mutations affecting fertility. PMID:26801648

  6. British Diabetic Association guidelines on genetic and immune screening for type 1 diabetes mellitus.

    PubMed

    Avery, L; Borsey, D Q; Greene, S A; Gummerson, I; Hayes, R; Kerr, D; Lean, M E; Marshall, S M; McInnes, A; Pierce, M; Roland, J; Sinclair, A J; Tadman, J; Walton, A; Wiles, P

    1998-08-01

    The following article is a report from the Chairman of the Professional Advisory Committee of the British Diabetic Association. The committee, with the help of a number of experts currently working in the field, produced a set of guidelines intended for use by health care professionals on the issues around genetic screening for Type 1 diabetes mellitus. The guidelines were approved by the Board of Management of the British Diabetic Association and we publish them here.

  7. A Genetic Mosaic Screen of Essential Zygotic Genes in Caenorhabditis Elegans

    PubMed Central

    Bucher, E. A.; Greenwald, I.

    1991-01-01

    We have devised a simple genetic mosaic screen, which circumvents the difficulties posed by phenotypic analysis of early lethal mutants, to analyze essential zygotic genes in Caenorhabditis elegans. The screen attempts to distinguish genes involved in cell type and/or lineage specific processes such as determination, differentiation or morphogenesis from genes involved in general processes such as intermediary metabolism by using the pattern of gene function to classify genes: genes required in one or a subset of early blastomeres may have specific functions, whereas genes required in all early blastomeres may have general functions. We found that 12 of 17 genes examined function in specific early blastomeres, suggesting that many zygotic genes contribute to specific early processes. We discuss the advantages and limitations of this screen, which is applicable to other regions of the C. elegans genome. PMID:2071016

  8. Statement of The American Society of Human Genetics on cystic fibrosis carrier screening

    SciTech Connect

    Not Available

    1992-12-01

    The identification in 1989 of the cystic fibrosis (CF) gene and its most common mutation immediately raised the possibility of CF carrier detection by DNA analysis. The American Society of Human Genetics (ASHG) issued a statement recommending that CF carrier testing should be made available to individuals with a family history of CF. It was also stated that screening of individuals or couples in the general population should not be offered until the rate of CF carrier detection improves. An additional prerequisite emphasized the need for the establishment of effective educational and counseling programs consistent with previous widely accepted principles. An NIH workshop reached similar conclusions. ASHG recommendations are that screening be limited to individuals with a family history of CF, testing should be accompanied by education and counseling, screening should be voluntary and confidential with appropriate laboratory quality controls, and efforts should be expanded to educate health care providers and the public.

  9. Newborn screening for SCID identifies patients with ataxia telangiectasia.

    PubMed

    Mallott, Jacob; Kwan, Antonia; Church, Joseph; Gonzalez-Espinosa, Diana; Lorey, Fred; Tang, Ling Fung; Sunderam, Uma; Rana, Sadhna; Srinivasan, Rajgopal; Brenner, Steven E; Puck, Jennifer

    2013-04-01

    Severe combined immunodeficiency (SCID) is characterized by failure of T lymphocyte development and absent or very low T cell receptor excision circles (TRECs), DNA byproducts of T cell maturation. Newborn screening for TRECs to identify SCID is now performed in several states using PCR of DNA from universally collected dried blood spots (DBS). In addition to infants with typical SCID, TREC screening identifies infants with T lymphocytopenia who appear healthy and in whom a SCID diagnosis cannot be confirmed. Deep sequencing was employed to find causes of T lymphocytopenia in such infants. Whole exome sequencing and analysis were performed in infants and their parents. Upon finding deleterious mutations in the ataxia telangiectasia mutated (ATM) gene, we confirmed the diagnosis of ataxia telangiectasia (AT) in two infants and then tested archival newborn DBS of additional AT patients for TREC copy number. Exome sequencing and analysis led to 2 unsuspected gene diagnoses of AT. Of 13 older AT patients for whom newborn DBS had been stored, 7 samples tested positive for SCID under the criteria of California's newborn screening program. AT children with low neonatal TRECs had low CD4 T cell counts subsequently detected (R = 0.64). T lymphocytopenia in newborns can be a feature of AT, as revealed by TREC screening and exome sequencing. Although there is no current cure for the progressive neurological impairment of AT, early detection permits avoidance of infectious complications, while providing information for families regarding reproductive recurrence risks and increased cancer risks in patients and carriers.

  10. Mouse models of cancer: Sleeping Beauty transposons for insertional mutagenesis screens and reverse genetic studies.

    PubMed

    Tschida, Barbara R; Largaespada, David A; Keng, Vincent W

    2014-03-01

    The genetic complexity and heterogeneity of cancer has posed a problem in designing rationally targeted therapies effective in a large proportion of human cancer. Genomic characterization of many cancer types has provided a staggering amount of data that needs to be interpreted to further our understanding of this disease. Forward genetic screening in mice using Sleeping Beauty (SB) based insertional mutagenesis is an effective method for candidate cancer gene discovery that can aid in distinguishing driver from passenger mutations in human cancer. This system has been adapted for unbiased screens to identify drivers of multiple cancer types. These screens have already identified hundreds of candidate cancer-promoting mutations. These can be used to develop new mouse models for further study, which may prove useful for therapeutic testing. SB technology may also hold the key for rapid generation of reverse genetic mouse models of cancer, and has already been used to model glioblastoma and liver cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. [Biochemical screening and genetic diagnosis of thalassemia in children from Kunming].

    PubMed

    Wen, Bai-Ping; Fan, Mao; Dai, Hong-Jian; Zhuang, Yu; Liu, Hong-Ling; Yang, Jun-Yi; Yang, Xiao-Hong; Deng, Wen-Guo

    2011-02-01

    To investigate the types and frequency of gene mutations in children with thalassemia in Kunming, Yunan Province. A biochemical screening for thalassemia was performed by testing RBC fragility, MCV and hemoglobin electrophoresis on 1338 children from Kunming, Yunnan Province. Genetic diagnosis was performed on the children with α-thalassemia by gap-PCR and on the children with β-thalassemia by PCR-RDB. The positive rate of the biochemical screening for thalassemia was 11.36% (152 cases). The positive rate of genetic diagnosis was 8.59% (115 cases). Of the 115 cases, α-thalassemia was found in 43 cases, β-thalassemia in 68 cases and α-combined-β thalassemia in 4 cases.--SEA/αα accounted for 47%, -α4.2/αα accounted for 21%, and HbH disease accounted for 14%. Six genotypes were found in 68 cases of β-thalassemia and the mutation frequency of βE was the highest (32%), followed by CD41-42 (24%), CD17 (23%), IVS-II654 (10%), CD71-72 (10%), and -28 (1%). The frequency of gene mutations for thalassemia is high in children from Kunming, Yunnan Province. Premarital and prenatal screenings and genetic diagnosis for thalassemia should be carried out in this area.

  12. Detection of biotinidase gene mutations in Turkish patients ascertained by newborn and family screening.

    PubMed

    Karaca, Mehmet; Özgül, Rıza Köksal; Ünal, Özlem; Yücel-Yılmaz, Didem; Kılıç, Mustafa; Hişmi, Burcu; Tokatlı, Ayşegül; Coşkun, Turgay; Dursun, Ali; Sivri, Hatice Serap

    2015-08-01

    The incidence of biotinidase deficiency in Turkey is currently one of the highest in the world. To expand upon the information about the biotinidase gene (BTD) variations in Turkish patients, we conducted a mutation screening in a large series (n = 210) of probands with biotinidase deficiency, using denaturing high-performance liquid chromatography and direct DNA sequencing. The putative effects of novel mutations were predicted by computational program. Twenty-six mutations, including six novels (p.C143F, p.T244I, c.1212-1222del11, c.1320delG, p.V457L, p.G480R) were identified. Nine of the patients were symptomatic at the initial clinical assessment with presentations of seizures, encephalopathy, and lactic acidemia. The most common mutation in this group of symptomatic patients was c.98-104 del7ins3. Among the screened patients, 72 have partial and 134 have profound biotinidase deficiency (BD) of which 106 are homozygous for BTD mutations. The common mutations (p.R157H, p.D444H, c.98-104del7ins3, p.T532M) cumulatively accounted for 72.3% of all the mutant alleles in the Turkish population. The identification of common mutations and hot spot regions of the BTD gene in Turkish patients is important for mutation screening in the Turkish population and helps to ascertain carriers, may have impact on genetic counseling and implementing prevention programs.

  13. Mismatch repair genes identified using genetic screens in Blm-deficient embryonic stem cells.

    PubMed

    Guo, Ge; Wang, Wei; Bradley, Allan

    2004-06-24

    Phenotype-driven recessive genetic screens in diploid organisms require a strategy to render the mutation homozygous. Although homozygous mutant mice can be generated by breeding, a reliable method to make homozygous mutations in cultured cells has not been available, limiting recessive screens in culture. Cultured embryonic stem (ES) cells provide access to all of the genes required to elaborate the fundamental components and physiological systems of a mammalian cell. Here we have exploited the high rate of mitotic recombination in Bloom's syndrome protein (Blm)-deficient ES cells to generate a genome-wide library of homozygous mutant cells from heterozygous mutations induced with a revertible gene trap retrovirus. We have screened this library for cells with defects in DNA mismatch repair (MMR), a system that detects and repairs base-base mismatches. We demonstrate the recovery of cells with homozygous mutations in known and novel MMR genes. We identified Dnmt1(ref. 5) as a novel MMR gene and confirmed that Dnmt1-deficient ES cells exhibit micro-satellite instability, providing a mechanistic explanation for the role of Dnmt1 in cancer. The combination of insertional mutagenesis in Blm-deficient ES cells establishes a new approach for phenotype-based recessive genetic screens in ES cells.

  14. Screening of male patients with autism spectrum disorder for creatine transporter deficiency.

    PubMed

    Newmeyer, A; deGrauw, T; Clark, J; Chuck, G; Salomons, G

    2007-12-01

    Creatine deficiency syndromes (CDS) are newly identified genetic disorders that result in neurological impairment of cognition and communication. The purpose of our study was to screen 100 male subjects with autism spectrum disorder for mutations in the SLC6A8 gene in order to determine the frequency of this genetic disorder in this population. One hundred males ages 3-18 years diagnosed with autism spectrum disorder based on DSM-IV criteria were recruited. DNA sequence analysis was performed on all subjects for creatine transporter gene (SLC6A8) defects. One subject had a novel unclassified variant in the SLC6A8 gene exon 13: c.1890G>C. Given that autistic features are found in a number of patients with CDS, SLC6A8 deficiency as well as the treatable forms of CDS should be included in the differential diagnosis of patients with autism spectrum disorder.

  15. Nutritional screening in hospitalized pediatric patients: a systematic review.

    PubMed

    Teixeira, Adriana Fonseca; Viana, Kátia Danielle Araújo Lourenço

    2016-01-01

    This systematic review aimed to verify the available scientific evidence on the clinical performance and diagnostic accuracy of nutritional screening tools in hospitalized pediatric patients. A search was performed in the Medline (National Library of Medicine United States), LILACS (Latin American and Caribbean Health Sciences), PubMed (US National Library of Medicine National Institutes of Health), in the SCIELO (Scientific Electronic Library Online), through CAPES portal (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), bases Scopus e Web of Science. The descriptors used in accordance with the Descriptors in Health Sciences (DeCS)/Medical Subject Headings (MeSH) list were "malnutrition", "screening", and "pediatrics", as well as the equivalent words in Portuguese. The authors identified 270 articles published between 2004 and 2014. After applying the selection criteria, 35 were analyzed in full and eight articles were included in the systematic review. We evaluated the methodological quality of the studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). Five nutritional screening tools in pediatrics were identified. Among these, the Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) showed high sensitivity, almost perfect inter-rater agreement and between the screening and the reference standard; the Screening Tool Risk on Nutritional Status and Growth (STRONGkids) showed high sensitivity, lower percentage of specificity, substantial intra-rater agreement, and ease of use in clinical practice. The studies included in this systematic review showed good performance of the nutritional screening tools in pediatrics, especially STRONGkids and STAMP. The authors emphasize the need to perform for more studies in this area. Only one tool was translated and adapted to the Brazilian pediatric population, and it is essential to carry out studies of tool adaptation and validation for this population. Copyright

  16. Patient difficulty using tablet computers to screen in primary care.

    PubMed

    Hess, Rachel; Santucci, Aimee; McTigue, Kathleen; Fischer, Gary; Kapoor, Wishwa

    2008-04-01

    Patient-administered computerized questionnaires represent a novel tool to assist primary care physicians in the delivery of preventive health care. The aim of this study was to assess patient-reported ease of use with a self-administered tablet computer-based questionnaire in routine clinical care. All patients seen in a university-based primary care practice were asked to provide routine screening information using a touch-screen tablet computer-based questionnaire. Patients reported difficulty using the tablet computer after completion of their first questionnaire. Ten thousand nine hundred ninety-nine patients completed the questionnaire between January 2004 and January 2006. We calculated rates of reporting difficulty (no difficulty, some difficulty, or a lot of difficulty) using the tablet computers based on patient age, sex, race, educational attainment, marital status, and number of comorbid medical conditions. We constructed multivariable ordered logistic models to identify predictors of increased self-reported difficulty using the computer. The majority of patients (84%) reported no difficulty using the tablet computers to complete the questionnaire, with only 3% reporting a lot of difficulty. Significant predictors of reporting more difficulty included increasing age [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.05-1.05)]; Asian race (OR 2.3, 95% CI 1.8-2.9); African American race (OR 1.4, 95% CI 1.2-1.6); less than a high school education (OR 3.0, 95% CI 2.6-3.4); and the presence of comorbid medical conditions (1-2: OR 1.3, 95% CI 1.2-1.5; > or =3: OR 1.7 95% CI 1.5-2.1). The majority of primary care patients reported no difficulty using a self-administered tablet computer-based questionnaire. While computerized questionnaires present opportunities to collect routine screening information from patients, attention must be paid to vulnerable groups.

  17. Extended screening for major mitochondrial DNA point mutations in patients with hereditary hearing loss.

    PubMed

    Kato, Tomofumi; Nishigaki, Yutaka; Noguchi, Yoshihiro; Fuku, Noriyuki; Ito, Taku; Mikami, Eri; Kitamura, Ken; Tanaka, Masashi

    2012-12-01

    Hearing loss (HL) is the most common sensory disorder in humans. Many patients with mitochondrial diseases have sensorineural HL (SNHL). The HL of these patients manifests as a consequence of either syndromic or nonsyndromic mitochondrial diseases. Furthermore, the phenotypes vary among patients even if they are carrying the same mutation. Therefore, these features make it necessary to analyze every presumed mutation in patients with hereditary HL, but the extensive analysis of various mutations is laborious. We analyzed 373 patients with suspected hereditary HL by using an extended suspension-array screening system for major mitochondrial DNA (mtDNA) mutations, which can detect 32 other mtDNA mutations in addition to the previously analyzed 29 mutations. In the present study, we detected 2 different mtDNA mutations among these 373 patients; m.7444G>A in the MT-CO1 gene and m.7472insC in the MT-TS1 gene in 1 patient (0.3%) for each. As these two patients had no clinical features other than HL, they had not been suspected of having mtDNA mutations. This extended screening system together with the previous one is useful for the genetic diagnosis and epidemiological study of both syndromic and nonsyndromic HL.

  18. A Novel Forward Genetic Screen for Identifying Mutations Affecting Larval Neuronal Dendrite Development in Drosophila melanogaster

    PubMed Central

    Medina, Paul Mark B.; Swick, Lance L.; Andersen, Ryan; Blalock, Zachary; Brenman, Jay E.

    2006-01-01

    Vertebrate and invertebrate dendrites are information-processing compartments that can be found on both central and peripheral neurons. Elucidating the molecular underpinnings of information processing in the nervous system ultimately requires an understanding of the genetic pathways that regulate dendrite formation and maintenance. Despite the importance of dendrite development, few forward genetic approaches have been used to analyze the latest stages of dendrite development, including the formation of F-actin-rich dendritic filopodia or dendritic spines. We developed a forward genetic screen utilizing transgenic Drosophila second instar larvae expressing an actin, green fluorescent protein (GFP) fusion protein (actin∷GFP) in subsets of sensory neurons. Utilizing this fluorescent transgenic reporter, we conducted a forward genetic screen of >4000 mutagenized chromosomes bearing lethal mutations that affected multiple aspects of larval dendrite development. We isolated 13 mutations on the X and second chromosomes composing 11 complementation groups affecting dendrite outgrowth/branching, dendritic filopodia formation, or actin∷GFP localization within dendrites in vivo. In a fortuitous observation, we observed that the structure of dendritic arborization (da) neuron dendritic filopodia changes in response to a changing environment. PMID:16415365

  19. Misunderstandings Concerning Genetics Among Patients Confronting Genetic Disease

    PubMed Central

    Klitzman, Robert L.

    2010-01-01

    Critical questions arise about misunderstandings of genetics. We interviewed for 2 h each, 64 individuals who had or were at risk for Huntington’s disease (HD), breast cancer or Alpha-1 antitrypsin deficiency. These individuals revealed various misunderstandings that can affect coping, and testing, treatment and reproductive decisions. A therapeutic misconception about testing appeared: that testing would be helpful in and of itself. Many believed they could control genetic disorders (even HD), yet these beliefs were often incorrect, and could impede coping, testing, and treatment. Misunderstandings about statistics and genetics often fueled each other, and reflected denial, and desires for hope and control. Emotional needs can thus outweigh understandings of genetics and statistics, and providers’ input. Individuals often maintained non-scientific beliefs, though embarrassed by these. These data have implications for care, and public and professional education. Misunderstandings’ persistence, despite realization of their inaccuracy, suggests that providers need to address not just cognitive facts, but underlying emotional issues. PMID:20512408

  20. Axon regeneration pathways identified by systematic genetic screening in C. elegans.

    PubMed

    Chen, Lizhen; Wang, Zhiping; Ghosh-Roy, Anindya; Hubert, Thomas; Yan, Dong; O'Rourke, Sean; Bowerman, Bruce; Wu, Zilu; Jin, Yishi; Chisholm, Andrew D

    2011-09-22

    The mechanisms underlying the ability of axons to regrow after injury remain poorly explored at the molecular genetic level. We used a laser injury model in Caenorhabditis elegans mechanosensory neurons to screen 654 conserved genes for regulators of axonal regrowth. We uncover several functional clusters of genes that promote or repress regrowth, including genes classically known to affect axon guidance, membrane excitability, neurotransmission, and synaptic vesicle endocytosis. The conserved Arf Guanine nucleotide Exchange Factor (GEF), EFA-6, acts as an intrinsic inhibitor of regrowth. By combining genetics and in vivo imaging, we show that EFA-6 inhibits regrowth via microtubule dynamics, independent of its Arf GEF activity. Among newly identified regrowth inhibitors, only loss of function in EFA-6 partially bypasses the requirement for DLK-1 kinase. Identification of these pathways significantly expands our understanding of the genetic basis of axonal injury responses and repair.

  1. A Fluorescence-Based Genetic Screen to Study Retinal Degeneration in Drosophila

    PubMed Central

    Wang, Tao

    2015-01-01

    The Drosophila visual system has been proved to be a powerful genetic model to study eye disease such as retinal degeneration. Here, we describe a genetic method termed “Rh1::GFP ey-flp/hid” that is based on the fluorescence of GFP-tagged major rhodopsin Rh1 in the eyes of living flies and can be used to monitor the integrity of photoreceptor cells. Through combination of this method and ERG recording, we examined a collection of 667 mutants and identified 18 genes that are required for photoreceptor cell maintenance, photoresponse, and rhodopsin synthesis. Our findings demonstrate that this “Rh1::GFP ey-flp/hid” method enables high-throughput F1 genetic screens to rapidly and precisely identify mutations of retinal degeneration. PMID:26659849

  2. Gestational surrogacy and the role of routine embryo screening: Current challenges and future directions for preimplantation genetic testing.

    PubMed

    Sills, E Scott; Anderson, Robert E; McCaffrey, Mary; Li, Xiang; Arrach, Nabil; Wood, Samuel H

    2016-03-01

    Preimplantation genetic screening (PGS) is a component of IVF entailing selection of an embryo for transfer on the basis of chromosomal normalcy. If PGS were integrated with single embryo transfer (SET) in a surrogacy setting, this approach could improve pregnancy rates, minimize miscarriage risk, and limit multiple gestations. Even without PGS, pregnancy rates for IVF surrogacy cases are generally satisfactory, especially when treatment utilizes embryos derived from young oocytes and transferred to a healthy surrogate. However, there could be a more general role for PGS in surrogacy, since background aneuploidy in embryos remains a major factor driving implantation failure and miscarriage for all infertility patients. At present, the proportion of IVF cases involving GS is limited, while the number of IVF patients requesting PGS appears to be increasing. In this report, the relevance of PGS for surrogacy in the rapidly changing field of assisted fertility medicine is discussed. © 2015 Wiley Periodicals, Inc.

  3. Neonatal screening for glucose-6-phosphate dehydrogenase deficiency: biochemical versus genetic technologies.

    PubMed

    Kaplan, Michael; Hammerman, Cathy

    2011-06-01

    Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, a commonly occurring genetic condition, is associated in neonates with severe hemolytic episodes, extreme hyperbilirubinemia, and bilirubin encephalopathy. Neonatal screening programs for the condition should increase parental and caretaker awareness, thereby facilitating early access to treatment with resultant diminished mortality and morbidity. However, screening for G-6-PD deficiency is not widely performed. Although G-6-PD-deficient males may be accurately identified, females are more difficult to categorize because many in this group may be heterozygotes with phenotype overlap between normal homozygotes, heterozygotes, and deficient homozygotes. Screening methodologies include biochemical qualitative assays, quantitative enzymatic activity measurements and DNA-based polymerase chain reaction molecular screening. The appropriateness of any of these technologies for any particular population group or geographic area must be assessed before setting up a screening program. The pros and cons of each method, including ease of testing, cost, need for sophisticated laboratory equipment and degree of personnel training, as well as the ability to identify females, are discussed.

  4. Patient attitudes and issues in colon cancer screening.

    PubMed

    Early, Dayna S; Gray, Darrell M

    2014-05-01

    Colorectal cancer (CRC) is the third leading cause of cancer death in the United States, and is largely preventable by CRC screening (CRCS). Participation in CRCS, however, is much lower than participation in other forms of preventive care. Many reasons for low rates of participation have been identified, and can be generally divided into provider- and patient-specific issues. Lack of a provider recommendation is a well-established and widely reported patient barrier to CRCS. Numerous patient-specific issues have been identified, ranging from fear of CRCS test results to lack of knowledge about individual risk for CRC and inadequate resources to complete CRCS. This article discusses the impact of patient attitudes and issues toward CRCS, with particular attention to modifiable psychosocial factors, the importance of patient preferences for one CRCS test over another, knowledge of CRC risk, and the impact of educational tools on patient compliance with CRCS.

  5. Postmortem genetic screening for the identification, verification, and reporting of genetic variants contributing to the sudden death of the young

    PubMed Central

    Methner, D. Nicole R.; Scherer, Steven E.; Welch, Katherine; Walkiewicz, Magdalena; Eng, Christine M.; Belmont, John W.; Powell, Mark C.; Korchina, Viktoriya; Doddapaneni, Harsha Vardhan; Muzny, Donna M.; Gibbs, Richard A.; Wolf, Dwayne A.; Sanchez, Luis A.; Kahn, Roger

    2016-01-01

    Each year in the United States, thousands of cases of sudden and unexpected deaths of infants, children, and young adults are assigned an undetermined cause of death after postmortem investigation and autopsy. Heritable genetic variants have been suggested as the cause of up to a third of sudden death (SD) cases. Elucidation of the genetic variants involved in SD cases is important to not only help establish cause and manner of death of these individuals, but to also aid in determining whether familial genetic testing should be considered. Previously, these types of postmortem screenings have not been a feasible option for most county medical examiners’ and coroners’ offices. We sequenced full exons of 64 genes associated with SD in the largest known cohort (351) of infant and young SD decedents using massively parallel sequencing at <$600 per sample. Genetic variants were assessed through literature review and clinical evaluation by a multidisciplinary consortium of experts. Thirteen individuals (3.7%), eight infants (2.8% of those <1 yr of age) and five children/young adults (7.0% of those >1 yr of age), were found to have a reportable genetic variant contributing to SD. These percentages represent an estimate lower than those previously reported. Overall yields and results likely vary between studies due to differences in evaluation techniques and reporting. Additionally, we recommend ongoing assessment of data, including nonreported novel variants, as technology and literature continually advance. This study demonstrates a strategy to implement molecular autopsies in medicolegal investigations of young SD decedents. PMID:27435932

  6. Body Image Screening for Cancer Patients Undergoing Reconstructive Surgery

    PubMed Central

    Fingeret, Michelle Cororve; Nipomnick, Summer; Guindani, Michele; Baumann, Donald; Hanasono, Matthew; Crosby, Melissa

    2014-01-01

    Objectives Body image is a critical issue for cancer patients undergoing reconstructive surgery, as they can experience disfigurement and functional impairment. Distress related to appearance changes can lead to various psychosocial difficulties, and patients are often reluctant to discuss these issues with their healthcare team. Our goals were to design and evaluate a screening tool to aid providers in identifying patients who may benefit from referral for specialized psychosocial care to treat body image concerns. Methods We designed a brief 4-item instrument and administered it at a single time point to cancer patients who were undergoing reconstructive treatment. We used simple and multinomial regression models to evaluate whether survey responses, demographic, or clinical variables predicted interest and enrollment in counseling. Results Over 95% of the sample (n = 248) endorsed some concerns, preoccupation, or avoidance due to appearance changes. Approximately one-third of patients were interested in obtaining counseling or additional information to assist with body image distress. Each survey item significantly predicted interest and enrollment in counseling. Concern about future appearance changes was the single best predictor of counseling enrollment. Sex, age, and cancer type were not predictive of counseling interest or enrollment. Conclusions We present initial data supporting use of the Body Image Screener for Cancer Reconstruction. Our findings suggest benefits of administering this tool to patients presenting for reconstructive surgery. It is argued that screening and treatment for body image distress should be provided to this patient population at the earliest possible time point. PMID:25066586

  7. Genetic screening, health care and the insurance industry. Should genetic information be made available to insurers?

    PubMed

    Ossa, Diego F; Towse, Adrian

    2004-06-01

    The potential use of genetic tests in insurance has raised concerns about discrimination and individuals losing access to health care either because of refusals to test for treatable diseases, or because test-positives cannot afford premiums. Governments have so far largely sought to restrict the use of genetic information by insurance companies. To date the number of tests available with significant actuarial value is limited. However, this is likely to change, raising more clearly the question as to whether the social costs of adverse selection outweigh the social costs of individuals not accessing health care for fear of the consequences of test information being used in insurance markets. In this contribution we set out the policy context and model the potential trade-offs between the losses faced by insurers from adverse selection by insurees (which will increase premiums reducing consumer welfare) and the detrimental health effects that may result from persons refusing to undergo tests that could identify treatable health conditions. It argues that the optimal public policy on genetic testing should reflect overall societal benefit, taking account of these trade-offs. Based on our model, the factors that influence the outcome include: the size of and value attached to the health gains from treatment; deterrent effects of a disclosure requirement on testing for health reasons; incidence of the disease; propensity of test-positives to adverse select; policy value adverse selectors buy in a non-disclosure environment; and price elasticity of demand for insurance. Our illustrative model can be used as a benchmark for developing other scenarios or incorporating real data in order to address the impact of different policies on disclosure and requirement to test.

  8. A model of genetic guidance for hemoglobinopathy patients and laboratory diagnosis of family members as educational and preventive measures

    PubMed Central

    Ferreira, Tatiana Dela-Sávia; Freire, Adriana Sousa; Silveira-Lacerda, Elisângela de Paula; García-Zapata, Marco Túlio Antônio

    2012-01-01

    Background: The high frequency of hemoglobinopathies in Brazil constitutes a public health problem and thus educational and preventive measures are necessary to reduce the incidence. Genetic guidance, a modality of genetic counseling, and family screening are measures that can assist in reproductive decisions and mitigate clinical, psychological and social problems of families with these disorders. Objetive: The objective of the current study was to evaluate the effectiveness of educational and preventive measures for hemoglobinopathies using genetic guidance and laboratory screening of families. Methods: The diagnoses of patients with hemoglobinopathies were confirmed and then the level of knowledge about their disease was evaluated and genetic guidance was provided. Three months later, the level of assimilated information of these patients was evaluated. In addition, laboratory diagnosis of family members was carried out. Results: Diagnosis of sickle cell anemia was confirmed for most patients. Moreover, the majority of the patients who had a low level of knowledge before genetic guidance (68.8%) demonstrated a higher level of assimilated information after the process (81.8%). Almost 70% of the family members had hemoglobin changes and some had hemoglobinopathies(2.6%). They were duly informed about the results of the examinations, which made it possible to investigate further. Conclusion: Genetic guidance and family screening were effective preventive and educational measures that improved the quality of life of patients, preventing complications and sequels and allowed the referral of those who may transmit altered genes for clinical diagnosis and to genetic counseling services. PMID:23125541

  9. Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies

    PubMed Central

    Carreño, Oriel; Corominas, Roser; Serra, Selma Angèlica; Sintas, Cèlia; Fernández-Castillo, Noèlia; Vila-Pueyo, Marta; Toma, Claudio; Gené, Gemma G; Pons, Roser; Llaneza, Miguel; Sobrido, María-Jesús; Grinberg, Daniel; Valverde, Miguel Ángel; Fernández-Fernández, José Manuel; Macaya, Alfons; Cormand, Bru

    2013-01-01

    Hemiplegic migraine (HM) is a rare and severe subtype of autosomal dominant migraine, characterized by a complex aura including some degree of motor weakness. Mutations in four genes (CACNA1A, ATP1A2, SCN1A and PRRT2) have been detected in familial and in sporadic cases. This genetically and clinically heterogeneous disorder is often accompanied by permanent ataxia, epileptic seizures, mental retardation, and chronic progressive cerebellar atrophy. Here we report a mutation screening in the CACNA1A and ATP1A2 genes in 18 patients with HM. Furthermore, intragenic copy number variant (CNV) analysis was performed in CACNA1A using quantitative approaches. We identified four previously described missense CACNA1A mutations (p.Ser218Leu, p.Thr501Met, p.Arg583Gln, and p.Thr666Met) and two missense changes in the ATP1A2 gene, the previously described p.Ala606Thr and the novel variant p.Glu825Lys. No structural variants were found. This genetic screening allowed the identification of more than 30% of the disease alleles, all present in a heterozygous state. Functional consequences of the CACNA1A-p.Thr501Met mutation, previously described only in association with episodic ataxia, and ATP1A2-p.Glu825Lys, were investigated by means of electrophysiological studies, cell viability assays or Western blot analysis. Our data suggest that both these variants are disease-causing. PMID:24498617

  10. The role of genetic factors in patients with hepatocellular carcinoma and iron overload - a prospective series of 234 patients.

    PubMed

    Funakoshi, Natalie; Chaze, Iphigénie; Alary, Anne-Sophie; Tachon, Gaëlle; Cunat, Séverine; Giansily-Blaizot, Muriel; Bismuth, Michael; Larrey, Dominique; Pageaux, Georges-Philippe; Schved, Jean-François; Donnadieu-Rigole, Hélène; Blanc, Pierre; Aguilar-Martinez, Patricia

    2016-05-01

    Iron overload (IO) in HFE-related hereditary haemochromatosis is associated with increased risk of liver cancer. This study aimed to investigate the role of other genes involved in hereditary IO among patients with hepatocellular carcinoma (HCC). Patients with HCC diagnosed in our institution were included in this prospective study. Those with ferritin levels ≥300 μg/L (males) or ≥200 μg/L (females) and/or transferrin saturation ≥50% (males) or ≥45% (females) had liver iron concentration (LIC) evaluated by MRI. HFE C282Y and H63D mutations were screened. Genetic analyses of genes involved in hereditary IO (HFE, HJV/HFE2, HAMP, TFR2, SLC40A1, GNPAT) were performed in patients with increased LIC. A total of 234 patients were included; 215 (92%) had common acquired risk factors of HCC (mainly alcoholism or chronic viral hepatitis). 119 patients had abnormal iron parameters. Twelve (5.1%) were C282Y homozygotes, three were compound C282Y/H63D heterozygotes. LIC was measured by MRI in 100 patients. Thirteen patients with a LIC>70 μmol/g were enrolled in further genetic analyses: two unrelated patients bore the HAMP:c.-153C>T mutation at the heterozygous state, which is associated with increased risk of IO and severe haemochromatosis. Specific haplotypes of SLC40A1 were also studied. Additional genetic risk factors of IO were found in 18 patients (7.7%) among a large series of 234 HCC patients. Screening for IO and the associated at-risk genotypes in patients who have developed HCC, is useful for both determining etiologic diagnosis and enabling family screening and possibly primary prevention in relatives. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Identification of common genetic modifiers of neurodegenerative diseases from an integrative analysis of diverse genetic screens in model organisms.

    PubMed

    Chen, Xi; Burgoyne, Robert D

    2012-02-14

    An array of experimental models have been developed in the small model organisms C. elegans, S. cerevisiae and D. melanogaster for the study of various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and expanded polyglutamine diseases as exemplified by Huntington's disease (HD) and related ataxias. Genetic approaches to determine the nature of regulators of the disease phenotypes have ranged from small scale to essentially whole genome screens. The published data covers distinct models in all three organisms and one important question is the extent to which shared genetic factors can be uncovered that affect several or all disease models. Surprisingly it has appeared that there may be relatively little overlap and that many of the regulators may be organism or disease-specific. There is, however, a need for a fully integrated analysis of the available genetic data based on careful comparison of orthologues across the species to determine the real extent of overlap. We carried out an integrated analysis using C. elegans as the baseline model organism since this is the most widely studied in this context. Combination of data from 28 published studies using small to large scale screens in all three small model organisms gave a total of 950 identifications of genetic regulators. Of these 624 were separate genes with orthologues in C. elegans. In addition, 34 of these genes, which all had human orthologues, were found to overlap across studies. Of the common genetic regulators some such as chaperones, ubiquitin-related enzymes (including the E3 ligase CHIP which directly links the two pathways) and histone deacetylases were involved in expected pathways whereas others such as the peroxisomal acyl CoA-oxidase suggest novel targets for neurodegenerative disease therapy We identified a significant number of overlapping regulators of neurodegenerative disease models. Since the diseases have, as an underlying feature, protein aggregation

  12. Screening for suicide ideation among older primary care patients.

    PubMed

    Heisel, Marnin J; Duberstein, Paul R; Lyness, Jeffrey M; Feldman, Mitchell D

    2010-01-01

    Older adults have high rates of suicide and typically seek care in primary medical practices. Older adults often do not directly or spontaneously report thoughts of suicide, which can impede suicide prevention efforts. Therefore, the use of additional approaches to suicide risk detection is needed, including the use of screening tools. The objective of this study was to assess whether brief screens for depression have acceptable operating characteristics in identifying suicide ideation among older primary care patients and to examine potential sex differences in the screen's accuracy. We administered the 15-item Geriatric Depression Scale (GDS), which includes a 5-item GDS subscale (GDS-SI) designed to screen for suicide ideation, to a cross-sectional cohort of 626 primary care patients (235 men, 391 women) 65 years of age or older in the Northeastern United States. We assessed presence of suicide ideation with items from the Hamilton Rating Scale for Depression and the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Patients expressing suicide ideation (n = 69) scored higher on the GDS and GDS-SI than those who did not (n = 557). A GDS cut score of 4 maximized sensitivity (0.754) and specificity (0.815), producing an area under the curve of 0.844 (P < .001) and positive and negative predictive values of 0.335 and 0.964, respectively. Optimal cut scores were 5 for men and 3 for women. A GDS-SI cut score of 1 was optimal for the total sample and for both men and women. The GDS and GDS-SI accurately identify older patients with suicide ideation. Research is needed to examine their acceptability and barriers to routine use in primary care.

  13. Screening for depression and anxiety in adolescent cancer patients.

    PubMed

    Kersun, Leslie S; Rourke, Mary T; Mickley, Megan; Kazak, Anne E

    2009-11-01

    The goals of this study were to evaluate the feasibility of depression and anxiety screening in on-therapy adolescents with cancer, determine the prevalence of depression and anxiety in this sample, and assess the concordance between patient and oncologist report of patient symptoms. Forty-one adolescents (ages 12 to 18 y) undergoing cancer therapy in an outpatient oncology clinic completed the Beck Youth Inventory II (BYI II) Depression and Anxiety scales. Treating oncologists independently rated patient depression and anxiety. Ninety-eight percent of patients agreed to participate and average time to measure completion was <15 minutes. Mean T-scores for the BDI-Y (Depression module) and BAI-Y (Anxiety module) for most were not different than published norms. Three and 2 patients scored in the moderate-extremely elevated range of the BAI-Y and BDI-Y, respectively. There were no associations between scores and sex, age, diagnosis, time since diagnosis, or treatment intensity. A depression and anxiety-screening program is feasible in the outpatient pediatric oncology setting. Rates of adolescent self-reported anxiety and depression are low, although oncologists perceived more patient distress. This is an area for future investigation.

  14. Screening haematology patients for carbapenem-resistant Klebsiella pneumoniae

    PubMed Central

    Kilgour, Elizabeth; Dunn, Caroline; Thomas, Linda; Fox, Richard; Mitchell, Lindsay; Paterson, Pamela

    2013-01-01

    Following a cluster of haematology patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) septicaemia, we initiated screening for rectal carriage of CRKP and multidrug-resistant K. pneumoniae (MDRKP) in this patient group. Haematology inpatients submit a rectal swab once weekly. When plated onto chromogenic Brilliance™ UTI Agar (Oxoid), and incubated overnight with a 10 µg ertapenem disc (Oxoid), K. pneumoniae is identified and semi-automated antibiotic susceptibility testing is performed using the Vitek 2 analyser (Biomerieux). When no zone of inhibition occurs, immediate intervention through patient isolation and enhanced environmental cleaning can be instigated to control further spread while empirical antibiotic prescribing is adapted to take account of identified resistances. Over 2 years, six patients with CRKP and 20 patients with MDRKP were identified. These isolates were resistant to first-line empirical treatment choices for neutropenic sepsis and presented a clinical risk of treatment failure for sepsis post cytotoxic chemotherapy. We describe how this rectal screening methodology was developed and how the results influenced appropriate antibiotic prescribing, patient placement in single rooms and the cleaning of the ward environment to prevent person-to-person transmission of MDRKP and CRKP.

  15. Promoting cancer screening within the patient centered medical home.

    PubMed

    Sarfaty, Mona; Wender, Richard; Smith, Robert

    2011-01-01

    While consensus has grown that primary care is the essential access point in a high-performing health care system, the current model of primary care underperforms in both chronic disease management and prevention. The Patient Centered Medical Home model (PCMH) is at the center of efforts to reinvent primary care practice, and is regarded as the most promising approach to addressing the burden of chronic disease, improving health outcomes, and reducing health spending. However, the potential for the medical home to improve the delivery of cancer screening (and preventive services in general) has received limited attention in both conceptualization and practice. Medical home demonstrations to date have included few evidence-based preventive services in their outcome measures, and few have evaluated the effect of different payment models. Decreasing use of hospitals and emergency rooms and an emphasis on improving chronic care represent improvements in effective delivery of healthcare, but leave opportunities for reducing the burden of cancer untouched. Data confirm that what does or does not happen in the primary care setting has a substantial impact on cancer outcomes. Insofar as cancer is the leading cause of death before age 80, the PCMH model must prioritize adherence to cancer screening according to recommended guidelines, and systems, financial incentives, and reimbursements must be aligned to achieve that goal. This article explores capacities that are needed in the medical home model to facilitate the integration of cancer screening and other preventive services. These capacities include improved patient access and communication, health risk assessments, periodic preventive health exams, use of registries that store cancer risk information and screening history, ability to track and follow up on tests and referrals, feedback on performance, and payment models that reward cancer screening.

  16. [Screening of patient manual handling risk using the MAPO method].

    PubMed

    Battevi, N; Menoni, Olga; Alvarez-Casado, E

    2012-01-01

    International standards draw attention to the steps that risk assessment should follow to first identify hazards, then proceed to risk evaluation and lastly, if necessary, risk assessment. The same logic also applies to risk assessment of manual patient handling. To check appropriateness of approach to "risk evaluation" of manual patient handling using MAPO, a cross sectional study was carried out aimed at checking the relationship between this new risk assessment model (MAPO screening) and occurrence of acute low back pain. After proper training the MAPO screening method was used to assess risk of manual handling of patients in 31 wards, covering 411 exposed subjects employed in geriatric hospitals belonging to the UNEBA (National Union Institutions and Social Welfare Initiatives) of the Veneto Region. At the same time health data were collected on the occurrence of low back pain episodes during the last year both in the group of exposed subjects and in an external reference group (237 subjects). Risk and clinical assessment data were verified and checked by the EPM research unit. Logistic analysis was used as a method to evaluate the relationship between MAPO screening risk index and acute low back pain. Investigating the relationship between acute low back pain episodes and levels of MAPO screening index, carried out only on exposed subjects who reported working for at least 30 hours per week (N=178), showed definitely positive trends: for MAPO screening index of exposure levels between 1.51 and 5, OR were double (OR=2.22; IC 95% 0.88-5.63) whereas for index levels exceeding 5, OR were about 4 (OR=3.77; IC 95% 1.33-10.74). These results did not show significant differences when correcting the analysis for confounding factors such as gender and age classes. The results of the study indicate that the proposed method, "MAPO screening", can be a useful tool to estimate risk due to manual handling of patients and can also be used to test the efficacy of preventive

  17. Screening for depression in patients with diabetes mellitus.

    PubMed

    McHale, Mala; Hendrikz, Joan; Dann, Fiona; Kenardy, Justin

    2008-10-01

    The first aim of this study was to compare the effectiveness of four commonly used depression screening measures for medically ill populations in identifying depression within a diabetes sample. The second aim was to examine whether the inclusion of a measure for physical symptoms specific to diabetes is also necessary for a diagnosis of depression or alternatively whether any overlap would obscure the effect on the screening measure for depression. One hundred fifty patients with Type 2 diabetes in two large public hospital outpatient clinics completed a questionnaire which included the Center for Epidemiological Studies--Depression Scale (CES-D), the Silverstone Concise Assessment for Depression (SCAD), the Hospital Anxiety and Depression Scale (HADS), and the Depression in the Medically Ill (DMI) Questionnaire. Patient scores on these questionnaires were then assessed against their responses on the Composite International Diagnostic Interview Short Form and the Diabetes Symptom Checklist to determine their effectiveness. Logistic regression and receiver operating curves analysis, including areas under the curves, suggested selecting the CES-D, rather than the DMI-10, HADS or SCAD for screening for depression in a Type 2 diabetic patient. The CES-D performed well at predicting depression, had high sensitivity and specificity, and did not require the addition of diabetes symptoms to aid in diagnosis.

  18. Preferences for genetic testing for colorectal cancer within a population-based screening program: a discrete choice experiment

    PubMed Central

    Veldwijk, Jorien; Lambooij, Mattijs S; Kallenberg, Frank G J; van Kranen, Henk J; Bredenoord, Annelien L; Dekker, Evelien; Smit, Henriëtte A; de Wit, G Ardine

    2016-01-01

    This study explored individuals' preferences for genetic testing for colorectal cancer (CRC) in a screening situation and their willingness to participate in genetic testing for Lynch syndrome, familial adenomatous polyposis (FAP), and familial colorectal cancer (FCC). For that purpose, 532 respondents aged 55–65 years completed a Discrete Choice Experiment. Using panel latent class models, the preferences for two screening situation characteristics (the probability of being genetically predisposed and the probability of developing CRC) and screening test characteristics (the frequency of preventive colonoscopies and CRC survival) were estimated. Based on these preferences, respondents' willingness to participate in the three screening initiatives was estimated. Lower-educated respondents and respondents who express serious anxiety and worries found colonoscopy frequency and the probability of developing CRC relatively more important and survival relatively less important compared with higher-educated respondents and respondents who express no anxiety and worries. These differences in preferences resulted in opposite preferences for participation in FCC and FAP screening. In conclusion, the general population is willing to participate in genetic screening for CRC. If individuals are suspected of genetic or familial CRC, they should at least be informed about their increased risk of being genetically predisposed and about the importance of participating in all preventive follow-up colonoscopies in order to maximize survival. PMID:26036860

  19. Supporting patient screening to identify suitable clinical trials.

    PubMed

    Bucur, Anca; Van Leeuwen, Jasper; Chen, Njin-Zu; Claerhout, Brecht; De Schepper, Kristof; Perez-Rey, David; Alonso-Calvo, Raul; Pugliano, Lina; Saini, Kamal

    2014-01-01

    To support the efficient execution of post-genomic multi-centric clinical trials in breast cancer we propose a solution that streamlines the assessment of the eligibility of patients for available trials. The assessment of the eligibility of a patient for a trial requires evaluating whether each eligibility criterion is satisfied and is often a time consuming and manual task. The main focus in the literature has been on proposing different methods for modelling and formalizing the eligibility criteria. However the current adoption of these approaches in clinical care is limited. Less effort has been dedicated to the automatic matching of criteria to the patient data managed in clinical care. We address both aspects and propose a scalable, efficient and pragmatic patient screening solution enabling automatic evaluation of eligibility of patients for a relevant set of trials. This covers the flexible formalization of criteria and of other relevant trial metadata and the efficient management of these representations.

  20. When Should Genetic Testing Be Performed in Epilepsy Patients?

    PubMed Central

    2017-01-01

    This review is a summary of a talk presented at the 2015 American Epilepsy Society Annual Meeting. Its purposes are 1) to review developments in epilepsy genetics, 2) to discuss which groups of patients with epilepsy might benefit from genetic testing, and 3) to present a rational approach to genetic testing in epilepsy in the rapidly evolving era of genomic medicine. PMID:28331464

  1. A genome-wide CRISPR library for high-throughput genetic screening in Drosophila cells.

    PubMed

    Bassett, Andrew R; Kong, Lesheng; Liu, Ji-Long

    2015-06-20

    The simplicity of the CRISPR/Cas9 system of genome engineering has opened up the possibility of performing genome-wide targeted mutagenesis in cell lines, enabling screening for cellular phenotypes resulting from genetic aberrations. Drosophila cells have proven to be highly effective in identifying genes involved in cellular processes through similar screens using partial knockdown by RNAi. This is in part due to the lower degree of redundancy between genes in this organism, whilst still maintaining highly conserved gene networks and orthologs of many human disease-causing genes. The ability of CRISPR to generate genetic loss of function mutations not only increases the magnitude of any effect over currently employed RNAi techniques, but allows analysis over longer periods of time which can be critical for certain phenotypes. In this study, we have designed and built a genome-wide CRISPR library covering 13,501 genes, among which 8989 genes are targeted by three or more independent single guide RNAs (sgRNAs). Moreover, we describe strategies to monitor the population of guide RNAs by high throughput sequencing (HTS). We hope that this library will provide an invaluable resource for the community to screen loss of function mutations for cellular phenotypes, and as a source of guide RNA designs for future studies.

  2. A mosaic genetic screen for genes involved in the early steps of Drosophila oogenesis.

    PubMed

    Jagut, Marlène; Mihaila-Bodart, Ludivine; Molla-Herman, Anahi; Alin, Marie-Françoise; Lepesant, Jean-Antoine; Huynh, Jean-René

    2013-03-01

    The first hours of Drosophila embryogenesis rely exclusively on maternal information stored within the egg during oogenesis. The formation of the egg chamber is thus a crucial step for the development of the future adult. It has emerged that many key developmental decisions are made during the very first stages of oogenesis. We performed a clonal genetic screen on the left arm of chromosome 2 for mutations affecting early oogenesis. During the first round of screening, we scored for defects in egg chambers morphology as an easy read-out of early abnormalities. In a second round of screening, we analyzed the localization of centrosomes and Orb protein within the oocyte, the position of the oocyte within the egg chamber, and the progression through meiosis. We have generated a collection of 71 EMS-induced mutants that affect oocyte determination, polarization, or localization. We also recovered mutants affecting the number of germline cyst divisions or the differentiation of follicle cells. Here, we describe the analysis of nine complementation groups and eight single alleles. We mapped several mutations and identified alleles of Bicaudal-D, lethal(2) giant larvae, kuzbanian, GDP-mannose 4,6-dehydratase, tho2, and eiF4A. We further report the molecular identification of two alleles of the Drosophila homolog of Che-1/AATF and demonstrate its antiapoptotic activity in vivo. This collection of mutants will be useful to investigate further the early steps of Drosophila oogenesis at a genetic level.

  3. A Genome-Wide CRISPR Library for High-Throughput Genetic Screening in Drosophila Cells

    PubMed Central

    Bassett, Andrew R.; Kong, Lesheng; Liu, Ji-Long

    2015-01-01

    The simplicity of the CRISPR/Cas9 system of genome engineering has opened up the possibility of performing genome-wide targeted mutagenesis in cell lines, enabling screening for cellular phenotypes resulting from genetic aberrations. Drosophila cells have proven to be highly effective in identifying genes involved in cellular processes through similar screens using partial knockdown by RNAi. This is in part due to the lower degree of redundancy between genes in this organism, whilst still maintaining highly conserved gene networks and orthologs of many human disease-causing genes. The ability of CRISPR to generate genetic loss of function mutations not only increases the magnitude of any effect over currently employed RNAi techniques, but allows analysis over longer periods of time which can be critical for certain phenotypes. In this study, we have designed and built a genome-wide CRISPR library covering 13,501 genes, among which 8989 genes are targeted by three or more independent single guide RNAs (sgRNAs). Moreover, we describe strategies to monitor the population of guide RNAs by high throughput sequencing (HTS). We hope that this library will provide an invaluable resource for the community to screen loss of function mutations for cellular phenotypes, and as a source of guide RNA designs for future studies. PMID:26165496

  4. Nurses' views of longitudinal genetic screening of and research on children.

    PubMed

    Gustafsson Stolt, Ulrica; Liss, Per-Erik; Ludvigsson, Johnny

    There is a lack of empirical data exploring ethical issues of genetic screening and longitudinal research involving children. Therefore, this pilot interview study explored the perceptions of nurses and midwives in relation to their involvement in an ongoing genetic preventive screening process involving children - the All Babies in South-east Sweden (ABIS) study (n=17,005). Data were collected through semistructured interviews with 10 nurses involved in all information and sampling procedures. While providing the preliminary nature of this study, it supports the idea of the importance of further research, both from a nursing professional perspective and from other parties involved in clinical research. The findings made in this study suggest that for such studies it is vital that nurses and midwives are fully informed about aims, methods, and potential intervention/prevention since in many cases they have a central role in several areas of screening and clinical longitudinal research involving children, e.g. information to potential research participants, obtaining informed consent, and data collection. With a thorough understanding of the research, including both basic aims and methods as well as potential future prevention aims, the nursing staff involved will be better placed to help participants make an informed choice and to provide additional information to the participants. Further research may be needed that aims to develop effective methods in preparing data collectors. It is also suggested that the design of the information process, and especially in longitudinal research involving young children, is of utmost importance before such studies are commenced.

  5. Genetic screens for Caenorhabditis elegans mutants defective in left/right asymmetric neuronal fate specification.

    PubMed

    Sarin, Sumeet; O'Meara, M Maggie; Flowers, Eileen B; Antonio, Celia; Poole, Richard J; Didiano, Dominic; Johnston, Robert J; Chang, Sarah; Narula, Surinder; Hobert, Oliver

    2007-08-01

    We describe here the results of genetic screens for Caenorhabditis elegans mutants in which a single neuronal fate decision is inappropriately executed. In wild-type animals, the two morphologically bilaterally symmetric gustatory neurons ASE left (ASEL) and ASE right (ASER) undergo a left/right asymmetric diversification in cell fate, manifested by the differential expression of a class of putative chemoreceptors and neuropeptides. Using single cell-specific gfp reporters and screening through a total of almost 120,000 haploid genomes, we isolated 161 mutants that define at least six different classes of mutant phenotypes in which ASEL/R fate is disrupted. Each mutant phenotypic class encompasses one to nine different complementation groups. Besides many alleles of 10 previously described genes, we have identified at least 16 novel "lsy" genes ("laterally symmetric"). Among mutations in known genes, we retrieved four alleles of the miRNA lsy-6 and a gain-of-function mutation in the 3'-UTR of a target of lsy-6, the cog-1 homeobox gene. Using newly found temperature-sensitive alleles of cog-1, we determined that a bistable feedback loop controlling ASEL vs. ASER fate, of which cog-1 is a component, is only transiently required to initiate but not to maintain ASEL and ASER fate. Taken together, our mutant screens identified a broad catalog of genes whose molecular characterization is expected to provide more insight into the complex genetic architecture of a left/right asymmetric neuronal cell fate decision.

  6. Dynamic visual acuity testing for screening patients with vestibular impairments.

    PubMed

    Peters, Brian T; Mulavara, Ajitkumar P; Cohen, Helen S; Sangi-Haghpeykar, Haleh; Bloomberg, Jacob J

    2012-01-01

    Dynamic visual acuity (DVA) may be a useful indicator of the function of the vestibulo-ocular reflex (VOR) but most DVA tests involve active head motion in the yaw plane. During gait the passive, vertical VOR may be more relevant and passive testing would be less likely to elicit compensatory strategies. The goal of this study was to determine if testing dynamic visual acuity during passive vertical motion of the subject would differentiate normal subjects from patients with known vestibular disorders. Subjects, normals and patients who had been diagnosed with either unilateral vestibular weaknesses or were post-acoustic neuroma resections, sat in a chair that could oscillate vertically with the head either free or constrained with a cervical orthosis. They viewed a computer screen 2 m away that showed Landholt C optotypes in one of 8 spatial configurations and which ranged in size from 0.4 to 1.0 logMAR. They were tested while the chair was stationary and while it was moving. Scores were worse for both groups during the dynamic condition compared to the static condition. In the dynamic condition patients' scores were significantly worse than normals' scores. Younger and older age groups differed slightly but significantly; the sample size was too small to examine age differences by decade. The data suggest that many well-compensated patients have dynamic visual acuity that is as good as age-matched normals. Results of ROC analyses were only moderate, indicating that the differences between patients and normals were not strong enough, under the conditions tested, for this test to be useful for screening people to determine if they have vestibular disorders. Modifications of the test paradigm may make it more useful for screening potential patients.

  7. Psychosocial effects in parents and children 12 years after newborn genetic screening for type 1 diabetes.

    PubMed

    Kerruish, Nicola J; Healey, Dione M; Gray, Andrew R

    2017-04-01

    Little is known about the psychosocial consequences of testing newborns for genetic susceptibility to multifactorial diseases. This study reports quantitative psychosocial evaluations of parents and children 12 years after screening for type 1 diabetes (T1D). Two parent-child cohorts participated: children at increased genetic risk of T1D and children at low genetic risk. T1D risk status was determined at birth as part of a prospective study investigating potential environmental triggers of autoimmunity. Parent measures included ratings of children's emotional, behavioural and social functioning (Child Behaviour Checklist) and parenting style (Alabama Parenting Questionnaire). Child self-concept was assessed using the self-description questionnaire (SDQ1). Statistical analyses were conducted to test for differences between the groups. Twelve years after testing there was no evidence that knowledge of a child's increased genetic risk of T1D adversely affected parental ratings of their child's emotional, behavioural or social functioning, or impacted upon parenting style. There was no adverse effect upon the child's assessment of their self-concept. This study provides important preliminary data concerning longer-term psychosocial effects of incorporating tests for genetic risk of complex disorders into NBS panels. While it is reassuring that no significant adverse effects have been detected, more data will be required to adequately inform policy.

  8. Changes in screening behaviors and attitudes toward screening from pre-test genetic counseling to post-disclosure in Lynch syndrome families.

    PubMed

    Burton-Chase, A M; Hovick, S R; Peterson, S K; Marani, S K; Vernon, S W; Amos, C I; Frazier, M L; Lynch, P M; Gritz, E R

    2013-03-01

    The purpose of this study was to examine colonoscopy adherence and attitudes toward colorectal cancer (CRC) screening in individuals who underwent Lynch syndrome genetic counseling and testing. We evaluated changes in colonoscopy adherence and CRC screening attitudes in 78 cancer-unaffected relatives of Lynch syndrome mutation carriers before pre-test genetic counseling (baseline) and at 6 and 12 months post-disclosure of test results (52 mutation negative and 26 mutation positive). While both groups were similar at baseline, at 12 months post-disclosure, a greater number of mutation-positive individuals had had a colonoscopy compared with mutation-negative individuals. From baseline to 12 months post-disclosure, the mutation-positive group demonstrated an increase in mean scores on measures of colonoscopy commitment, self-efficacy, and perceived benefits of CRC screening, and a decrease in mean scores for perceived barriers to CRC screening. Mean scores on colonoscopy commitment decreased from baseline to 6 months in the mutation-negative group. To conclude, adherence to risk-appropriate guidelines for CRC surveillance improved after genetic counseling and testing for Lynch syndrome. Mutation-positive individuals reported increasingly positive attitudes toward CRC screening after receiving genetic test results, potentially reinforcing longer term colonoscopy adherence.

  9. Exome sequencing is an efficient tool for genetic screening of Charcot-Marie-Tooth disease.

    PubMed

    Choi, Byung-Ok; Koo, Soo Kyung; Park, Mi-Hyun; Rhee, Hwanseok; Yang, Song-Ju; Choi, Kyoung-Gyu; Jung, Sung-Chul; Kim, Han Su; Hyun, Young Se; Nakhro, Khriezhanuo; Lee, Hye Jin; Woo, Hae-Mi; Chung, Ki Wha

    2012-11-01

    Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neuropathies and is a genetically and clinically heterogeneous disorder with variable inheritance modes. As several molecules have been reported to have therapeutic effects on CMT, depending on the underlying genetic causes, exact genetic diagnostics have become very important for executing personalized therapy. Whole-exome sequencing has recently been introduced as an available method to identify rare or novel genetic defects from genetic disorders. Particularly, CMT is a model disease to apply exome sequencing because more than 50 genes (loci) are involved in its development with weak genotype-phenotype correlation. This study performed the exome sequencing in 25 unrelated CMT patients who revealed neither 17p12 duplication/deletion nor several major CMT genes. This study identified eight causative heterozygous mutations (32%). This detection rate seems rather high because each sample was tested before the study for major genetic causes. Therefore, this study suggests that the exome sequencing can be a highly exact, rapid, and economical molecular diagnostic tool for CMT patients who are tested for major genetic causes.

  10. Screening of genetic variants in ADCYAP1R1, MME and 14q21 in a Swedish cluster headache cohort.

    PubMed

    Ran, Caroline; Fourier, Carmen; Michalska, Julia M; Steinberg, Anna; Sjöstrand, Christina; Waldenlind, Elisabet; Belin, Andrea Carmine

    2017-08-22

    We have genotyped a Swedish cluster headache case-control population for three genetic variants representing the most significant markers identified in a recently published genome wide association study on cluster headache. The genetic variants were two common polymorphisms; rs12668955 in ADCYAP1R1 (adenylate cyclase activating polypeptide 1 receptor type 1), rs1006417, an intergenic variant on chromosome 14q21 and one rare mutation, rs147564881, in MME (membrane metalloendopeptidase). We screened 542 cluster headache patients and 581 controls using TaqMan real-time PCR on a 7500 fast cycler, and pyrosequencing on a PSQ 96 System. Statistical analysis for genotype and allele association showed that neither of the two common variants, rs12668955 and rs1006417 were associated with cluster headache. The MME mutation was investigated with pyrosequencing in patients, of whom all were wild type. In conclusion rs12668955 and rs1006417 do not impact the risk of developing cluster headache in the Swedish population. Also, rs147564881 does not seem to be enriched within the Swedish cluster headache patient group.

  11. Genetic screening for autosomal recessive nonsyndromic mental retardation in an isolated population in Israel.

    PubMed

    Basel-Vanagaite, Lina; Taub, Ellen; Halpern, Gabrielle J; Drasinover, Valerie; Magal, Nurit; Davidov, Bella; Zlotogora, Joël; Shohat, Mordechai

    2007-02-01

    Nonsyndromic mental retardation (NSMR) is the diagnosis of exclusion in mentally retarded individuals without additional abnormalities. We have recently identified a protein-truncating mutation, G408fsX437, in the gene CC2D1A on chromosome 19p13.12 in nine consanguineous Israeli Arab families with severe autosomal recessive NSMR, and have developed a comprehensive prevention program among the at-risk population in the village. The subjects tested were healthy women who were invited to undergo the genetic screening test as a part of their routine pregnancy monitoring. One hundred and seventeen subjects reported a family history positive for mental retardation. We tested 524 pregnant or preconceptional women and found 47 carriers (approximately 1/11), whose spouses were then recommended to undergo testing. We identified eight carrier couples, who were given genetic counseling and offered prenatal diagnosis. Of all the marriages, 28.6% were consanguineous; 16.5% of the total were between first cousins. The high prevalence of the mutation can be explained both by the founder effect owing to the generally high consanguinity rate among the inhabitants of the village, and also because two families with excessive numbers of mentally retarded offspring were unacceptable as marriage partners by the rest of the families. This is the first example of the establishment of a large-scale genetic screening program for autosomal recessive NSMR, which was made possible owing to the high frequency of the specific causative mutation in this isolated population.

  12. Adenomatous polyposis families that screen APC mutation-negative by conventional methods are genetically heterogeneous.

    PubMed

    Renkonen, Elise T; Nieminen, Pekka; Abdel-Rahman, Wael M; Moisio, Anu-Liisa; Järvelä, Irma; Arte, Sirpa; Järvinen, Heikki J; Peltomäki, Päivi

    2005-08-20

    One third of families with classical adenomatous polyposis (FAP), and a majority of those with attenuated FAP (AFAP), remain APC mutation-negative by conventional methods. Our purpose was to clarify the genetic basis of polyposis and genotype-phenotype correlations in such families. We studied a cohort of 29 adenomatous polyposis families that had screened APC mutation-negative by the protein truncation test, heteroduplex analysis, and exon-specific sequencing. The APC gene was investigated for large genomic rearrangements by multiplex ligation-dependent probe amplification (MLPA), and for allelic mRNA expression by single nucleotide primer extension (SNuPE). The AXIN2 gene was screened for mutations by sequencing. Four families (14%) showed a constitutional deletion of the entire APC gene (three families) or a single exon (one family). Seven families (24%) revealed reduced or extinct mRNA expression from one APC allele in blood, accompanied by loss of heterozygosity in the APC region in six (75%) of eight tumors. In 15 families (52%), possible APC involvement could be neither confirmed nor excluded. Finally, as detailed elsewhere, three families (10%) had germline mutations in genes other than APC, AXIN2 in one family, and MYH in two families. "APC mutation-negative" FAP is genetically heterogeneous, and a combination of MLPA and SNuPE is able to link a considerable proportion (38%) to APC. Significant differences were observed in clinical manifestations between subgroups, emphasizing the importance of accurate genetic and clinical characterization for the proper management of such families.

  13. Screening for Pancreatic Cancer.

    PubMed

    Ngamruengphong, Saowanee; Canto, Marcia Irene

    2016-12-01

    Pancreatic cancer (PC) is a highly fatal disease that can only be cured by complete surgical resection. However, most patients with PC have unresectable disease at the time of diagnosis, highlighting the need to detect PC and its precursor lesions earlier in asymptomatic patients. Screening is not cost-effective for population-based screening of PC. Individuals with genetic risk factors for PC based on family history or known PC-associated genetic syndromes, however, can be a potential target for PC screening programs. This article provides an overview of the epidemiology and genetic background of familial PC and discusses diagnostic and management approaches.

  14. Mutation Screening of Multiple Genes in Spanish Patients with Autosomal Recessive Retinitis Pigmentosa by Targeted Resequencing

    PubMed Central

    González-del Pozo, María; Borrego, Salud; Barragán, Isabel; Pieras, Juan I.; Santoyo, Javier; Matamala, Nerea; Naranjo, Belén; Dopazo, Joaquín; Antiñolo, Guillermo

    2011-01-01

    Retinitis Pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterised ultimately by the loss of photoreceptor cells. RP is the leading cause of visual loss in individuals younger than 60 years, with a prevalence of about 1 in 4000. The molecular genetic diagnosis of autosomal recessive RP (arRP) is challenging due to the large genetic and clinical heterogeneity. Traditional methods for sequencing arRP genes are often laborious and not easily available and a screening technique that enables the rapid detection of the genetic cause would be very helpful in the clinical practice. The goal of this study was to develop and apply microarray-based resequencing technology capable of detecting both known and novel mutations on a single high-throughput platform. Hence, the coding regions and exon/intron boundaries of 16 arRP genes were resequenced using microarrays in 102 Spanish patients with clinical diagnosis of arRP. All the detected variations were confirmed by direct sequencing and potential pathogenicity was assessed by functional predictions and frequency in controls. For validation purposes 4 positive controls for variants consisting of previously identified changes were hybridized on the array. As a result of the screening, we detected 44 variants, of which 15 are very likely pathogenic detected in 14 arRP families (14%). Finally, the design of this array can easily be transformed in an equivalent diagnostic system based on targeted enrichment followed by next generation sequencing. PMID:22164218

  15. Adjusting the frequency of mammography screening on the basis of genetic risk: Attitudes among women in the UK.

    PubMed

    Meisel, Susanne F; Pashayan, Nora; Rahman, Belinda; Side, Lucy; Fraser, Lindsay; Gessler, Sue; Lanceley, Anne; Wardle, Jane

    2015-06-01

    To explore public attitudes towards modifying frequency of mammography screening based on genetic risk. Home-based interviews were carried out with a population-based sample of 942 women aged 18-74 years in the UK. Demographic characteristics and perceived breast cancer (BC) risk were examined as predictors of support for risk-stratified BC screening and of the acceptability of raised or lowered screening frequency based on genetic risk, using multivariate logistic regression. Over two-thirds of respondents (65.8%) supported the idea of varying screening frequency on the basis of genetic risk. The majority (85.4%) were willing to have more frequent breast screening if they were found to be at higher risk, but fewer (58.8%) were willing to have less frequent screening if at lower risk (t (956) = 15.6, p < 0.001). Ethnic minority status was associated with less acceptability of more frequent screening (OR = 0.40, 95% CI = 0.21-0.74), but there were no other significant demographic correlates. Higher perceived risk of BC was associated with greater acceptability of more frequent screening (OR = 1.71, 95%CI = 1.27-2.30). Women were positive about adjusting the frequency of mammography screening in line with personal genetic risk, but it will be important to develop effective communication materials to minimise resistance to reducing screening frequency for those at lower genetic risk. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Patients' Attitudes Towards Disclosure of Genetic Test Results to Family Members: The Impact of Patients' Sociodemographic Background and Counseling Experience.

    PubMed

    Gilbar, Roy; Shalev, Stavit; Spiegel, Ronen; Pras, Elon; Berkenstadt, Michal; Sagi, Michal; Ben-Yehuda, Adi; Mor, Pnina; Perry, Shlomit; Zaccai, Tzipora Falik; Borochowitz, Zvi; Barnoy, Sivia

    2016-04-01

    Many factors predict the intention to disclose genetic information to relatives. The article examines the impact of patients' socio-demographic factors on their intention to disclose genetic testing results to their relatives. Data were collected in eight genetic clinics in Israel. Patients were requested to fill in a questionnaire after counseling. A convenience sample of 564 participants who visited these clinics was collected for a response rate of 85 %. Of them, 282 participants came for susceptibility testing for hereditary cancers (cancer group), and 282 for genetic screening tests (prenatal group). In the cancer group, being secular and having more years of education correlated positively with the intention to disclose test results to relatives. In the prenatal group, being married and female correlated positively with the intention to disclose. In the cancer group, being religious and with less years of education correlated positively with the view that the clinician should deliver the results to the family. In the prenatal group, being male and unmarried correlated positively with this belief. In both groups, being of young age correlated with the perception that genetic information is private. Varied sociodemographic factors affect the intention to inform family members. Thus, knowing the social background of patients will shed light on people's attitudes to genetic information and will help clinicians provide effective counseling in discussions with patients about the implications of test results for relatives.

  17. A neuron-based screening platform for optimizing genetically-encoded calcium indicators.

    PubMed

    Wardill, Trevor J; Chen, Tsai-Wen; Schreiter, Eric R; Hasseman, Jeremy P; Tsegaye, Getahun; Fosque, Benjamin F; Behnam, Reza; Shields, Brenda C; Ramirez, Melissa; Kimmel, Bruce E; Kerr, Rex A; Jayaraman, Vivek; Looger, Loren L; Svoboda, Karel; Kim, Douglas S

    2013-01-01

    Fluorescent protein-based sensors for detecting neuronal activity have been developed largely based on non-neuronal screening systems. However, the dynamics of neuronal state variables (e.g., voltage, calcium, etc.) are typically very rapid compared to those of non-excitable cells. We developed an electrical stimulation and fluorescence imaging platform based on dissociated rat primary neuronal cultures. We describe its use in testing genetically-encoded calcium indicators (GECIs). Efficient neuronal GECI expression was achieved using lentiviruses containing a neuronal-selective gene promoter. Action potentials (APs) and thus neuronal calcium levels were quantitatively controlled by electrical field stimulation, and fluorescence images were recorded. Images were segmented to extract fluorescence signals corresponding to individual GECI-expressing neurons, which improved sensitivity over full-field measurements. We demonstrate the superiority of screening GECIs in neurons compared with solution measurements. Neuronal screening was useful for efficient identification of variants with both improved response kinetics and high signal amplitudes. This platform can be used to screen many types of sensors with cellular resolution under realistic conditions where neuronal state variables are in relevant ranges with respect to timing and amplitude.

  18. A Neuron-Based Screening Platform for Optimizing Genetically-Encoded Calcium Indicators

    PubMed Central

    Schreiter, Eric R.; Hasseman, Jeremy P.; Tsegaye, Getahun; Fosque, Benjamin F.; Behnam, Reza; Shields, Brenda C.; Ramirez, Melissa; Kimmel, Bruce E.; Kerr, Rex A.; Jayaraman, Vivek; Looger, Loren L.; Svoboda, Karel; Kim, Douglas S.

    2013-01-01

    Fluorescent protein-based sensors for detecting neuronal activity have been developed largely based on non-neuronal screening systems. However, the dynamics of neuronal state variables (e.g., voltage, calcium, etc.) are typically very rapid compared to those of non-excitable cells. We developed an electrical stimulation and fluorescence imaging platform based on dissociated rat primary neuronal cultures. We describe its use in testing genetically-encoded calcium indicators (GECIs). Efficient neuronal GECI expression was achieved using lentiviruses containing a neuronal-selective gene promoter. Action potentials (APs) and thus neuronal calcium levels were quantitatively controlled by electrical field stimulation, and fluorescence images were recorded. Images were segmented to extract fluorescence signals corresponding to individual GECI-expressing neurons, which improved sensitivity over full-field measurements. We demonstrate the superiority of screening GECIs in neurons compared with solution measurements. Neuronal screening was useful for efficient identification of variants with both improved response kinetics and high signal amplitudes. This platform can be used to screen many types of sensors with cellular resolution under realistic conditions where neuronal state variables are in relevant ranges with respect to timing and amplitude. PMID:24155972

  19. Dynamic visual acuity testing for screening patients with vestibular impairments

    PubMed Central

    Peters, Brian T.; Mulavara, Ajitkumar P.; Cohen, Helen S.; Sangi-Haghpeykar, Haleh; Bloomberg, Jacob J.

    2013-01-01

    Dynamic visual acuity (DVA) may be a useful indicator of the function of the vestibulo-ocular reflex (VOR) but most DVA tests involve active head motion in the yaw plane. During gait the passive, vertical VOR may be more relevant and passive testing would be less likely to elicit compensatory strategies. The goal of this study was to determine if testing dynamic visual acuity during passive vertical motion of the subject would differentiate normal subjects from patients with known vestibular disorders. Subjects, normals and patients who had been diagnosed with either unilateral vestibular weaknesses or were post-acoustic neuroma resections, sat in a chair that could oscillate vertically with the head either free or constrained with a cervical orthosis. They viewed a computer screen 2 m away that showed Landholt C optotypes in one of 8 spatial configurations and which ranged in size from 0.4 to 1.0 logMAR. They were tested while the chair was stationary and while it was moving. Scores were worse for both groups during the dynamic condition compared to the static condition. In the dynamic condition patients’ scores were significantly worse than normals’ scores. Younger and older age groups differed slightly but significantly; the sample size was too small to examine age differences by decade. The data suggest that many well-compensated patients have dynamic visual acuity that is as good as age-matched normals. Results of ROC analyses were only moderate, indicating that the differences between patients and normals were not strong enough, under the conditions tested, for this test to be useful for screening people to determine if they have vestibular disorders. Modifications of the test paradigm may make it more useful for screening potential patients. PMID:23000614

  20. Genetic screens and functional genomics using CRISPR/Cas9 technology.

    PubMed

    Hartenian, Ella; Doench, John G

    2015-04-01

    Functional genomics attempts to understand the genome by perturbing the flow of information from DNA to RNA to protein, in order to learn how gene dysfunction leads to disease. CRISPR/Cas9 technology is the newest tool in the geneticist's toolbox, allowing researchers to edit DNA with unprecedented ease, speed and accuracy, and representing a novel means to perform genome-wide genetic screens to discover gene function. In this review, we first summarize the discovery and characterization of CRISPR/Cas9, and then compare it to other genome engineering technologies. We discuss its initial use in screening applications, with a focus on optimizing on-target activity and minimizing off-target effects. Finally, we comment on future challenges and opportunities afforded by this technology.

  1. Genetic Screening for Bacterial Mutants in Liquid Growth Media By Fluorescence-Activated Cell Sorting

    PubMed Central

    Abuaita, Basel H.; Withey, Jeffrey H.

    2010-01-01

    Many bacterial pathogens have defined in vitro virulence inducing conditions in liquid media which lead to production of virulence factors important during an infection. Identifying mutants that no longer respond to virulence inducing conditions will increase our understanding of bacterial pathogenesis. However, traditional genetic screens require growth on solid media. Bacteria in a single colony are in every phase of the growth curve, which complicates the analysis and make screens for growth phase-specific mutants problematic. Here, we utilize fluorescence-activated cell sorting in conjunction with random transposon mutagenesis to isolate bacteria grown in liquid media that are defective in virulence activation. This method permits analysis of an entire bacterial population in real time and selection of individual bacterial mutants with the desired gene expression profile at any time point after induction. We have used this method to identify Vibrio cholerae mutants defective in virulence induction. PMID:21094189

  2. Tay-Sachs disease carrier screening: a model for prevention of genetic disease.

    PubMed

    Kaplan, F

    1998-01-01

    Tay-Sachs disease (TSD) is an autosomal-recessive, progressive, and ultimately fatal neurodegenerative disorder. Within the last 30 years, the discovery of the enzymatic basis of the disease, namely deficiency of the enzyme hexosaminidase A, made possible both enzymatic diagnosis of TSD and heterozygote identification. In the last decade, the cloning of the HEXA gene and the identification of more than 80 associated TSD-causing mutations has permitted molecular diagnosis in many instances. TSD was the first genetic condition for which community-based screening for carrier detection was implemented. As such, the TSD experience can be viewed as a prototypic effort for public education, carrier testing, and reproductive counseling for avoiding fatal childhood disease. More importantly, the outcome of TSD screening over the last 28 years offers convincing evidence that such an effort can dramatically reduce incidence of the disease.

  3. Screening for apraxia: a short assessment for stroke patients.

    PubMed

    Almeida, Quincy J; Black, Sandra E; Roy, Eric A

    2002-01-01

    Apraxia is a disorder that involves impaired ability to execute previously learned movements that cannot be attributed to basic sensory or motor disturbances. A thorough assessment of apraxia typically entails both pantomiming and imitation of transitive (tool-related), intransitive (communication-related), and meaningless gestures, presented in an array of different, process-dependent sensory conditions. Precise and detailed assessment tools are often time-consuming and a shorter screening tool may be desirable for efficient surveillance of this disorder in stroke patients. In the present study, stroke patients (N = 37) were compared to healthy controls (N = 30) in their production of commonly used transitive and intransitive gestures. Five gestures (knife, flipper, tweezers, okay sign, cab hailing) were consistently performed with poorer accuracy in stroke patients when compared to healthy controls. The combination of gestures that best captured apraxic performance was statistically determined based on Z-score data. Results provide a shortened and sensitive method of detecting apraxia in stroke patients.

  4. Patient-physician language concordance and primary care screening among spanish-speaking patients.

    PubMed

    Eamranond, Pracha Peter; Davis, Roger B; Phillips, Russell S; Wee, Christina C

    2011-07-01

    Language discordance between patient and physician is associated with worse patient self-reported healthcare quality. As Hispanic patients have low rates of cardiovascular and cancer screening, we sought to determine whether patient-physician language concordance was associated with differences in rates of screening. We performed a retrospective medical record review of 101 Spanish-speaking patients cared for by 6 Spanish-speaking PCPs (language-concordant group) and 205 Spanish-speaking patients cared for by 44 non-Spanish-speaking PCPs (language-discordant group). Patients were included in the study if they were of age 35 to 75 years and had used interpreter services 2001 to 2006 in 2 Boston-based primary care clinics. Our outcomes included screening for hyperlipidemia, diabetes, cervical cancer, breast cancer, and colorectal cancer with age-appropriate and sex-appropriate subgroups. Our main predictor of interest was patient-physician language concordance. In multivariable modeling, we adjusted for age, sex, insurance status, number of primary care visits, and comorbidities. We adjusted for clustering of patients within individual physicians and clinic sites using generalized estimating equations. Patients in the language-discordant group tended to be female compared with patients in the language-concordant group. There were no significant differences in age, insurance status, number of primary care visits, or Charlson comorbidity index between the 2 groups. Rates of screening for hyperlipidemia, diabetes, cervical cancer, and breast cancer were similar for both language-concordant and language-discordant groups. However, patients in the language-concordant group were less likely to be screened for colorectal cancer compared with the language-discordant group risk ratio 0.78 (95% confidence interval, 0.61-0.99) after multivariable adjustment. This study finds that Spanish-speaking patients cared for by language-concordant PCPs were not more likely to receive

  5. Screening of risk from patient manual handling with MAPO method.

    PubMed

    Battevi, Natale; Menoni, Olga

    2012-01-01

    International standards highlight the steps required by risk assessment and involving first hazard identification, then risk evaluation and finally, if necessary, risk assessment. To check approach appropriateness to "risk evaluation" from manual patient handling through MAPO, a cross study was carried out in view of checking relationship between this new risk assessment model and occurrence of acute low back pain. After proper training the MAPO screening method was assessed in 31 wards, 411 exposed subjects of geriatric hospitals. At the same time health data were collected on occurrence of low back pain episodes during the last year both in the exposed subjects' group and the external reference group (n�237). Risk and clinical assessment data were tutored and checked by EPM research unit. The logistic analysis was used as a method to evaluate the relationship between risk index and acute low back pain. Investigating relationship between acute low back pain episodes and levels of MAPO screening index, carried out only with the people exposed who claimed to work for at least 30 hours per week (n = 178), showed definitely positive trends. The study results indicate that MAPO screening may represent a useful tool to estimate the risk from manual handling patients.

  6. Patient Difficulty Using Tablet Computers to Screen in Primary Care

    PubMed Central

    Santucci, Aimee; McTigue, Kathleen; Fischer, Gary; Kapoor, Wishwa

    2008-01-01

    Background Patient-administered computerized questionnaires represent a novel tool to assist primary care physicians in the delivery of preventive health care. Objective The aim of this study was to assess patient-reported ease of use with a self-administered tablet computer-based questionnaire in routine clinical care. Design All patients seen in a university-based primary care practice were asked to provide routine screening information using a touch-screen tablet computer-based questionnaire. Patients reported difficulty using the tablet computer after completion of their first questionnaire. Patients Ten thousand nine hundred ninety-nine patients completed the questionnaire between January 2004 and January 2006. Measurements We calculated rates of reporting difficulty (no difficulty, some difficulty, or a lot of difficulty) using the tablet computers based on patient age, sex, race, educational attainment, marital status, and number of comorbid medical conditions. We constructed multivariable ordered logistic models to identify predictors of increased self-reported difficulty using the computer. Results The majority of patients (84%) reported no difficulty using the tablet computers to complete the questionnaire, with only 3% reporting a lot of difficulty. Significant predictors of reporting more difficulty included increasing age [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.05–1.05)]; Asian race (OR 2.3, 95% CI 1.8–2.9); African American race (OR 1.4, 95% CI 1.2–1.6); less than a high school education (OR 3.0, 95% CI 2.6–3.4); and the presence of comorbid medical conditions (1–2: OR 1.3, 95% CI 1.2–1.5; ≥3: OR 1.7 95% CI 1.5–2.1). Conclusions The majority of primary care patients reported no difficulty using a self-administered tablet computer-based questionnaire. While computerized questionnaires present opportunities to collect routine screening information from patients, attention must be paid to vulnerable groups. PMID:18373148

  7. Human Genetics in Rheumatoid Arthritis Guides a High-Throughput Drug Screen of the CD40 Signaling Pathway

    PubMed Central

    Li, Gang; Diogo, Dorothée; Wu, Di; Spoonamore, Jim; Dancik, Vlado; Franke, Lude; Kurreeman, Fina; Rossin, Elizabeth J.; Duclos, Grant; Hartland, Cathy; Zhou, Xuezhong; Li, Kejie; Liu, Jun; De Jager, Philip L.; Siminovitch, Katherine A.; Zhernakova, Alexandra; Raychaudhuri, Soumya; Bowes, John; Eyre, Steve; Padyukov, Leonid; Gregersen, Peter K.; Worthington, Jane; Gupta, Namrata; Clemons, Paul A.; Stahl, Eli; Tolliday, Nicola; Plenge, Robert M.

    2013-01-01

    Although genetic and non-genetic studies in mouse and human implicate the CD40 pathway in rheumatoid arthritis (RA), there are no approved drugs that inhibit CD40 signaling for clinical care in RA or any other disease. Here, we sought to understand the biological consequences of a CD40 risk variant in RA discovered by a previous genome-wide association study (GWAS) and to perform a high-throughput drug screen for modulators of CD40 signaling based on human genetic findings. First, we fine-map the CD40 risk locus in 7,222 seropositive RA patients and 15,870 controls, together with deep sequencing of CD40 coding exons in 500 RA cases and 650 controls, to identify a single SNP that explains the entire signal of association (rs4810485, P = 1.4×10−9). Second, we demonstrate that subjects homozygous for the RA risk allele have ∼33% more CD40 on the surface of primary human CD19+ B lymphocytes than subjects homozygous for the non-risk allele (P = 10−9), a finding corroborated by expression quantitative trait loci (eQTL) analysis in peripheral blood mononuclear cells from 1,469 healthy control individuals. Third, we use retroviral shRNA infection to perturb the amount of CD40 on the surface of a human B lymphocyte cell line (BL2) and observe a direct correlation between amount of CD40 protein and phosphorylation of RelA (p65), a subunit of the NF-κB transcription factor. Finally, we develop a high-throughput NF-κB luciferase reporter assay in BL2 cells activated with trimerized CD40 ligand (tCD40L) and conduct an HTS of 1,982 chemical compounds and FDA–approved drugs. After a series of counter-screens and testing in primary human CD19+ B cells, we identify 2 novel chemical inhibitors not previously implicated in inflammation or CD40-mediated NF-κB signaling. Our study demonstrates proof-of-concept that human genetics can be used to guide the development of phenotype-based, high-throughput small-molecule screens to identify potential novel therapies in

  8. Population genetic screening for alpha1-antitrypsin deficiency in a high-prevalence area.

    PubMed

    Corda, Luciano; Medicina, Daniela; La Piana, Giuseppe Emanuele; Bertella, Enrica; Moretti, Giovanni; Bianchi, Luca; Pinelli, Valentina; Savoldi, Gianfranco; Baiardi, Paola; Facchetti, Fabio; Gatta, Nuccia; Annesi-Maesano, Isabella; Balbi, Bruno

    2011-01-01

    Current guidelines for α1-antitrypsin deficiency (AATD) state that adult population screening should only be done in high-risk areas. Up-to-date genetic methods are always recommended. To determine the prevalence of AATD in a suspected high-risk area by population screening, applying new genetic analyses and comparing the prevalence of liver and lung abnormalities in subjects with or without AATD. Adult residents of Pezzaze, a village in an Italian alpine valley, voluntarily participated in the screening, and were examined for: nephelometric α1-antitrypsin (AAT) serum level, DNA analysis (mutagenic polymerase chain reaction and restriction fragment length polymorphism tests for Z and S AATD causative mutations, and denaturing high-performance liquid chromatography and/or direct gene sequencing if needed), serum aspartate and alanine transaminases, a respiratory questionnaire and the Medical Research Council dyspnea index scale. The prevalence of AATD was compared with that expected in Italy (Hardy-Weinberg equilibrium), and transaminases and the prevalence of respiratory symptoms were compared between study groups. Of 1,353 residents, 817 (60.4%) participated; 67 (8.2%) had low AAT serum levels (<90 mg/dl); 118 were carriers of AATD-associated alleles, 4 (0.5%) homozygotes or compound heterozygotes (1 Z, 1 S, 2 ZP(brescia)), 114 (14%) heterozygotes (46 Z, 52 S, 9 P(brescia), 4 M(wurzburg), 2 I, 1 P(lowell)). The prevalence and frequency of all AATD-related alleles was higher than expected for Italy (p < 0.001). There were no differences in symptoms of respiratory disease and transaminases between individuals with normal and low serum AAT. The screening design is one of the main strengths of this study. The large number of mostly asymptomatic individuals with AATD identified suggests that in high-risk areas adult population screening programs employing the latest genetic methods are feasible. Early recognition of individuals at risk means primary or secondary

  9. A Short History and Description of Drosophila melanogaster Classical Genetics: Chromosome Aberrations, Forward Genetic Screens, and the Nature of Mutations.

    PubMed

    Kaufman, Thomas C

    2017-06-01

    The purpose of this chapter in FlyBook is to acquaint the reader with the Drosophila genome and the ways in which it can be altered by mutation. Much of what follows will be familiar to the experienced Fly Pusher but hopefully will be useful to those just entering the field and are thus unfamiliar with the genome, the history of how it has been and can be altered, and the consequences of those alterations. I will begin with the structure, content, and organization of the genome, followed by the kinds of structural alterations (karyotypic aberrations), how they affect the behavior of chromosomes in meiotic cell division, and how that behavior can be used. Finally, screens for mutations as they have been performed will be discussed. There are several excellent sources of detailed information on Drosophila husbandry and screening that are recommended for those interested in further expanding their familiarity with Drosophila as a research tool and model organism. These are a book by Ralph Greenspan and a review article by John Roote and Andreas Prokop, which should be required reading for any new student entering a fly lab for the first time. Copyright © 2017 by the Genetics Society of America.

  10. Points to consider in designing a clinical trial to ascertain the utility of a genetic screening test.

    PubMed

    Rowley, P T; Loader, S

    2001-01-01

    In designing a clinical trial to ascertain the utility of a genetic screening test, the follow recommendations should be considered: (1) imbed the genetic test in a genetic service; (2) choose a specific outcome to monitor; (3) compare two strategies for achieving the desired outcome; (4) assemble a multidisciplinary team; (5) attempt to reach all potential subjects in a defined region; (6) derive an outcome for each subject; (7) assess each expected benefit and burden.

  11. The genetic basis of cardiac function: dissection by zebrafish (Danio rerio) screens.

    PubMed Central

    Warren, K S; Wu, J C; Pinet, F; Fishman, M C

    2000-01-01

    The vertebrate heart differs from chordate ancestors both structurally and functionally. Genetic units of form, termed 'modules', are identifiable by mutation, both in zebrafish and mouse, and correspond to features recently acquired in evolution, such as the ventricular chamber or endothelial lining of the vessels and heart. Zebrafish (Danio rerio) genetic screens have provided a reasonably inclusive set of such genes. Normal cardiac function may also be disrupted by single-gene mutations in zebrafish. Individual mutations may perturb contractility or rhythm generation. The zebrafish mutations which principally disturb cardiac contractility fall into two broad phenotypic categories, 'dilated' and 'hypertrophic'. Interestingly, these correspond to the two primary types of heart failure in humans. These disorders of early cardiac function provide candidate genes to be examined in complex human heart diseases, including arrhythmias and heart failure. PMID:11128987

  12. New Advances of Preimplantation and Prenatal Genetic Screening and Noninvasive Testing as a Potential Predictor of Health Status of Babies

    PubMed Central

    2014-01-01

    The current morphologically based selection of human embryos for transfer cannot detect chromosome aneuploidies. So far, only biopsy techniques have been able to screen for chromosomal aneuploidies in the in vitro fertilization (IVF) embryos. Preimplantation genetic diagnosis (PGD) or screening (PGS) involves the biopsy of oocyte polar bodies or embryonic cells and has become a routine clinical procedure in many IVF clinics worldwide, including recent development of comprehensive chromosome screening of all 23 pairs of chromosomes by microarrays for aneuploidy screening. The routine preimplantation and prenatal genetic diagnosis (PND) require testing in an aggressive manner. These procedures may be invasive to the growing embryo and fetus and potentially could compromise the clinical outcome. Therefore the aim of this review is to summarize not only the new knowledge on preimplantation and prenatal genetic diagnosis in humans, but also on the development of potential noninvasive embryo and fetal testing that might play an important role in the future. PMID:24783200

  13. New advances of preimplantation and prenatal genetic screening and noninvasive testing as a potential predictor of health status of babies.

    PubMed

    Milachich, Tanya

    2014-01-01

    The current morphologically based selection of human embryos for transfer cannot detect chromosome aneuploidies. So far, only biopsy techniques have been able to screen for chromosomal aneuploidies in the in vitro fertilization (IVF) embryos. Preimplantation genetic diagnosis (PGD) or screening (PGS) involves the biopsy of oocyte polar bodies or embryonic cells and has become a routine clinical procedure in many IVF clinics worldwide, including recent development of comprehensive chromosome screening of all 23 pairs of chromosomes by microarrays for aneuploidy screening. The routine preimplantation and prenatal genetic diagnosis (PND) require testing in an aggressive manner. These procedures may be invasive to the growing embryo and fetus and potentially could compromise the clinical outcome. Therefore the aim of this review is to summarize not only the new knowledge on preimplantation and prenatal genetic diagnosis in humans, but also on the development of potential noninvasive embryo and fetal testing that might play an important role in the future.

  14. Screening for Celiac disease in Hodgkin and non-Hodgkin lymphoma patients.

    PubMed

    Cil, Timuçin; Altintaş, Abdullah; Işikdoğan, Abdurrahman; Paşa, Semir; Bayan, Kadim; Batun, Sabri; Büyükbayram, Hüseyin

    2009-06-01

    Celiac disease is an abnormal T cell-mediated immune response against dietary gluten in genetically predisposed individuals. The aim of our prospective study was to evaluate the frequency of Celiac disease in patients with lymphoma and to determine the usefulness of the anti-gliadin and anti-endomysial antibodies (EMA) for diagnosis of Celiac disease in this patient group. We studied 119 patients with previously or newly diagnosed non-Hodgkin's lymphoma and 60 patients with Hodgkin's lymphoma who presented at the hematology and medical oncology divisions of Dicle University Hospital in Turkey between December 2002 and January 2006. Serological screening for Celiac disease was performed in all patients by searching for serum anti-gliadin immunoglobulin A and immunoglobulin G, and EMA immunoglobulin A and immunoglobulin G. In the Hodgkin's lymphoma group, anti-gliadin immunoglobulin A was detected in 9 (15%) patients (3 male, 6 female), and antigliadin immunoglobulin G was detected in 21 (35%) patients (15 male, 6 female). In the non-Hodgkin's lymphoma group, antigliadin immunoglobulin A was detected in 6 (5%) patients (2 M male 4 female), and anti-gliadin immunoglobulin G was detected in 30 (25.2%) patients (18 male, 12 female). EMA immunoglobulin A and immunoglobulin G were not detected in the Hodgkin's lymphoma and non-Hodgkin's lymphoma groups. Our report is the first to describe the frequency of Celiac disease in patients with lymphoma in the southeast region of Turkey. In our study, there was no evidence that Celiac disease is a pre-malignant condition for lymphoma. Serological screening for Celiac disease in lymphoma patients does not seem to be necessary.

  15. Genetic screening of non-classic CAH females with hyperandrogenemia identifies a novel CYP11B1 gene mutation.

    PubMed

    Shammas, Christos; Byrou, Stefania; Phelan, Marie M; Toumba, Meropi; Stylianou, Charilaos; Skordis, Nicos; Neocleous, Vassos; Phylactou, Leonidas A

    2016-04-01

    Congenital adrenal hyperplasia (CAH) is an endocrine autosomal recessive disorder with various symptoms of diverse severity. Mild hyperandrogenemia is the most commonclinical feature in non-classic CAH patients and 95% of the cases are identified by mutations in the CYP21A2 gene. In the present study, the second most common cause for non-classic CAH (NC-CAH), 11β-hydroxylase deficiency due to mutations in the CYP11B1 gene, is investigated. Screening of the CYP21A2 and CYP11B1 genes by direct sequencing was carried out for the detection of possible genetic defects in patients with suspected CAH. It wasobserved that CYP11B1 variants co-exist only in rare cases along with mutations in CYP21A2 in patients clinically diagnosed with CAH. A total of 23 NC-CAH female patients out of 75 were identified with only one mutation in the CYP21A2 gene. The novel CYP11B1 gene mutation, p.Val484Asp, was identified in a patient with CAH in the heterozygous state. The structural characterization of the novel p.Val484Asp was found to likely cause distortion of the surrounding beta sheet and indirect destabilization of the cavity that occurs on the opposite face of the structural elements, leading to partial impairment of the enzymatic activity. CYP21A2 gene mutations are the most frequent genetic defects in cases of NC-CAH even when these patients are in the heterozygous state. These mutations have a diverse phenotype giving rise to a variable extent of cortisol synthesis impairment; it is also clear that CYP11B1 mutants are a rare type of defects causing CAH.

  16. Screening for Suicide Ideation among Older Primary Care Patients

    PubMed Central

    Heisel, Marnin J.; Duberstein, Paul R.; Lyness, Jeffrey M.; Feldman, Mitchell D.

    2011-01-01

    Objectives Older adults have high rates of suicide and typically seek care in primary medical practices. Older adults often do not directly or spontaneously report thoughts of suicide, which can impede suicide prevention efforts. Therefore, the use of additional approaches to suicide risk detection is needed, including the use of screening tools. The objective of this study was to assess whether brief screens for depression have acceptable operating characteristics in identifying suicide ideation among older primary care patients and to examine potential sex differences in the screen’s accuracy. Methods We administered the 15-item Geriatric Depression Scale (GDS), which includes a 5-item GDS subscale (GDS-SI) designed to screen for suicide ideation, to a cross-sectional cohort of 626 primary care patients (235 men, 391 women) 65 years of age or older in the Northeastern United States. We assessed presence of suicide ideation with items from the Hamilton Rating Scale for Depression and the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Results Patients expressing suicide ideation (n = 69) scored higher on the GDS and GDS-SI than those who did not (n = 557). A GDS cut score of 4 maximized sensitivity (0.754) and specificity (0.815), producing an area under the curve of 0.844 (P < .001) and positive and negative predictive values of 0.335 and 0.964, respectively. Optimal cut scores were 5 for men and 3 for women. A GDS-SI cut score of 1 was optimal for the total sample and for both men and women. Conclusions The GDS and GDS-SI accurately identify older patients with suicide ideation. Research is needed to examine their acceptability and barriers to routine use in primary care. PMID:20207936

  17. Mutation screening of the PCDH15 gene in Spanish patients with Usher syndrome type I

    PubMed Central

    Jaijo, Teresa; Oshima, Aki; Aller, Elena; Carney, Carol; Usami, Shin-ichi; Kimberling, William J.

    2012-01-01

    Purpose PCDH15 codes for protocadherin-15, a cell-cell adhesion protein essential in the morphogenesis and cohesion of stereocilia bundles and in the function or preservation of photoreceptor cells. Mutations in the PCDH15 gene are responsible for Usher syndrome type I (USH1F) and non-syndromic hearing loss (DFNB23). The purpose of this work was to perform PCDH15 mutation screening to identify the genetic cause of the disease in a cohort of Spanish patients with Usher syndrome type I and establish phenotype-genotype correlation. Methods Mutation analysis of PCDH15 included additional exons recently identified and was performed by direct sequencing. The screening was performed in 19 probands with USH already screened for mutations in the most prevalent USH1 genes, myosin VIIA (MYO7A) and cadherin-23 (CDH23), and for copy number variants in PCDH15. Results Seven different point mutations, five novel, were detected. Including the large PCDH15 rearrangements previously reported in our cohort of patients, a total of seven of 19 patients (36.8%) were carriers of at least one pathogenic allele. Thirteen out of the 38 screened alleles carried pathogenic PCDH15 variants (34.2%). Conclusions Five out of the seven point mutations reported in the present study are novel, supporting the idea that most PCDH15 mutations are private. Furthermore, no mutational hotspots have been identified. In most patients, detected mutations led to a truncated protein, reinforcing the hypothesis that severe mutations cause the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment. PMID:22815625

  18. Biotinidase deficiency: clinical and genetic studies of 38 Brazilian patients.

    PubMed

    Borsatto, Taciane; Sperb-Ludwig, Fernanda; Pinto, Louise L C; Luca, Gisele R De; Carvalho, Francisca L; Souza, Carolina F M De; Medeiros, Paula F V De; Lourenço, Charles M; Lo Filho, Reinaldo; Neto, Eurico C; Bernardi, Pricila; Leistner-Segal, Sandra; Schwartz, Ida V

    2014-09-01

    Biotinidase deficiency (BD) is an inborn error of metabolism in which some genetic variants correlate with the level of enzyme activity. Biotinidase activity, however, may be artifactually low due to enzyme lability, premature birth, and jaundice; this hinders both phenotypic classification and the decision to implement therapy. This study sought to characterize the clinical and genetic profile of a sample of Brazilian patients exhibiting reduced biotinidase activity. This observational, multicenter study used a convenience sampling strategy, with sequencing of exons 2, 3, and 4 of the BTD gene. The sample comprised 38 individuals with biochemical phenotypes defined a priori on the basis of biotinidase activity in serum/plasma (2 with profound deficiency, 9 with partial deficiency, 15 heterozygous, 1 borderline between partial deficiency and heterozygosity, 2 borderline between heterozygous and normal) or dried blood spot sample (n = 9, all with unspecified deficiency). Most patients were from Southern Brazil (n = 29/38) and were identified by neonatal screening (n = 33/38). Parental consanguinity was reported in two cases. The most commonly found genetic variants were c.1330G > C (p.D444H), c.755A > G (p.D252G), and c.[511G > A;1330G > C] (p.[A171T;D444H]), with allele frequencies of 50%, 9.4%, and 5.4% respectively. Three novel pathogenic variants were identified (c.119 T > C or p.L40P, c.479G > A or p.C160Y, and c.664G > A or p.D222N). Twenty-nine patients had two pathogenic variants detected (with cis/trans status ascertained in 26/29), six had only one variant, and three had no pathogenic variants detected. Genotyping confirmed the original phenotypic classification based on enzyme activity in 16/26 cases. Three polymorphic variants were identified in control individuals, of which two were nonpathogenic (c.1171C > T or p.P391S and c.1413 T > C or p.C471C, with a frequency of 1.5% and 5.5% respectively) and one

  19. Biotinidase deficiency: clinical and genetic studies of 38 Brazilian patients

    PubMed Central

    2014-01-01

    Background Biotinidase deficiency (BD) is an inborn error of metabolism in which some genetic variants correlate with the level of enzyme activity. Biotinidase activity, however, may be artifactually low due to enzyme lability, premature birth, and jaundice; this hinders both phenotypic classification and the decision to implement therapy. This study sought to characterize the clinical and genetic profile of a sample of Brazilian patients exhibiting reduced biotinidase activity. Methods This observational, multicenter study used a convenience sampling strategy, with sequencing of exons 2, 3, and 4 of the BTD gene. Results The sample comprised 38 individuals with biochemical phenotypes defined a priori on the basis of biotinidase activity in serum/plasma (2 with profound deficiency, 9 with partial deficiency, 15 heterozygous, 1 borderline between partial deficiency and heterozygosity, 2 borderline between heterozygous and normal) or dried blood spot sample (n = 9, all with unspecified deficiency). Most patients were from Southern Brazil (n = 29/38) and were identified by neonatal screening (n = 33/38). Parental consanguinity was reported in two cases. The most commonly found genetic variants were c.1330G > C (p.D444H), c.755A > G (p.D252G), and c.[511G > A;1330G > C] (p.[A171T;D444H]), with allele frequencies of 50%, 9.4%, and 5.4% respectively. Three novel pathogenic variants were identified (c.119 T > C or p.L40P, c.479G > A or p.C160Y, and c.664G > A or p.D222N). Twenty-nine patients had two pathogenic variants detected (with cis/trans status ascertained in 26/29), six had only one variant, and three had no pathogenic variants detected. Genotyping confirmed the original phenotypic classification based on enzyme activity in 16/26 cases. Three polymorphic variants were identified in control individuals, of which two were nonpathogenic (c.1171C > T or p.P391S and c.1413 T > C or p.C471C, with a frequency of 1.5% and

  20. A genomewide screen for late-onset Alzheimer disease in a genetically isolated Dutch population.

    PubMed

    Liu, Fan; Arias-Vásquez, Alejandro; Sleegers, Kristel; Aulchenko, Yurii S; Kayser, Manfred; Sanchez-Juan, Pascual; Feng, Bing-Jian; Bertoli-Avella, Aida M; van Swieten, John; Axenovich, Tatiana I; Heutink, Peter; van Broeckhoven, Christine; Oostra, Ben A; van Duijn, Cornelia M

    2007-07-01

    Alzheimer disease (AD) is the most common cause of dementia. We conducted a genome screen of 103 patients with late-onset AD who were ascertained as part of the Genetic Research in Isolated Populations (GRIP) program that is conducted in a recently isolated population from the southwestern area of The Netherlands. All patients and their 170 closely related relatives were genotyped using 402 microsatellite markers. Extensive genealogy information was collected, which resulted in an extremely large and complex pedigree of 4,645 members. The pedigree was split into 35 subpedigrees, to reduce the computational burden of linkage analysis. Simulations aiming to evaluate the effect of pedigree splitting on false-positive probabilities showed that a LOD score of 3.64 corresponds to 5% genomewide type I error. Multipoint analysis revealed four significant and one suggestive linkage peaks. The strongest evidence of linkage was found for chromosome 1q21 (heterogeneity LOD [HLOD]=5.20 at marker D1S498). Approximately 30 cM upstream of this locus, we found another peak at 1q25 (HLOD=4.0 at marker D1S218). These two loci are in a previously established linkage region. We also confirmed the AD locus at 10q22-24 (HLOD=4.15 at marker D10S185). There was significant evidence of linkage of AD to chromosome 3q22-24 (HLOD=4.44 at marker D3S1569). For chromosome 11q24-25, there was suggestive evidence of linkage (HLOD=3.29 at marker D11S1320). We next tested for association between cognitive function and 4,173 single-nucleotide polymorphisms in the linked regions in an independent sample consisting of 197 individuals from the GRIP region. After adjusting for multiple testing, we were able to detect significant associations for cognitive function in four of five AD-linked regions, including the new region on chromosome 3q22-24 and regions 1q25, 10q22-24, and 11q25. With use of cognitive function as an endophenotype of AD, our study indicates the that the RGSL2, RALGPS2, and C1orf49 genes

  1. Genetic screening in a large family with juvenile onset primary open angle glaucoma

    PubMed Central

    Booth, A.; Anwar, R.; Chen, H.; Churchill, A.; Jay, J.; Polansky, J.; Nguyen, T.; Markham, A.

    2000-01-01

    AIMS—A number of genetic loci have been implicated in the pathogenesis of primary open angle glaucoma (POAG). The aim of this study was to identify the genetic cause of POAG in a large Scottish family and, if possible, offer genetic screening and advice to family members.
METHODS—Family members were examined to determine their disease status. Base excision sequence scanning was carried out in order to test for the presence of a POAG causing mutation at known genetic loci. Direct DNA sequencing was performed in order to determine the mutation sequence.
RESULTS—All family members of known affected disease status and two family members of unknown disease status were found to have a mutation in the TIGR gene. The mutation resulted in the substitution of a glycine residue with an arginine residue at codon 252 (Gly252Arg). No other sequence variations were present in any members of the family.
CONCLUSION—The Gly252Arg mutation in the TIGR gene results in the development of POAG in this family. It was possible to identify younger, currently unaffected, members of the family who carry the mutation and who are therefore at a very high risk of developing POAG themselves. This is the first demonstration that Gly252Arg can be a disease causing mutation rather than a benign polymorphism. The possible pathogenic mechanisms and wider implications of the mutation are considered.

 PMID:10873982

  2. Multimodality breast cancer screening in women with a familial or genetic predisposition

    PubMed Central

    Trop, I.; Lalonde, L.; Mayrand, M.H.; David, J.; Larouche, N.; Provencher, D.

    2010-01-01

    Background Women with a predisposition for breast cancer require a tailored screening program for early cancer detection. We evaluated the performance of mammography (mg), ultrasonography (us), and magnetic resonance imaging (mri) screening in these women. Patients and Methods In asymptomatic women either confirmed as BRCA1/2 carriers, or having a greater than 30% probability of being so as estimated by brcapro [Berry D, Parmigiani G. Duke spore (Specialized Program of Research Excellence) in Breast Cancer. 1999], we conducted a prospective comparative trial consisting of annual mri and mg, and biannual us and clinical breast examination. All evaluations were done within 30 days of one another. For each screening round, imaging tests were independently interpreted by three radiologists. Results The study enrolled 184 women, and 387 screening rounds were performed, detecting 12 cancers (9 infiltrating, 3 in situ), for an overall cancer yield of 6.5%. At diagnosis, 7 infiltrating cancers were smaller than 2 cm (T1); only 1 woman presented with axillary nodal metastases. All tumours were negative for the human epidermal growth factor receptor 2. Of the 12 cancers, mri detected 10, and mg, 7; us did not identify any additional cancers. The overall recall rate after mri was 21.8%, as compared with 11.4% for us and 16.1% for mg. Recall rates declined with successive screening rounds. In total, 45 biopsies were performed: 21 as a result of an us abnormality; 17, because of an mri lesion; and 7, because of a mg anomaly. Interpretation In high-risk women, mri offers the best sensitivity for breast cancer screening. The combination of yearly mri and mg reached a negative predictive value of 100%. The recall rate is greatest with mri, but declines for all modalities with successive screening rounds. PMID:20567624

  3. Validation and application of a novel integrated genetic screening method to a cohort of 1,112 men with idiopathic azoospermia or severe oligozoospermia.

    PubMed

    Oud, Manon S; Ramos, Liliana; O'Bryan, Moira K; McLachlan, Robert I; Okutman, Özlem; Viville, Stephane; de Vries, Petra F; Smeets, Dominique F C M; Lugtenberg, Dorien; Hehir-Kwa, Jayne Y; Gilissen, Christian; van de Vorst, Maartje; Vissers, Lisenka E L M; Hoischen, Alexander; Meijerink, Aukje M; Fleischer, Kathrin; Veltman, Joris A; Noordam, Michiel J

    2017-08-11

    Microdeletions of the Y chromosome (YCMs), Klinefelter syndrome (47,XXY), and CFTR mutations are known genetic causes of severe male infertility, but the majority of cases remain idiopathic. Here, we describe a novel method using single molecule Molecular Inversion Probes (smMIPs), to screen infertile men for mutations and copy number variations affecting known disease genes. We designed a set of 4,525 smMIPs targeting the coding regions of causal (n = 6) and candidate (n = 101) male infertility genes. After extensive validation, we screened 1,112 idiopathic infertile men with non-obstructive azoospermia or severe oligozoospermia. In addition to five chromosome YCMs and six other sex chromosomal anomalies, we identified five patients with rare recessive mutations in CFTR as well as a patient with a rare heterozygous frameshift mutation in SYCP3 that may be of clinical relevance. This results in a genetic diagnosis in 11-17 patients (1%-1.5%), a yield that may increase significantly when more genes are confidently linked to male infertility. In conclusion, we developed a flexible and scalable method to reliably detect genetic causes of male infertility. The assay consolidates the detection of different types of genetic variation while increasing the diagnostic yield and detection precision at the same or lower price compared with currently used methods. © 2017 Wiley Periodicals, Inc.

  4. Cancer Information Summaries: Screening/Detection

    MedlinePlus

    ... NCI Dictionaries NCI Dictionary of Cancer Terms NCI Drug Dictionary NCI Dictionary of Genetics Terms Blogs and Newsletters Health Communications Publications Reports PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer) Cancer Screening Overview (PDQ®) patient | ...

  5. Diabetes And Nutritional Screening In Post-Bariatric Patients.

    PubMed

    Pena, Maria E; Newaz, Trisha B

    2016-11-07

    With the rise of obesity there has been a concomitant increase in the incidence of type 2 diabetes (T2DM). As a result, the term "diabesity" has become a popular disease entity in the past several years. When lifestyle modification and pharmacotherapy fail to achieve successful weight loss and diabetes control, bariatric surgery is a recommended treatment option. Bariatric surgery has been shown to promote sustained T2DM remission in 30-63% of patients and improve other components of metabolic syndrome; thus a preferred term has been "metabolic surgery". As the practice of bariatric surgery for the treatment of T2DM increases, so will the number of patients with T2DM not achieving remission or with T2DM recurrence. There are currently no clear evidence-based guidelines delineating the proper management of T2DM in post-bariatric surgery patients. The focus of this review is to discuss current data on the efficacy of bariatric surgery in promoting T2DM remission, factors that predict T2DM remission and recurrence, and current treatment options for persistent hyperglycemia in post-bariatric surgery patients. To increase long-term T2DM remission and prevent or delay recurrence, post-bariatric surgery patients need close follow up to encourage adherence to healthy nutrition and lifestyle practices that will lead to sustained weight loss. In addition to this, patients need adequate nutritional supplementation and periodic screening for vitamin, mineral and protein deficiencies. Therefore, we will conclude with a brief review of current recommendations for nutritional deficiency screening and supplementation.

  6. Screening and Management of Delirium in Critically Ill Patients

    PubMed Central

    Farina, Nicholas; Smithburger, Pamela

    2015-01-01

    Delirium is highly prevalent in the critically ill population and has been associated with numerous negative outcomes including increased mortality. The presentation of a delirious patient in the intensive care unit (ICU) is characterized by a fluctuating cognitive status and inattention that varies dramatically among patients. Delirium can present in 3 different motoric subtypes: hyperactive, hypoactive, and mixed. Two tools, the Intensive Care Delirium Screening Checklist and Confusion Assessment ICU, are validated and recommended for the detection of delirium in critically ill patients. The identification of delirium in a critically ill patient should be facilitated using one of these tools. An intermediate form of delirium known as subsyndromal delirium also exists, although the significance of this syndrome is largely unknown. Another phenomenon known as sedation-related delirium has been recently described, although more research is needed to understand its significance. Patients in the ICU are exposed to many risk factors for developing delirium; controlling these risk factors is essential for preventing delirium development in critically ill patients. Nonpharmacologic interventions have been shown to prevent patients from developing delirium. Prevention is crucial because once delirium develops pharmacologic therapy is limited. PMID:26715799

  7. [Screening of early color vision loss in diabetic patients].

    PubMed

    Peduzzi, M; Longanesi, L; Ascari, A; Cascione, S; Galletti, M; Roncaia, R; Pacchioni, C; Maione, M

    1989-01-01

    Colour vision defects have been claimed to appear in diabetes before any retinopathy is visible. In the present study diabetic patients and non diabetic control subjects were screened with two different colour vision tests which include both red-green and blue-yellow parts, and are suitable for quantitative analysis of scores. The Lanthony 40 Hue test and the Tokyo Medical College--T.M.C. tables were used to assess colour vision in 106 diabetic (50 insulin dependent and 56 non insulin dependent) patients and in 99 non diabetic control subjects. Diabetic patients without visible retinopathy, familiar colour vision defects and/or lens changes, had significantly higher scores than control subjects in both eyes. The differences were more evident in non insulin dependent patients. Statistical analysis showed that early loss of colour vision was correlated with age and duration of diabetes for older patients, while correlation with glycosylated hemoglobin was moderately positive only for younger patients. Both tests (especially the Lanthony 40 Hue) resulted to be highly specific and could be used for the clinical study of colour vision losses in diabetic patients.

  8. Are diabetic patients being screened for sleep related breathing disorder?

    PubMed Central

    Surani, Salim

    2013-01-01

    Prevalence of both diabetes mellitus and obstructive sleep apnea (OSA) is high among general population. Both of these conditions are associated with significant morbidity. OSA affects approximately 25% of men and 9% of women, and its prevalence is even higher among obese, Hispanics, African American and diabetic patients. Diabetes on the other hand besides having high prevalence in general population has even higher prevalence among ethnic populations as Hispanics and African American. Despite the availability of several simple screening tools for OSA, as Berlin questionnaire, STOP-BANG questionnaire, NAMES Criteria, the utility for screening of OSA among the diabetic population remains marginal. This in turn can lead to significant morbidity and complications related to OSA as well as worsening of diabetes mellitus and increase in diabetic complications due to untreated sleep related breathing disorder. It is therefore imperative for the primary care giver to screen for OSA among the diabetic population as a part of their routine evaluation to prevent worsening of diabetes, and its cardiovascular, renal, ophthalmologic and neurological complications. PMID:24147199

  9. Genetic screening of wine-related enzymes in Lactobacillus species isolated from South African wines.

    PubMed

    Mtshali, P S; Divol, B; van Rensburg, P; du Toit, M

    2010-04-01

    The objective of this study was to investigate the presence of genes coding for enzymes of oenological relevance in wine Lactobacillus strains isolated from South African grape and wine samples during the 2001 and 2002 harvest seasons. A total of 120 wine lactobacilli isolates belonging to Lactobacillus plantarum, Lactobacillus hilgardii, Lactobacillus brevis, Lactobacillus pentosus, Lactobacillus paracasei, Lactobacillus sakei and Lactobacillus paraplantarum were genetically screened for enzyme-encoding genes using PCR with primers specific for beta-glucosidase, protease, esterase, citrate lyase and phenolic acid decarboxylase. The results of PCR screening showed that the Lactobacillus strains possessed different combinations of enzymes and that some strains did not possess any of the enzymes tested. Confirmation analysis with gene sequencing also showed high similarity of genes with those available in GenBank database. In this study, we have demonstrated the existence of genes coding for wine-related enzymes in wine lactobacilli that could potentially hydrolyse wine precursors to positively influence wine aroma. An expansion of knowledge on the genetic diversity of wine-associated lactic acid bacteria will enable the selection of novel malolactic fermentation starter cultures with desired oenological traits for the improvement of the organoleptic quality of the wine, and hence wine aroma.

  10. Aluminium tolerance in barley (Hordeum vulgare L.): physiological mechanisms, genetics and screening methods*

    PubMed Central

    Wang, Jun-ping; Raman, Harsh; Zhang, Guo-ping; Mendham, Neville; Zhou, Mei-xue

    2006-01-01

    Aluminium (Al) toxicity is one of the major limiting factors for barley production on acid soils. It inhibits root cell division and elongation, thus reducing water and nutrient uptake, consequently resulting in poor plant growth and yield. Plants tolerate Al either through external resistance mechanisms, by which Al is excluded from plant tissues or internal tolerance mechanisms, conferring the ability of plants to tolerate Al ion in the plant symplasm where Al that has permeated the plasmalemma is sequestered or converted into an innocuous form. Barley is considered to be most sensitive to Al toxicity among cereal species. Al tolerance in barley has been assessed by several methods, such as nutrient solution culture, soil bioassay and field screening. Genetic and molecular mapping research has shown that Al tolerance in barley is controlled by a single locus which is located on chromosome 4H. Molecular markers linked with Al tolerance loci have been identified and validated in a range of diverse populations. This paper reviews the (1) screening methods for evaluating Al tolerance, (2) genetics and (3) mechanisms underlying Al tolerance in barley. PMID:16972319

  11. A forward genetic screen reveals essential and non-essential RNAi factors in Paramecium tetraurelia

    PubMed Central

    Marker, Simone; Carradec, Quentin; Tanty, Véronique; Arnaiz, Olivier; Meyer, Eric

    2014-01-01

    In most eukaryotes, small RNA-mediated gene silencing pathways form complex interacting networks. In the ciliate Paramecium tetraurelia, at least two RNA interference (RNAi) mechanisms coexist, involving distinct but overlapping sets of protein factors and producing different types of short interfering RNAs (siRNAs). One is specifically triggered by high-copy transgenes, and the other by feeding cells with double-stranded RNA (dsRNA)-producing bacteria. In this study, we designed a forward genetic screen for mutants deficient in dsRNA-induced silencing, and a powerful method to identify the relevant mutations by whole-genome sequencing. We present a set of 47 mutant alleles for five genes, revealing two previously unknown RNAi factors: a novel Paramecium-specific protein (Pds1) and a Cid1-like nucleotidyl transferase. Analyses of allelic diversity distinguish non-essential and essential genes and suggest that the screen is saturated for non-essential, single-copy genes. We show that non-essential genes are specifically involved in dsRNA-induced RNAi while essential ones are also involved in transgene-induced RNAi. One of the latter, the RNA-dependent RNA polymerase RDR2, is further shown to be required for all known types of siRNAs, as well as for sexual reproduction. These results open the way for the dissection of the genetic complexity, interconnection, mechanisms and natural functions of RNAi pathways in P. tetraurelia. PMID:24860163

  12. Novel skin phenotypes revealed by a genome-wide mouse reverse genetic screen

    PubMed Central

    Liakath-Ali, Kifayathullah; Vancollie, Valerie E.; Heath, Emma; Smedley, Damian P.; Estabel, Jeanne; Sunter, David; DiTommaso, Tia; White, Jacqueline K.; Ramirez-Solis, Ramiro; Smyth, Ian; Steel, Karen P.; Watt, Fiona M.

    2014-01-01

    Permanent stop-and-shop large-scale mouse mutant resources provide an excellent platform to decipher tissue phenogenomics. Here we analyse skin from 538 knockout mouse mutants generated by the Sanger Institute Mouse Genetics Project. We optimize immunolabelling of tail epidermal wholemounts to allow systematic annotation of hair follicle, sebaceous gland and interfollicular epidermal abnormalities using ontology terms from the Mammalian Phenotype Ontology. Of the 50 mutants with an epidermal phenotype, 9 map to human genetic conditions with skin abnormalities. Some mutant genes are expressed in the skin, whereas others are not, indicating systemic effects. One phenotype is affected by diet and several are incompletely penetrant. In-depth analysis of three mutants, Krt76, Myo5a (a model of human Griscelli syndrome) and Mysm1, provides validation of the screen. Our study is the first large-scale genome-wide tissue phenotype screen from the International Knockout Mouse Consortium and provides an open access resource for the scientific community. PMID:24721909

  13. Parallel chemical genetic and genome-wide RNAi screens identify cytokinesis inhibitors and targets.

    PubMed

    Eggert, Ulrike S; Kiger, Amy A; Richter, Constance; Perlman, Zachary E; Perrimon, Norbert; Mitchison, Timothy J; Field, Christine M

    2004-12-01

    Cytokinesis involves temporally and spatially coordinated action of the cell cycle and cytoskeletal and membrane systems to achieve separation of daughter cells. To dissect cytokinesis mechanisms it would be useful to have a complete catalog of the proteins involved, and small molecule tools for specifically inhibiting them with tight temporal control. Finding active small molecules by cell-based screening entails the difficult step of identifying their targets. We performed parallel chemical genetic and genome-wide RNA interference screens in Drosophila cells, identifying 50 small molecule inhibitors of cytokinesis and 214 genes important for cytokinesis, including a new protein in the Aurora B pathway (Borr). By comparing small molecule and RNAi phenotypes, we identified a small molecule that inhibits the Aurora B kinase pathway. Our protein list provides a starting point for systematic dissection of cytokinesis, a direction that will be greatly facilitated by also having diverse small molecule inhibitors, which we have identified. Dissection of the Aurora B pathway, where we found a new gene and a specific small molecule inhibitor, should benefit particularly. Our study shows that parallel RNA interference and small molecule screening is a generally useful approach to identifying active small molecules and their target pathways.

  14. Parallel Chemical Genetic and Genome-Wide RNAi Screens Identify Cytokinesis Inhibitors and Targets

    PubMed Central

    Kiger, Amy A; Richter, Constance; Perlman, Zachary E; Perrimon, Norbert; Mitchison, Timothy J; Field, Christine M

    2004-01-01

    Cytokinesis involves temporally and spatially coordinated action of the cell cycle and cytoskeletal and membrane systems to achieve separation of daughter cells. To dissect cytokinesis mechanisms it would be useful to have a complete catalog of the proteins involved, and small molecule tools for specifically inhibiting them with tight temporal control. Finding active small molecules by cell-based screening entails the difficult step of identifying their targets. We performed parallel chemical genetic and genome-wide RNA interference screens in Drosophila cells, identifying 50 small molecule inhibitors of cytokinesis and 214 genes important for cytokinesis, including a new protein in the Aurora B pathway (Borr). By comparing small molecule and RNAi phenotypes, we identified a small molecule that inhibits the Aurora B kinase pathway. Our protein list provides a starting point for systematic dissection of cytokinesis, a direction that will be greatly facilitated by also having diverse small molecule inhibitors, which we have identified. Dissection of the Aurora B pathway, where we found a new gene and a specific small molecule inhibitor, should benefit particularly. Our study shows that parallel RNA interference and small molecule screening is a generally useful approach to identifying active small molecules and their target pathways. PMID:15547975

  15. New multiplex PCR methods for rapid screening of genetically modified organisms in foods.

    PubMed

    Datukishvili, Nelly; Kutateladze, Tamara; Gabriadze, Inga; Bitskinashvili, Kakha; Vishnepolsky, Boris

    2015-01-01

    We present novel multiplex PCR methods for rapid and reliable screening of genetically modified organisms (GMOs). New designed PCR primers targeting four frequently used GMO specific sequences permitted identification of new DNA markers, in particular 141 bp fragment of cauliflower mosaic virus (CaMV) 35S promoter, 224 bp fragment of Agrobacterium tumefaciens nopaline synthase (NOS) terminator, 256 bp fragment of 5-enolppyruvylshikimate-phosphate synthase (epsps) gene and 258 bp fragment of Cry1Ab delta-endotoxin (cry1Ab) gene for GMO screening. The certified reference materials containing Roundup Ready soybean (RRS) and maize MON 810 were applied for the development and optimization of uniplex and multiplex PCR systems. Evaluation of amplification products by agarose gel electrophoresis using negative and positive controls confirmed high specificity and sensitivity at 0.1% GMO for both RRS and MON 810. The fourplex PCR was developed and optimized that allows simultaneous detection of three common transgenic elements, such as: CaMV 35S promoter, NOS terminator, epsps gene together with soybean-specific lectin gene. The triplex PCR developed enables simultaneous identification of transgenic elements, such as: 35S promoter and cry1Ab gene together with maize zein gene. The analysis of different processed foods demonstrated that multiplex PCR methods developed in this study are useful for accurate and fast screening of GM food products.

  16. New multiplex PCR methods for rapid screening of genetically modified organisms in foods

    PubMed Central

    Datukishvili, Nelly; Kutateladze, Tamara; Gabriadze, Inga; Bitskinashvili, Kakha; Vishnepolsky, Boris

    2015-01-01

    We present novel multiplex PCR methods for rapid and reliable screening of genetically modified organisms (GMOs). New designed PCR primers targeting four frequently used GMO specific sequences permitted identification of new DNA markers, in particular 141 bp fragment of cauliflower mosaic virus (CaMV) 35S promoter, 224 bp fragment of Agrobacterium tumefaciens nopaline synthase (NOS) terminator, 256 bp fragment of 5-enolppyruvylshikimate-phosphate synthase (epsps) gene and 258 bp fragment of Cry1Ab delta-endotoxin (cry1Ab) gene for GMO screening. The certified reference materials containing Roundup Ready soybean (RRS) and maize MON 810 were applied for the development and optimization of uniplex and multiplex PCR systems. Evaluation of amplification products by agarose gel electrophoresis using negative and positive controls confirmed high specificity and sensitivity at 0.1% GMO for both RRS and MON 810. The fourplex PCR was developed and optimized that allows simultaneous detection of three common transgenic elements, such as: CaMV 35S promoter, NOS terminator, epsps gene together with soybean-specific lectin gene. The triplex PCR developed enables simultaneous identification of transgenic elements, such as: 35S promoter and cry1Ab gene together with maize zein gene. The analysis of different processed foods demonstrated that multiplex PCR methods developed in this study are useful for accurate and fast screening of GM food products. PMID:26257724

  17. Uncovering buffered pleiotropy: a genome-scale screen for mel-28 genetic interactors in Caenorhabditis elegans.

    PubMed

    Fernandez, Anita G; Mis, Emily K; Lai, Allison; Mauro, Michael; Quental, Angela; Bock, Carly; Piano, Fabio

    2014-01-10

    mel-28 (maternal-effect-lethal-28) encodes a conserved protein required for nuclear envelope function and chromosome segregation in Caenorhabditis elegans. Because mel-28 is a strict maternal-effect lethal gene, its function is required in the early embryo but appears to be dispensable for larval development. We wanted to test the idea that mel-28 has postembryonic roles that are buffered by the contributions of other genes. To find genes that act coordinately with mel-28, we did an RNA interference-based genetic interaction screen using mel-28 and wild-type larvae. We screened 18,364 clones and identified 65 genes that cause sterility in mel-28 but not wild-type worms. Some of these genes encode components of the nuclear pore. In addition we identified genes involved in dynein and dynactin function, vesicle transport, and cell-matrix attachments. By screening mel-28 larvae we have bypassed the requirement for mel-28 in the embryo, uncovering pleiotropic functions for mel-28 later in development that are normally provided by other genes. This work contributes toward revealing the gene networks that underlie cellular processes and reveals roles for a maternal-effect lethal gene later in development.

  18. Uncovering Buffered Pleiotropy: A Genome-Scale Screen for mel-28 Genetic Interactors in Caenorhabditis elegans

    PubMed Central

    Fernandez, Anita G.; Mis, Emily K.; Lai, Allison; Mauro, Michael; Quental, Angela; Bock, Carly; Piano, Fabio

    2013-01-01

    mel-28 (maternal-effect-lethal-28) encodes a conserved protein required for nuclear envelope function and chromosome segregation in Caenorhabditis elegans. Because mel-28 is a strict maternal-effect lethal gene, its function is required in the early embryo but appears to be dispensable for larval development. We wanted to test the idea that mel-28 has postembryonic roles that are buffered by the contributions of other genes. To find genes that act coordinately with mel-28, we did an RNA interference−based genetic interaction screen using mel-28 and wild-type larvae. We screened 18,364 clones and identified 65 genes that cause sterility in mel-28 but not wild-type worms. Some of these genes encode components of the nuclear pore. In addition we identified genes involved in dynein and dynactin function, vesicle transport, and cell-matrix attachments. By screening mel-28 larvae we have bypassed the requirement for mel-28 in the embryo, uncovering pleiotropic functions for mel-28 later in development that are normally provided by other genes. This work contributes toward revealing the gene networks that underlie cellular processes and reveals roles for a maternal-effect lethal gene later in development. PMID:24281427

  19. Child health providers' precautionary discussion of emotions during communication about results of newborn genetic screening.

    PubMed

    Farrell, Michael H; Speiser, Jodi; Deuster, Lindsay; Christopher, Stephanie

    2012-01-01

    To demonstrate a quantitative abstraction method for Communication Quality Assurance projects to assess physicians' communication about hidden emotions after newborn genetic screening. Communication quality indicator analysis. Standardized parent encounters performed in practicing physicians' clinics or during educational workshops for residents. Fifty-nine pediatrics residents, 53 pediatricians, and 31 family physicians. Participants were asked to counsel standardized parents about a screening result; counseling was recorded, transcribed, and parsed into statements (each with 1 subject and 1 predicate). Pairs of abstractors independently compared statements with a data dictionary containing explicit-criteria definitions. Four groups of "precautionary empathy" behaviors (assessment of emotion, anticipation/validation of emotion, instruction about emotion, and caution about future emotion), with definitions developed for both "definite" and "partial" instances. Only 38 of 143 transcripts (26.6%) met definite criteria for at least 1 of the precautionary empathy behaviors. When partial criteria were counted, this number increased to 80 of 143 transcripts (55.9%). The most common type of precautionary empathy was the "instruction about emotion" behavior (eg, "don't be worried"), which may sometimes be leading or premature. Precautionary empathy behaviors were rare in this analysis. Further study is needed, but this study should raise concerns about the quality of communication services after newborn screening.

  20. The Rising Incidence of Younger Patients With Colorectal Cancer: Questions About Screening, Biology, and Treatment.

    PubMed

    Connell, Louise C; Mota, José Mauricio; Braghiroli, Maria Ignez; Hoff, Paulo M

    2017-04-01

    Colorectal cancer (CRC) is the third leading cancer diagnosed globally and an important cause of cancer-related mortality. Of interest, while we have witnessed a declining incidence trend over the past few decades in the older population, incidence rates for adolescents and young adults have been increasing steadily. Several factors may well explain this apparent epidemic in the young, namely a lack of routine screening and emerging lifestyle issues such as obesity, lack of exercise, and dietary factors. It is known that both environmental and genetic factors can increase the likelihood of developing CRC. Although inherited susceptibility is associated with the most striking increases in risk, and must always be considered in a young patient with CRC, the majority of CRCs are in fact sporadic rather than familial. Early-onset CRC is a truly heterogeneous disease, with mounting evidence to suggest that this patient population has a distinctive molecular profile, very different to late-onset CRC cases. Currently, both younger and older patients with CRC are treated in essentially the same manner, but with a better understanding of the molecular mechanisms underlying CRC in the young, we will have the opportunity to specifically tailor screening and clinical management strategies in this unique patient population in an effort to improve outcomes. The aim of this review is to outline our current knowledge of the distinguishing features of early-onset CRC, the ongoing research efforts, and the evolving evidence in this field.

  1. [Nutritional risk screening and nutrition assessment for gastrointestinal cancer patients].

    PubMed

    Du, Yan-ping; Li, Ling-ling; He, Qing; Li, Yun; Song, Hu; Lin, Yi-jia; Peng, Jun-sheng

    2012-05-01

    To investigate the nutritional status, and provide evidence for nutritional treatment option. A total of 452 patients with gastrointestinal cancer were selected, including 156 gastric cancer,117 colon cancer, and 180 rectal cancer. The nutritional risk screening 2002(NRS2002) was applied to grade the nutritional risk. A multi-frequency bioelectrical impedance analysis was used to measure the patients' body composition. Albumin (Alb), prealbumin(PA), transferring(Tf), retinol binding protein(RBP), red blood cell(RBC), hemoglobin (Hb), haematocrit(Hct) were measured after fasting. The rate of patients with NRS2002 score more than 3 was 70.5%(110/156) for gastric cancer, 53.8%(63/117) for colon cancer, and 46.7%(86/180) for rectal cancer. The score for impaired nutritional status more than 1 for gastric cancer was higher than that for colorectal cancer(P<0.05), while patients with disease score more than 2 was less for gastric cancer(P<0.05). Body mass index(BMI), obesity degree, fat content, fat percentage, and arm circumference were lower in gastric cancer patients as compared to colorectal cancer patients(P<0.05); but protein percentage, muscle percentage, ratio of muscles of arm, and cell mass percentage were higher in gastric cancer patients(P<0.05). The proportions of patients with low Alb, PA, Tf, BC, Hb, Hct were higher for gastric cancer and colon cancer(P<0.05). Patients with gastric cancer are prone to fat loss and therefore have a higher nutritional risk and malnutrition than those with colorectal cancer. Combination of body composition analysis and laboratory examination may achieve comprehensive evaluation of the nutritional status of patients, and provide the evidence of nutritional therapy by being combined with NRS2002 score.

  2. Development of a forward genetic screen to isolate oil mutants in the green microalga Chlamydomonas reinhardtii

    PubMed Central

    2013-01-01

    Background Oils produced by microalgae are precursors to biodiesel. To achieve a profitable production of biodiesel from microalgae, identification of factors governing oil synthesis and turnover is desirable. The green microalga Chlamydomonas reinhardtii is amenable to genetic analyses and has recently emerged as a model to study oil metabolism. However, a detailed method to isolate various types of oil mutants that is adapted to Chlamydomonas has not been reported. Results We describe here a forward genetic approach to isolate mutants altered in oil synthesis and turnover from C. reinhardtii. It consists of a three-step screening procedure: a primary screen by flow cytometry of Nile red stained transformants grown in 96-deep-well plates under three sequential conditions (presence of nitrogen, then absence of nitrogen, followed by oil remobilization); a confirmation step using Nile red stained biological triplicates; and a validation step consisting of the quantification by thin layer chromatography of oil content of selected strains. Thirty-one mutants were isolated by screening 1,800 transformants generated by random insertional mutagenesis (1.7%). Five showed increased oil accumulation under the nitrogen-replete condition and 13 had altered oil content under nitrogen-depletion. All mutants were affected in oil remobilization. Conclusion This study demonstrates that various types of oil mutants can be isolated in Chlamydomonas based on the method set-up here, including mutants accumulating oil under optimal biomass growth. The strategy conceived and the protocol set-up should be applicable to other microalgal species such as Nannochloropsis and Chlorella, thus serving as a useful tool in Chlamydomonas oil research and algal biotechnology. PMID:24295516

  3. Enhanced hexose fermentation by Saccharomyces cerevisiae through integration of stoichiometric modeling and genetic screening.

    PubMed

    Quarterman, Josh; Kim, Soo Rin; Kim, Pan-Jun; Jin, Yong-Su

    2015-01-20

    In order to determine beneficial gene deletions for ethanol production by the yeast Saccharomyces cerevisiae, we performed an in silico gene deletion experiment based on a genome-scale metabolic model. Genes coding for two oxidative phosphorylation reactions (cytochrome c oxidase and ubiquinol cytochrome c reductase) were identified by the model-based simulation as potential deletion targets for enhancing ethanol production and maintaining acceptable overall growth rate in oxygen-limited conditions. Since the two target enzymes are composed of multiple subunits, we conducted a genetic screening study to evaluate the in silico results and compare the effect of deleting various portions of the respiratory enzyme complexes. Over two-thirds of the knockout mutants identified by the in silico study did exhibit experimental behavior in qualitative agreement with model predictions, but the exceptions illustrate the limitation of using a purely stoichiometric model-based approach. Furthermore, there was a substantial quantitative variation in phenotype among the various respiration-deficient mutants that were screened in this study, and three genes encoding respiratory enzyme subunits were identified as the best knockout targets for improving hexose fermentation in microaerobic conditions. Specifically, deletion of either COX9 or QCR9 resulted in higher ethanol production rates than the parental strain by 37% and 27%, respectively, with slight growth disadvantages. Also, deletion of QCR6 led to improved ethanol production rate by 24% with no growth disadvantage. The beneficial effects of these gene deletions were consistently demonstrated in different strain backgrounds and with four common hexoses. The combination of stoichiometric modeling and genetic screening using a systematic knockout collection was useful for narrowing a large set of gene targets and identifying targets of interest. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. A Differential Fluorescence-Based Genetic Screen Identifies Listeria monocytogenes Determinants Required for Intracellular Replication

    PubMed Central

    Perry, Kyle J.

    2013-01-01

    Listeria monocytogenes is a Gram-positive, facultative intracellular pathogen capable of causing severe invasive disease with high mortality rates in humans. While previous studies have largely elucidated the bacterial and host cell mechanisms necessary for invasion, vacuolar escape, and subsequent cell-to-cell spread, the L. monocytogenes factors required for rapid replication within the restrictive environment of the host cell cytosol are poorly understood. In this report, we describe a differential fluorescence-based genetic screen utilizing fluorescence-activated cell sorting (FACS) and high-throughput microscopy to identify L. monocytogenes mutants defective in optimal intracellular replication. Bacteria harboring deletions within the identified gene menD or pepP were defective for growth in primary murine macrophages and plaque formation in monolayers of L2 fibroblasts, thus validating the ability of the screening method to identify intracellular replication-defective mutants. Genetic complementation of the menD and pepP deletion strains rescued the in vitro intracellular infection defects. Furthermore, the menD deletion strain displayed a general extracellular replication defect that could be complemented by growth under anaerobic conditions, while the intracellular growth defect of this strain could be complemented by the addition of exogenous menaquinone. As prior studies have indicated the importance of aerobic metabolism for L. monocytogenes infection, these findings provide further evidence for the importance of menaquinone and aerobic metabolism for L. monocytogenes pathogenesis. Lastly, both the menD and pepP deletion strains were attenuated during in vivo infection of mice. These findings demonstrate that the differential fluorescence-based screening approach provides a powerful tool for the identification of intracellular replication determinants in multiple bacterial systems. PMID:23687268

  5. Genetic Screening of WNT4 and WNT5B in Two Populations with Deviating Bone Mineral Densities.

    PubMed

    Hendrickx, Gretl; Boudin, Eveline; Steenackers, Ellen; Nielsen, Torben Leo; Andersen, Marianne; Brixen, Kim; Van Hul, Wim

    2017-03-01

    A role for WNT4 and WNT5B in bone metabolism was indicated by genome-wide association studies (GWAS) and a Wnt4 knockout mouse model. The aim of this study was therefore to replicate and further investigate the causality between genetic variation in WNT4 and WNT5B and deviating bone mineral density (BMD) values. A WNT4 and WNT5B mutation screening was performed in patients with craniotubular hyperostosis using Sanger sequencing. Here, no putative causal mutations were detected. Moreover, a high and low BMD cohort was selected from the Odense Androgen Study population for re-sequencing. In WNT4 we detected four variants (three rare, one common), while in WNT5B we detected five variants (two rare, three common). For the common variants, no significant difference in genotype frequencies between the high and low BMD cohorts was observed. The SNPs associated with the GWAS were genotyped in these cohorts, but again no significant difference in genotype frequencies was observed. Despite the findings of the GWAS, we were not able to replicate or further verify the genetic association of polymorphisms in WNT4 and WNT5B with BMD. In order to do so, the intronic regions of both genes could be investigated more thoroughly in more extended populations (or extremes) with greater power. Future genetic and functional studies toward adjacent genes of WNT4 and WNT5B can also be interesting to figure out whether the signal from GWAS could possibly be attributed to genetic variation in these genes.

  6. Routine Screening for CYP2C19 Polymorphisms for Patients being Treated with Clopidogrel is not Recommended

    PubMed Central

    Hong, Robert A; Khan, Zia R; Valentin, Mona R; Badawi, Ramy A

    2015-01-01

    Recent efforts directed at potential litigation in Hawai‘i have resulted in a renewed interest for genetic screening for cytochrome P450 2C19 (CYP2C19) polymorphisms in patients treated with clopidogrel. Clopidogrel is an antiplatelet agent, frequently used in combination with aspirin, for the prevention of thrombotic complications with acute coronary syndrome and in patients undergoing percutaneous coronary interventions. Cytochrome P-450 (CYP) 2C19 is an enzyme involved in the bioactivation of clopidogrel from a pro-drug to an active inhibitor of platelet action. Patients of Asian and Pacific Island background have been reported to have an increase in CYP2C19 polymorphisms associated with loss-of-function of this enzyme when compared to other ethnicities. This has created an interest in genetic testing for CYP2C19 polymorphisms in Hawai‘i. Based upon our review of the current literature, we do not feel that there is support for the routine screening for CYP2C19 polymorphisms in patients being treated with clopidogrel; furthermore, the results of genetic testing may not be helpful in guiding therapeutic decisions. We recommend that decisions on the type of antiplatelet treatment be made based upon clinical evidence of potential differential outcomes associated with the use of these agents rather than on the basis of genetic testing. PMID:25628978

  7. A targeted approach to genetic counseling in breast cancer patients: the experience of an Italian local project.

    PubMed

    La Verde, Nicla; Corsi, Fabio; Moretti, Anna; Peissel, Bernard; Dalu, Davide; Girelli, Serena; Fasola, Cinzia; Gambaro, Anna; Roversi, Gaia; Azzollini, Jacopo; Radice, Paolo; Pensotti, Valeria; Farina, Gabriella; Manoukian, Siranoush

    2016-01-01

    Patients with hereditary breast cancer (BC) may benefit from genetic counseling and testing for detection of causative mutations, definition of therapeutic and preventive strategies, and identification of at-risk relatives. Italy has few oncogenetic centers and genetic evaluation of all patients with BC is not feasible. Moreover, lack of uniformity in the selection of patients generates inappropriate referral to the geneticist. We designed a model that may represent a reproducible way to select patients at risk for hereditary BC, with the aims of rationalizing access to genetic centers and improving clinical management and surveillance. The genetic unit of a Cancer Center and the Departments of Oncology from 2 public Hospitals in Milan were involved in the project. After training sessions at the genetic unit, operators from the 2 hospitals evaluated all patients with BC attending a first oncologic visit, through a specific interview. Patients considered at risk of hereditary BC attended counseling at the genetic unit. Of 419 patients, 61 (14.5%) were eligible for genetic counseling after the interview. Of these, 46 (10.9%) strictly met testing criteria. Overall, 52 (12.4%) patients underwent genetic counseling and 47 were tested for BRCA1/BRCA2 mutation. After genetic test results, the available options for treatment/surveillance were discussed by a multidisciplinary team, according to the level of genetic risk. It is possible to improve the process of referring patients with suspected hereditary BC for genetic risk assessment. The application of clinical screening reduced the genetics unit's workload and enabled optimization of time and resources.

  8. Assessment of the Readability of Genetic Counseling Patient Letters.

    PubMed

    Brown, Emily; Skinner, Megan; Ashley, Stephanie; Reed, Kate; Dixon, Shannan DeLany

    2016-06-01

    Patient letters are a powerful tool that genetic counselors use to communicate with their patients. Patient letters are often sent to provide information on a new diagnosis, reiterate test results, and to serve as a permanent record of the visit. Patient letters, however, are only helpful if the patients can understand them. More than 50 % of the US population reads below a 9th grade reading level and over one-third of the population has low health literacy skills. In this study we evaluate the readability of genetic counseling patient letters by assessing reading level, image use, and terminology use. One hundred forty-nine genetic counselors participated in the survey and of these, 79 submitted a sample patient letter. Analyses of the letters revealed a mean reading level of 10.93. On average, 6 genetic terms were included in each letter, and only 25 % of these terms were defined. Analyses of survey responses revealed over 75 % of the genetic counselors did not include images in their patient letters. These results indicate there is room for improvement in order to make genetic counseling patient letters more accessible to the general population.

  9. Preimplantation genetic diagnosis in patients with male meiotic abnormalities.

    PubMed

    Aran, B; Veiga, A; Vidal, F; Parriego, M; Vendrell, J M; Santaló, J; Egozcue, J; Barri, P N

    2004-04-01

    Indications and candidates for preimplantation genetic diagnosis (PGD) have increased in recent years. This study evaluates whether IVF-intracytoplasmic sperm injection (ICSI) results could be improved by selecting embryos through PGD-AS (aneuploidy screening) in couples in whom the male partner presents meiotic abnormalities. Two hundred and fifty-six embryos were biopsied and 183 were suitable for analysis (73.2%). Ninety-two embryos showed normal chromosomal analysis (50.3% of the analysed embryos and 57.5% of the diagnosed embryos). Pregnancy, abortion and implantation rates were compared with 66 IVF-ICSI cycles performed in 44 patients with meiotic abnormalities without PGD (control group). No statistically significant differences in the pregnancy rate (52 versus 43.9%), implantation rate (32.1 versus 23.5%) and miscarriage rate (15.4 versus 10.3%) were observed between the groups. Although the embryos obtained from men with meiotic abnormalities showed a high frequency of chromosome abnormalities, no improvements in pregnancy and implantation rates were obtained after PGD-AS in the series analysed.

  10. Screening for tuberculosis and LTBI in diabetes patients, Pohnpei, Federated States of Micronesia.

    PubMed

    Defang, R R; Brostrom, R; Ram, S; Johnson, E; Perman, P S

    2014-06-21

    A retrospective cohort study was performed in Pohnpei, a small Pacific Island, to evaluate the feasibility and results of screening adult diabetes (DM) patients for tuberculosis (TB) and latent tuberculous infection (LTBI) using a symptom screen, tuberculin skin testing and chest radiography. Of 79 patients, 65 (82%) completed screening. Two (3%) patients with active TB and 16 (25%) with LTBI were referred for anti-tuberculosis treatment and isoniazid preventive therapy, respectively. It is feasible and worthwhile to screen diabetes patients for TB, but a number of changes are needed to improve both the screening process and the diagnostic yield.

  11. Genetic basis of familial dilated cardiomyopathy patients undergoing heart transplantation.

    PubMed

    Cuenca, Sofia; Ruiz-Cano, Maria J; Gimeno-Blanes, Juan Ramón; Jurado, Alfonso; Salas, Clara; Gomez-Diaz, Iria; Padron-Barthe, Laura; Grillo, Jose Javier; Vilches, Carlos; Segovia, Javier; Pascual-Figal, Domingo; Lara-Pezzi, Enrique; Monserrat, Lorenzo; Alonso-Pulpon, Luis; Garcia-Pavia, Pablo

    2016-05-01

    Dilated cardiomyopathy (DCM) is the most frequent cause of heart transplantation (HTx). The genetic basis of DCM among patients undergoing HTx has been poorly characterized. We sought to determine the genetic basis of familial DCM HTx and to establish the yield of modern next generation sequencing (NGS) technologies in this setting. Fifty-two heart-transplanted patients due to familial DCM underwent NGS genetic evaluation with a panel of 126 genes related to cardiac conditions (59 associated with DCM). Genetic variants were initially classified as pathogenic mutations or as variants of uncertain significance (VUS). Final pathogenicity status was determined by familial cosegregation studies. Initially, 24 pathogenic mutations were found in 21 patients (40%); 25 patients (48%) carried 19 VUS and 6 (12%) did not show any genetic variant. Familial evaluation of 220 relatives from 36 of the 46 families with genetic variants confirmed pathogenicity in 14 patients and allowed reclassification of VUS as pathogenic in 17 patients, and as non-pathogenic in 3 cases. At the end of the study, the DCM-causing mutation was identified in 38 patients (73%) and 5 patients (10%) harbored only VUS. No genetic variants were identified in 9 cases (17%). The genetic spectrum of familial DCM patients undergoing HTx is heterogeneous and involves multiple genes. NGS technology plus detailed familial studies allow identification of causative mutations in the vast majority of familial DCM cases. Detailed familial studies remain critical to determine the pathogenicity of underlying genetic defects in a substantial number of cases. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  12. Functional Genetic Screen to Identify Interneurons Governing Behaviorally Distinct Aspects of Drosophila Larval Motor Programs.

    PubMed

    Clark, Matt Q; McCumsey, Stephanie J; Lopez-Darwin, Sereno; Heckscher, Ellie S; Doe, Chris Q

    2016-07-07

    Drosophila larval crawling is an attractive system to study rhythmic motor output at the level of animal behavior. Larval crawling consists of waves of muscle contractions generating forward or reverse locomotion. In addition, larvae undergo additional behaviors, including head casts, turning, and feeding. It is likely that some neurons (e.g., motor neurons) are used in all these behaviors, but the identity (or even existence) of neurons dedicated to specific aspects of behavior is unclear. To identify neurons that regulate specific aspects of larval locomotion, we performed a genetic screen to identify neurons that, when activated, could elicit distinct motor programs. We used 165 Janelia CRM-Gal4 lines-chosen for sparse neuronal expression-to ectopically express the warmth-inducible neuronal activator TrpA1, and screened for locomotor defects. The primary screen measured forward locomotion velocity, and we identified 63 lines that had locomotion velocities significantly slower than controls following TrpA1 activation (28°). A secondary screen was performed on these lines, revealing multiple discrete behavioral phenotypes, including slow forward locomotion, excessive reverse locomotion, excessive turning, excessive feeding, immobile, rigid paralysis, and delayed paralysis. While many of the Gal4 lines had motor, sensory, or muscle expression that may account for some or all of the phenotype, some lines showed specific expression in a sparse pattern of interneurons. Our results show that distinct motor programs utilize distinct subsets of interneurons, and provide an entry point for characterizing interneurons governing different elements of the larval motor program. Copyright © 2016 Clark et al.

  13. Functional Genetic Screen to Identify Interneurons Governing Behaviorally Distinct Aspects of Drosophila Larval Motor Programs

    PubMed Central

    Clark, Matt Q.; McCumsey, Stephanie J.; Lopez-Darwin, Sereno; Heckscher, Ellie S.; Doe, Chris Q.

    2016-01-01

    Drosophila larval crawling is an attractive system to study rhythmic motor output at the level of animal behavior. Larval crawling consists of waves of muscle contractions generating forward or reverse locomotion. In addition, larvae undergo additional behaviors, including head casts, turning, and feeding. It is likely that some neurons (e.g., motor neurons) are used in all these behaviors, but the identity (or even existence) of neurons dedicated to specific aspects of behavior is unclear. To identify neurons that regulate specific aspects of larval locomotion, we performed a genetic screen to identify neurons that, when activated, could elicit distinct motor programs. We used 165 Janelia CRM-Gal4 lines—chosen for sparse neuronal expression—to ectopically express the warmth-inducible neuronal activator TrpA1, and screened for locomotor defects. The primary screen measured forward locomotion velocity, and we identified 63 lines that had locomotion velocities significantly slower than controls following TrpA1 activation (28°). A secondary screen was performed on these lines, revealing multiple discrete behavioral phenotypes, including slow forward locomotion, excessive reverse locomotion, excessive turning, excessive feeding, immobile, rigid paralysis, and delayed paralysis. While many of the Gal4 lines had motor, sensory, or muscle expression that may account for some or all of the phenotype, some lines showed specific expression in a sparse pattern of interneurons. Our results show that distinct motor programs utilize distinct subsets of interneurons, and provide an entry point for characterizing interneurons governing different elements of the larval motor program. PMID:27172197

  14. A genetic strategy for combined screening and localized imaging of breast cancer

    PubMed Central

    Warram, Jason M.; Borovjagin, Anton V.; Zinn, Kurt R.

    2015-01-01

    PURPOSE Improvements are needed for the early detection of breast cancer, as current imaging methods lack sensitivity to detect small tumors and assess their disease phenotype. PROCEDURES To address this issue the dual reporter adenoviral vector (Ad5/3-Id1-SEAP-Id1-mCherry) was produced with a cancer specific Id1 promoter driving expression of a blood-based screening reporter (secreted embryonic alkaline phosphatase, SEAP) and a fluorescent imaging reporter (mCherry). This diagnostic system was assessed for its screening potential on breast cancer cell lines of various aggressive phenotypes. Reporter expression was measured and correlated with promoter level expression using western blot. Adenovirus receptor expression was normalized against reporter expression with luciferase infectivity assays. Ad5/3-Id1-SEAP-Id1-mCherry infected MDA-MB-231 cells combined with uninfected cells were implanted into the mammary fat pad of athymic nude mice to recapitulate low dose tumor delivery. Id1 driven SEAP expression and mCherry imaging were monitored to validate diagnostic sensitivity and efficacy. RESULTS Infected breast cancer cell lines displayed SEAP levels in the media that were 10-fold above background by 2 days after infection. Ad5/3-Id1-SEAP-Id1-mCherry infected cells (MOI=10) implanted in athymic nude mice demonstrated a 14-fold increase in serum SEAP levels over baseline when as little as 2.5% of the tumor contained infected cells. This robust response was also found for the mCherry reporter which was clearly visible in tumor xenografts on day 2 post implantation. CONCLUSIONS This diagnostic system that combines screening with imaging for early detection and monitoring of breast cancer can be easily extended to other reporters/modalities and cancer-targeting methods. Combining screening with imaging in a genetic, cancer-specific mechanism allows sensitive multi-modal detection and localization of breast cancer. PMID:20658194

  15. A genetic strategy for combined screening and localized imaging of breast cancer.

    PubMed

    Warram, Jason M; Borovjagin, Anton V; Zinn, Kurt R

    2011-06-01

    Improvements are needed for the early detection of breast cancer, as current imaging methods lack sensitivity to detect small tumors and assess their disease phenotype. To address this issue, the dual reporter adenoviral vector (Ad5/3-Id1-SEAP-Id1-mCherry) was produced with a cancer-specific Id1 promoter driving expression of a blood-based screening reporter (secreted embryonic alkaline phosphatase, SEAP) and a fluorescent imaging reporter (mCherry). This diagnostic system was assessed for its screening potential on breast cancer cell lines of various aggressive phenotypes. Reporter expression was measured and correlated with promoter level expression using Western blot. Adenovirus receptor expression was normalized against reporter expression with luciferase infectivity assays. Ad5/3-Id1-SEAP-Id1-mCherry infected MDA-MB-231 cells combined with uninfected cells were implanted into the mammary fat pad of athymic nude mice to recapitulate low-dose tumor delivery. Id1 driven SEAP expression and mCherry imaging were monitored to validate diagnostic sensitivity and efficacy. Infected breast cancer cell lines displayed SEAP levels in the media that were 10-fold above background by 2 days after infection. Ad5/3-Id1-SEAP-Id1-mCherry infected cells (multiplicity of infection = 10) implanted in athymic nude mice demonstrated a 14-fold increase in serum SEAP levels over baseline when as little as 2.5% of the tumor contained infected cells. This robust response was also found for the mCherry reporter, which was clearly visible in tumor xenografts on day 2 post implantation. This diagnostic system that combines screening with imaging for early detection and monitoring of breast cancer can be easily extended to other reporters/modalities and cancer-targeting methods. Combining screening with imaging in a genetic, cancer-specific mechanism allows sensitive multi-modal detection and localization of breast cancer.

  16. Genetic screening and evaluation for chromosomal abnormalities of infertile males in Jilin Province, China.

    PubMed

    Zhang, M; Fan, H-T; Zhang, Q-S; Wang, X-Y; Yang, X; Tian, W-J; Li, R-W

    2015-12-08

    Chromosomal abnormality is the most common genetic cause of male infertility, particularly in cases of azoospermia, oligozoospermia, and recurrent spontaneous abortion. Chromosomal rearrangement may interrupt an important gene or exert position effects. The functionality of genes at specific breakpoints, perhaps with a specific role in spermatogenesis, may be altered by such rearrangements. Structural chromosome abnormalities are furthermore known to increase the risk of pregnancy loss. In this study, we aimed to assess chromosomal defects in infertile men from Jilin Province, China, by genetic screening and to evaluate the relationship between structural chromosome abnormalities and male infertility. The prevalence of chromosomal abnormalities among the study participants (receiving genetic counseling in Jilin Province, China) was 10.55%. The most common chromosome abnormality was Klinefelter syndrome, and the study findings suggested that azoospermia and oligospermia may result from structural chromosomal abnormalities. Chromosome 1 was shown to be most commonly involved in male infertility and balanced chromosomal translocation was identified as one of the causes of recurrent spontaneous abortion. Chromosomes 4, 7, and 10 were the most commonly involved chromosomes in male partners of women experiencing repeated abortion.

  17. Application of SNPscan in Genetic Screening for Common Hearing Loss Genes

    PubMed Central

    Ke, Jia; Li, Tao; Hu, Ping; Song, Yu; Xu, Chiyu; Wang, Jie; Cheng, Jing; Zhang, Lei; Duan, Hong; Yuan, Huijun; Ma, Furong

    2016-01-01

    The current study reports the successful application of a fast and efficient genetic screening system for common hearing loss (HL) genes based on SNPscan genotyping technology. Genetic analysis of 115 variants in common genes related to HL, GJB2, SLC26A4 and MT-RNR, was performed on 695 subjects with non-syndromic hearing loss (NSHL) from the Northern China. The results found that 38.7% (269/695) of cases carried bi-allelic pathogenic variants in GJB2 and SLC26A4 and 0.7% (5/695) of cases carried homoplasmic MT-RNR1 variants. The variant allele frequency of GJB2, SLC26A4 and MT-RNR1 was 19.8% (275/1390), 21.9% (304/1390), and 0.86% (6/695), respectively. This approach can explain ~40% of NSHL cases and thus is a useful tool for establishing primary molecular diagnosis of NSHL in clinical genetics. PMID:27792752

  18. Low incidence of SCN1A genetic mutation in patients with hemiconvulsion-hemiplegia-epilepsy syndrome.

    PubMed

    Kim, Dong Wook; Lim, Byung Chan; Kim, Ki Joong; Chae, Jong Hee; Lee, Ran; Lee, Sang Kun

    2013-10-01

    Genetic mutations in SCN1A account for more than two-thirds of patients with classic Dravet syndrome. A role for SCN1A genetic mutations in the development of hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome was recently suggested based on the observation that HHE syndrome and classic Dravet syndrome share many clinical features. We previously identified a 2 bp-deletion mutation in SCN1A in a Dravet patient, and we found out the patient also had HHE syndrome upon clinical re-evaluation. We subsequently screened 10 additional HHE patients for SCN1A. Among the 11 patients who were diagnosed with HHE syndrome, six patients had no other etiology with the exception of prolonged febrile illness, therefore classified as idiopathic HHE syndrome, whereas five patients were classified as symptomatic HHE syndrome. Direct sequencing of all coding exons and flanking intronic sequences of the SCN1A gene was performed, but we failed to identify additional mutations in 10 patients. The patient with SCN1A mutation had the earliest onset of febrile convulsion and hemiparesis. Our study suggests that SCN1A genetic mutation is only a rare predisposing cause of HHE syndrome. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Using the gugging swallowing screen (GUSS) for dysphagia screening in acute stroke patients.

    PubMed

    John, Jennilee St; Berger, Linley

    2015-03-01

    Aspiration pneumonia from dysphagia following stroke presents significant morbidity and mortality in that population. Dysphagia screening before oral intake has been a standard of care for years, but there is a lack of consensus on the best screening tool. The Gugging Swallowing Screen (GUSS) is presented as a potentially better alternative to other dysphagia screens due to its safer progression of oral intake, more thorough evaluation of swallowing, and ability to enable earlier nutrition.

  20. Breast cancer genetic risk profile is differentially associated with interval and screen-detected breast cancers.

    PubMed

    Li, J; Holm, J; Bergh, J; Eriksson, M; Darabi, H; Lindström, L S; Törnberg, S; Hall, P; Czene, K

    2015-03-01

    Polygenic risk profiles computed from multiple common susceptibility alleles for breast cancer have been shown to identify women at different levels of breast cancer risk. We evaluated whether this genetic risk stratification can also be applied to discriminate between screen-detected and interval cancers, which are usually associated with clinicopathological and survival differences. A 77 single-nucleotide polymorphism polygenic risk score (PRS) was constructed for breast cancer overall and by estrogen receptor (ER) status. PRS was inspected as a continuous (per standard deviation increment) variable in a case-only design. Modification of the PRS by mammographic density was evaluated by fitting an additional interaction term. PRS weighted by breast cancer overall estimates was found to be differentially associated with 1865 screen-detected and 782 interval cancers in the LIBRO-1 study {age-adjusted odds ratio (OR)perSD [95% confidence interval (CI)] 0.91 [0.83-0.99], P = 0.023}. The association was found to be more significant for PRS weighted by ER-positive breast cancer estimates [ORperSD = 0.90 (0.82-0.98), P = 0.011]. This result was corroborated by two independent studies [combined ORperSD = 0.87 (0.76-1.00), P = 0.058] with no evidence of heterogeneity. When enriched for 'true' interval cancers among nondense breasts, the difference in the association with PRS in screen-detected and interval cancers became more pronounced [ORperSD = 0.74 (0.62-0.89), P = 0.001], with a significant interaction effect between PRS and mammographic density (Pinteraction = 0.017). To our knowledge, this is the first report looking into the genetic differences between screen-detected and interval cancers. It is an affirmation that the two types of breast cancer may have unique underlying biology. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  1. Screening of UBE3A gene in patients referred for Angelman Syndrome.

    PubMed

    Tzagkaraki, Evmorfia; Sofocleous, Christalena; Fryssira-Kanioura, Helen; Helen, Fryssira-Kanioura; Dinopoulos, Argyris; Goulielmos, Georgios; Mavrou, Ariadni; Kitsiou-Tzeli, Sofia; Sofia, Kitsiou-Tzeli; Kanavakis, Emmanuel

    2013-07-01

    Angelman Syndrome (AS) is a neurodevelopmental disorder characterized by severe developmental delay, speech impairment and unique behaviors including inappropriate laughter and happy disposition. AS is related to deficient maternal UBE3A gene expression caused either by chromosomal deletions, uniparental disomy, molecular defects of the imprinted 15q11-q13 critical region or by loss of function mutations in the maternally inherited UBE3A. In the present study, screening UBE3A was performed in 43 patients who were referred for AS but whom previous molecular diagnostic tests failed to provide a diagnosis. Two causative mutations--one of them novel--and four polymorphic variants one of which is also novel were revealed. Further investigation of 7 patients disclosed defects in other genes involved in clinical phenotypes mimicking AS. A typical EEG pattern and microcephaly in patients with developmental delay prompt for AS investigation while wide genetic screening should be applied to help resolution of the complex phenotypes characterized by developmental delay. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  2. Postoperative bleeding in a patient with normal screening coagulation tests.

    PubMed

    Nourbakhsh, Eva; Anvari, Reza; D'cunha, Nicholas; Thaxton, Lauren; Malik, Asim; Nugent, Kenneth

    2011-09-01

    A 54-year-old man was brought to the emergency room after a head-on collision. He had multiple fractures in his lower extremities and required immediate surgery. After surgery, the patient had a persistent drop in hemoglobin, hematocrit and platelets despite red blood cell transfusions. Laboratory studies included normal prothrombin time, activated partial thromboplastin time, normal plasminogen functional activity, negative antiplatelet antibodies, normal platelet functional analysis and negative disseminated intravascular coagulation screen. Factor XIII antigen levels were 25% of predicted, and the diagnosis of factor XIII deficiency was made. The patient was treated with cryoprecipitate, and the bleeding stopped. Patients with factor XIII deficiency have either a rare congenital or acquired coagulation disorder. Both presentations have normal standard laboratory clotting tests, and the diagnosis requires an assay measuring factor XIII activity or antigen levels. The usual treatment includes cryoprecipitate, fresh-frozen plasma or recombinant factor XIII. This deficiency should be considered in patients with unexplained spontaneous, traumatic or postoperative bleeding.

  3. Targeted genetic dependency screen facilitates identification of actionable mutations in FGFR4, MAP3K9, and PAK5 in lung cancer.

    PubMed

    Fawdar, Shameem; Trotter, Eleanor W; Li, Yaoyong; Stephenson, Natalie L; Hanke, Franziska; Marusiak, Anna A; Edwards, Zoe C; Ientile, Sara; Waszkowycz, Bohdan; Miller, Crispin J; Brognard, John

    2013-07-23

    Approximately 70% of patients with non-small-cell lung cancer present with late-stage disease and have limited treatment options, so there is a pressing need to develop efficacious targeted therapies for these patients. This remains a major challenge as the underlying genetic causes of ~50% of non-small-cell lung cancers remain unknown. Here we demonstrate that a targeted genetic dependency screen is an efficient approach to identify somatic cancer alterations that are functionally important. By using this approach, we have identified three kinases with gain-of-function mutations in lung cancer, namely FGFR4, MAP3K9, and PAK5. Mutations in these kinases are activating toward the ERK pathway, and targeted depletion of the mutated kinases inhibits proliferation, suppresses constitutive activation of downstream signaling pathways, and results in specific killing of the lung cancer cells. Genomic profiling of patients with lung cancer is ushering in an era of personalized medicine; however, lack of actionable mutations presents a significant hurdle. Our study indicates that targeted genetic dependency screens will be an effective strategy to elucidate somatic variants that are essential for lung cancer cell viability.

  4. [Cognitions and functioning in euthymic bipolar patients: screening and treatment].

    PubMed

    Bellivier, Frank

    2012-12-01

    Persistent cognitive deficits in euthymic bipolar patients are now well documented. Indeed, several studies and meta-analyzes clearly establish the existence of cognitive deficits in specific domains: attention (in particular sustained attention), Memory (in particular verbal memory) and executive functions. The impact of cognitive deficits on patient's functioning is also well documented and their role appear to be more important than expected by comparison with the impairment related to thymic residual symptoms. The development of specific cognitive remediation strategies is therefore a major hope for improving the quality of remission and functional outcome. The aetiology of these deficits remains poorly understood. However, the implication of factors related to the biological/genetic vulnerability to bipolar disorder is likely well as a "neurotoxic" effects of major mood episodes, in particular acute manic episodes that seems to play a important role in the worsening of these deficits over time. This further stresses the importance maintenance strategies for long-term functional outcome.

  5. Subgrouping Chronic Fatigue Syndrome Patients by Genetic and Immune Profiling

    DTIC Science & Technology

    2013-10-01

    Patients By Genetic And Immune Profiling PRINCIPAL INVESTIGATOR: Dr. Jose Montoya ...W81XWH-12-1-0388 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Dr. Jose Montoya , Ian Valencia, Holden Maecker, Michael Mindrinos

  6. Mutational screening of the RB1 gene in Italian patients with retinoblastoma reveals 11 novel mutations.

    PubMed

    Sampieri, Katia; Hadjistilianou, Theodora; Mari, Francesca; Speciale, Caterina; Mencarelli, Maria Antonietta; Cetta, Francesco; Manoukian, Siranoush; Peissel, Bernard; Giachino, Daniela; Pasini, Barbara; Acquaviva, Antonio; Caporossi, Aldo; Frezzotti, Renato; Renieri, Alessandra; Bruttini, Mirella

    2006-01-01

    Retinoblastoma (RB, OMIM#180200) is the most common intraocular tumour in infancy and early childhood. Constituent mutations in the RB1 gene predispose individuals to RB development. We performed a mutational screening of the RB1 gene in Italian patients affected by RB referred to the Medical Genetics of the University of Siena. In 35 unrelated patients, we identified germline RB1 mutations in 6 out of 9 familial cases (66%) and in 7 out of 26 with no family history of RB (27%). Using the single-strand conformational polymorphism (SSCP) technique, 11 novel mutations were detected, including 3 nonsense, 5 frameshift and 4 splice-site mutations. Only two of these mutations (1 splice site and 1 missense) were previously reported. The mutation spectrum reflects the published literature, encompassing predominately nonsense or frameshift and splicing mutations. RB1 germline mutation was detected in 37% of our cases. Gross rearrangements outside the investigated region, altered DNA methylation, or mutations in non-coding regions, may be the cause of disease in the remainder of the patients. Some cases, e.g. a case of incomplete penetrance, or variable expressivity ranging from retinoma to multiple tumours, are discussed in detail. In addition, a case of pre-conception genetic counselling resolved by rescue of banked cordonal blood of the affected deceased child is described.

  7. Identification of Autophagosome-associated Proteins and Regulators by Quantitative Proteomic Analysis and Genetic Screens*

    PubMed Central

    Dengjel, Jörn; Høyer-Hansen, Maria; Nielsen, Maria O.; Eisenberg, Tobias; Harder, Lea M.; Schandorff, Søren; Farkas, Thomas; Kirkegaard, Thomas; Becker, Andrea C.; Schroeder, Sabrina; Vanselow, Katja; Lundberg, Emma; Nielsen, Mogens M.; Kristensen, Anders R.; Akimov, Vyacheslav; Bunkenborg, Jakob; Madeo, Frank; Jäättelä, Marja; Andersen, Jens S.

    2012-01-01

    Autophagy is one of the major intracellular catabolic pathways, but little is known about the composition of autophagosomes. To study the associated proteins, we isolated autophagosomes from human breast cancer cells using two different biochemical methods and three stimulus types: amino acid deprivation or rapamycin or concanamycin A treatment. The autophagosome-associated proteins were dependent on stimulus, but a core set of proteins was stimulus-independent. Remarkably, proteasomal proteins were abundant among the stimulus-independent common autophagosome-associated proteins, and the activation of autophagy significantly decreased the cellular proteasome level and activity supporting interplay between the two degradation pathways. A screen of yeast strains defective in the orthologs of the human genes encoding for a common set of autophagosome-associated proteins revealed several regulators of autophagy, including subunits of the retromer complex. The combined spatiotemporal proteomic and genetic data sets presented here provide a basis for further characterization of autophagosome biogenesis and cargo selection. PMID:22311637

  8. Sleeping Beauty mutagenesis: exploiting forward genetic screens for cancer gene discovery.

    PubMed

    Mann, Michael B; Jenkins, Nancy A; Copeland, Neal G; Mann, Karen M

    2014-02-01

    Sleeping Beauty (SB) is a powerful insertional mutagen used in somatic forward genetic screens to identify novel candidate cancer genes. In the past two years, SB has become widely adopted to model human pancreatic, hepatocellular, colorectal and neurological cancers to identify loci that participate in tumor initiation, progression and metastasis. Oncogenomic approaches have directly linked hundreds of genes identified by SB with human cancers, many with prognostic implications. These SB candidate cancer genes are aiding to prioritize punitive human cancer genes for follow-up studies and as possible biomarkers or therapeutic targets. This review highlights recent advances in SB cancer gene discovery, approaches to validate candidate cancer genes, and efforts to integrate SB data across all tumor types to prioritize drug development and tumor specificity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Designer babies on tap? Medical students' attitudes to pre-implantation genetic screening.

    PubMed

    Meisenberg, Gerhard

    2009-03-01

    This paper describes two studies about the determinants of attitudes to pre-implantation genetic screening in a multicultural sample of medical students from the United States. Sample sizes were 292 in study 1 and 1464 in study 2. Attitudes were of an undifferentiated nature, but respondents did make a major distinction between use for disease prevention and use for enhancement. No strong distinctions were made between embryo selection and germ line gene manipulations, and between somatic gene therapy and germ line gene manipulations. Religiosity was negatively associated with acceptance of "designer baby" technology for Christians and Muslims but not Hindus. However, the strongest and most consistent influence was an apparently moralistic stance against active and aggressive interference with natural processes in general. Trust in individuals and institutions was unrelated to acceptance of the technology, indicating that fear of abuse by irresponsible individuals and corporations is not an important determinant of opposition.

  10. Subgrouping Chronic Fatigue Syndrome Patients by Genetic and Immune Profiling

    DTIC Science & Technology

    2014-10-01

    AWARD NUMBER: W81XWH-12-1-0388 TITLE: Subgrouping Chronic Fatigue Syndrome Patients by Genetic and Immune Profiling...2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Subgrouping Chronic Fatigue Syndrome Patients By Genetic And Immune Profiling 5b. GRANT...at the HLA level that makes you more susceptible to have Chronic Fatigue Syndrome (CFS) or any differences between the cases and controls. In order

  11. A forward genetic screen reveals essential and non-essential RNAi factors in Paramecium tetraurelia.

    PubMed

    Marker, Simone; Carradec, Quentin; Tanty, Véronique; Arnaiz, Olivier; Meyer, Eric

    2014-06-01

    In most eukaryotes, small RNA-mediated gene silencing pathways form complex interacting networks. In the ciliate Paramecium tetraurelia, at least two RNA interference (RNAi) mechanisms coexist, involving distinct but overlapping sets of protein factors and producing different types of short interfering RNAs (siRNAs). One is specifically triggered by high-copy transgenes, and the other by feeding cells with double-stranded RNA (dsRNA)-producing bacteria. In this study, we designed a forward genetic screen for mutants deficient in dsRNA-induced silencing, and a powerful method to identify the relevant mutations by whole-genome sequencing. We present a set of 47 mutant alleles for five genes, revealing two previously unknown RNAi factors: a novel Paramecium-specific protein (Pds1) and a Cid1-like nucleotidyl transferase. Analyses of allelic diversity distinguish non-essential and essential genes and suggest that the screen is saturated for non-essential, single-copy genes. We show that non-essential genes are specifically involved in dsRNA-induced RNAi while essential ones are also involved in transgene-induced RNAi. One of the latter, the RNA-dependent RNA polymerase RDR2, is further shown to be required for all known types of siRNAs, as well as for sexual reproduction. These results open the way for the dissection of the genetic complexity, interconnection, mechanisms and natural functions of RNAi pathways in P. tetraurelia. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. A Genetic Screen for Sleep and Circadian Mutants Reveals Mechanisms Underlying Regulation of Sleep in Drosophila

    PubMed Central

    Wu, Mark N.; Koh, Kyunghee; Yue, Zhifeng; Joiner, William J.; Sehgal, Amita

    2008-01-01

    Study Objectives: In order to characterize the genetic mechanisms underlying sleep, we have carried out a large-scale screen in Drosophila to identify short-sleeping mutants. The objectives of this study were as follows: (1) characterize the phenotypes of the shortest-sleeping mutants; (2) examine whether changes in arousal threshold or sleep homeostasis underlie short-sleeping phenotypes; (3) clone a gene affected in one of the shortest sleepers; and (4) investigate whether circadian mutants can be identified using light:dark (L:D) locomotor data obtained for studying sleep behavior. Design: Locomotor activity was measured using the Drosophila Activity Monitoring System in a 12:12 L:D cycle. Setting: Drosophila research laboratory. Participants: Adult flies from the 2nd chromosome Zuker collection, which contain mutations in most of the nonessential genes on the Drosophila 2nd chromosome. Measurements and Results: Our analysis of sleep characteristics suggests that daily activity (but not waking activity) correlates with daily sleep time and that defects in sleep maintenance are more common than defects in sleep initiation. Our shortest sleepers have intact or increased sleep rebound following sleep deprivation but show reduced thresholds for arousal. Molecular analysis of one of the short-sleeping lines indicates that it is a novel allele of a dopamine transporter (DAT). Finally, we describe a novel approach for identifying circadian mutants using L:D data. Conclusions: Our data suggest that most short-sleeping mutant phenotypes in Drosophila are characterized by an inability to stay asleep, most likely because of a reduced arousal threshold. Citation: Wu MN; Koh K; Yue Z; Joiner WJ; Sehgal A. A genetic screen for sleep and circadian mutants reveals mechanisms underlying regulation of sleep in Drosophila. SLEEP 2008;31(4):465-472. PMID:18457233

  13. Routine screening for suicidal intention in patients with cancer.

    PubMed

    Leung, Yvonne W; Li, Madeline; Devins, Gerald; Zimmermann, Camilla; Rydall, Anne; Lo, Chris; Rodin, Gary

    2013-11-01

    Suicide rates are elevated in individuals with cancer, although suicidal intention is not typically assessed in cancer centers. We evaluated in a large comprehensive cancer center the utility of an electronic Distress Assessment and Response Tool (DART), in which suicidal intention is assessed with a single item. Patients attending cancer clinics completed DART as part of routine care. DART includes measures of physical symptoms, depression, anxiety, social difficulties, and practical concerns. Medical variables were obtained from the Princess Margaret Cancer Registry, the data warehouse of cancer patient statistics. A Generalized Estimating Equation (GEE) model was used to assess factors associated with suicidal intention. Between September 2009 and March 2012, 4822/5461 patients (88.3%) who completed DART consented to the use of their data for research. Amongst the latter, 280 (5.9%) of the 4775 patients who answered the question reported suicidal ideation, which was related to physical and psychological distress, and social difficulties (ps < 0.0001). Amongst those with ideation who responded to the intention question, 20/186 (10.8%) reported suicidal intention. Of respondents with more severe suicidal ideation, 12/49 (24.5%) reported suicidal intention. Using a GEE model, suicidal intention in those with ideation was significantly associated with male sex, difficulty making treatment decisions, and with everyday living concerns. Suicidal ideation is reported on an electronic distress screening tool (DART) by almost 6% of cancer patients, of whom almost 11% report suicidal intention and 33% decline to indicate intention. DART demonstrated utility in identifying patients who may be at highest risk of completed suicide and who require urgent clinical assessment. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Importance of early nutritional screening in patients with gastric cancer.

    PubMed

    Gavazzi, Cecilia; Colatruglio, Silvia; Sironi, Alessandro; Mazzaferro, Vincenzo; Miceli, Rosalba

    2011-12-01

    In the present study, we evaluated the relationship between nutritional status, disease stage and quality of life (QoL) in 100 patients recently diagnosed with gastric carcinoma. The patients' nutritional status was investigated with anthropometric, biochemical, inflammatory and functional variables; and we also evaluated the nutritional risk with the Nutritional Risk Screening 2002. Oncological staging was standard. QoL was evaluated using the Functional Assessment of Anorexia/Cachexia Therapy questionnaire. The statistical correlation between nutritional risk score (NRS) and oncological characteristics or QoL was evaluated using both univariable and multivariable analyses. Weight loss and reduction of food intake were the most frequent pathological nutritional indicators, while biochemical, inflammatory and functional variables were in the normal range. According to NRS, thirty-six patients were malnourished or at risk for malnutrition. Patients with NRS ≥ 3 presented a significantly greater percentage of stage IV gastric cancer and pathological values of C-reactive protein, while no correlation was found with the site of tumour. NRS was negatively associated with QoL (P < 0·001) and this relation was independent from oncological and inflammatory variables as confirmed by multivariable analysis. In the present study, we found that in patients with gastric cancer malnutrition is frequent at diagnosis and this is likely due to reduction in food intake. Moreover, NRS is directly correlated with tumour stage and inversely correlated with QoL, which makes it a useful tool to identify patients in need of an early nutritional intervention during oncological treatments.

  15. Novel Heterozygous Genetic Variants in Patients with 46,XY Gonadal Dysgenesis.

    PubMed

    Chauhan, Vasundhera; Jyotsna, Viveka P; Jain, Vandana; Khadgawat, Rajesh; Dada, Rima

    2017-01-01

    46,XY gonadal dysgenesis (GD) constitutes a rare group of disorders characterized by the presence of dysfunctional testes in genotypic males. The molecular etiology is not known in about 2 thirds of instances. The aim of this study was to identify the genetic cause in patients with 46,XY gonadal dysgenesis. Based on clinical, cytogenetic, and biochemical screening, 10 patients with 46,XY GD were recruited. Direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes was carried out for molecular analysis. Among 10 patients, 5 were diagnosed with complete gonadal dysgenesis (CGD), 3 with partial gonadal dysgenesis (PGD), and 3 with testicular agenesis. Molecular analysis revealed 12 heterozygous genetic changes, 4 of which were novel. One (c.416T>A) was observed in evolutionary conserved region of DMRT1 gene in a patient with CGD and was found to be probably damaging on in silico analysis. Other 3 were identified in NR5A1 gene (c.990+22 C>A, c.1387+1403T>A and p.131P), but their association with gonadal dysgenesis is not evident from our study. These genetic changes were absent in parents and 50 healthy control samples, which were also studied. With targeted sequencing approach, a molecular diagnosis was made in only one patient with 46,XY GD. The application of new genomic technologies is required for the precise evaluation of these rare genetic defects.

  16. Screening of the LIX1 gene in Japanese and Malaysian patients with SMA and/or SMA-like disorder.

    PubMed

    Sasongko, Teguh Haryo; Gunadi; Yusoff, Surini; Atif, Amin Baig; Fatemeh, Hayati; Rani, Abdulqawee; Marini, Marzuki; Ab Aziz, Che Badariah; Zabidi-Hussin, Z A M H; Nishio, Hisahide; Zilfalil, Bin Alwi

    2010-05-01

    The majority of spinal muscular atrophy (SMA) patients showed homozygous deletion or other mutations of SMN1. However, the genetic etiology of a significant number of SMA patients has not been clarified. Recently, mutation in the gene underlying cat SMA, limb expression 1 (LIX1), has been reported. Similarity in clinical and pathological features of cat and human SMA may give an insight into possible similarity of the genetic etiology. In this study, we screened for a mutation in LIX1 using direct DNA sequencing in our SMA and/or SMA-like patients who retained SMN1. A total of 33 patients were enrolled in this study, of which 22 were Japanese and 11 were Malaysians. All these patients possessed at least two copies of SMN1. We did not identify any pathogenic mutations in the coding regions or splice sites of LIX1 in the patients. In addition, we described a polymorphism within LIX1 intron 3, c.387+107A>T. We found that A-allele is significantly more frequent in SMA patients compared to normal individuals. Molecular genetic analysis of our SMA and/or SMA-like patients suggests that LIX1 is not associated with the development of their disorders. However, the number of patients analyzed in this study was very limited, and a larger study with bigger sample size is needed to confirm this result. Copyright 2009 Elsevier B.V. All rights reserved.

  17. ACOG Committee Opinion No. 442: Preconception and prenatal carrier screening for genetic diseases in individuals of Eastern European Jewish descent.

    PubMed

    2009-10-01

    Certain autosomal recessive disease conditions are more prevalent in individuals of Eastern European Jewish (Ashkenazi) descent. Previously, the American College of Obstetricians and Gynecologists recommended that individuals of Eastern European Jewish ancestry be offered carrier screening for Tay-Sachs disease, Canavan disease, and cystic fibrosis as part of routine obstetric care. Based on the criteria used to justify offering carrier screening for Tay-Sachs disease, Canavan disease, and cystic fibrosis, the American College of Obstetricians and Gynecologists' Committee on Genetics recommends that couples of Ashkenazi Jewish ancestry also should be offered carrier screening for familial dysautonomia. Individuals of Ashkenazi Jewish descent may inquire about the availability of carrier screening for other disorders. Carrier screening is available for mucolipidosis IV, Niemann-Pick disease type A, Fanconi anemia group C, Bloom syndrome, and Gaucher disease.

  18. A Drosophila screen identifies neurofibromatosis-1 genetic modifiers involved in systemic and synaptic growth

    PubMed Central

    Walker, James A; Bernards, André

    2014-01-01

    Neurofibromatosis type 1 (NF1) is caused by loss of a negative regulator of Ras oncoproteins. Unknown genetic modifiers have been implicated in NF1’s characteristic variability. Drosophila melanogaster dNf1 phenotypes include cognitive deficits and reduced growth, both of which resemble human symptoms. We recently reported results of a screen for dominant modifiers of dNf1 growth. Suppressors include the dAlk tyrosine kinase and its activating ligand, two other genes involved in Ras/ERK signal transduction, the synaptic scaffold Dap160 and the CCKLR-17D1 drosulfakinin receptor. Additional modifiers include several genes involved in cAMP/PKA signaling. Providing mechanistic insights, dAlk, jeb, and CCKLR-17D1 also suppress a dNf1 synaptic overgrowth defect, and increasing cAMP/PKA signaling in the neuroendocrine ring gland rescued the dNf1 growth deficiency. Finally, among the several suppressors identified in our screen, we specifically implicate ALK as a potential therapeutic target by showing that NF1-regulated ALK/RAS/ERK signaling is conserved in human cells. PMID:25054093

  19. Comparative genetic screens in human cells reveal new regulatory mechanisms in WNT signaling

    PubMed Central

    Lebensohn, Andres M; Dubey, Ramin; Neitzel, Leif R; Tacchelly-Benites, Ofelia; Yang, Eungi; Marceau, Caleb D; Davis, Eric M; Patel, Bhaven B; Bahrami-Nejad, Zahra; Travaglini, Kyle J; Ahmed, Yashi; Lee, Ethan; Carette, Jan E; Rohatgi, Rajat

    2016-01-01

    The comprehensive understanding of cellular signaling pathways remains a challenge due to multiple layers of regulation that may become evident only when the pathway is probed at different levels or critical nodes are eliminated. To discover regulatory mechanisms in canonical WNT signaling, we conducted a systematic forward genetic analysis through reporter-based screens in haploid human cells. Comparison of screens for negative, attenuating and positive regulators of WNT signaling, mediators of R-spondin-dependent signaling and suppressors of constitutive signaling induced by loss of the tumor suppressor adenomatous polyposis coli or casein kinase 1α uncovered new regulatory features at most levels of the pathway. These include a requirement for the transcription factor AP-4, a role for the DAX domain of AXIN2 in controlling β-catenin transcriptional activity, a contribution of glycophosphatidylinositol anchor biosynthesis and glypicans to R-spondin-potentiated WNT signaling, and two different mechanisms that regulate signaling when distinct components of the β-catenin destruction complex are lost. The conceptual and methodological framework we describe should enable the comprehensive understanding of other signaling systems. DOI: http://dx.doi.org/10.7554/eLife.21459.001 PMID:27996937

  20. Genetic Modifier Screens Reveal New Components that Interact with the Drosophila Dystroglycan-Dystrophin Complex

    PubMed Central

    Yatsenko, Andriy S.; Shcherbata, Halyna R.; Fischer, Karin A.; Maksymiv, Dariya V.; Chernyk, Yaroslava I.; Ruohola-Baker, Hannele

    2008-01-01

    The Dystroglycan-Dystrophin (Dg-Dys) complex has a capacity to transmit information from the extracellular matrix to the cytoskeleton inside the cell. It is proposed that this interaction is under tight regulation; however the signaling/regulatory components of Dg-Dys complex remain elusive. Understanding the regulation of the complex is critical since defects in this complex cause muscular dystrophy in humans. To reveal new regulators of the Dg-Dys complex, we used a model organism Drosophila melanogaster and performed genetic interaction screens to identify modifiers of Dg and Dys mutants in Drosophila wing veins. These mutant screens revealed that the Dg-Dys complex interacts with genes involved in muscle function and components of Notch, TGF-β and EGFR signaling pathways. In addition, components of pathways that are required for cellular and/or axonal migration through cytoskeletal regulation, such as Semaphorin-Plexin, Frazzled-Netrin and Slit-Robo pathways show interactions with Dys and/or Dg. These data suggest that the Dg-Dys complex and the other pathways regulating extracellular information transfer to the cytoskeletal dynamics are more intercalated than previously thought. PMID:18545683

  1. Preimplantation genetic screening- the required RCT that has not yet been carried out.

    PubMed

    Orvieto, Raoul

    2016-06-24

    The utilization of trophectoderm biopsy combined with comprehensive chromosome screening (CCS) tests for embryonic aneuploidy was recently suggested to improve IVF outcome, however, not without criticisms. The ongoing discussion on the unrestricted clinical adoption of preimplantation genetic screening (PGS) has called for a proper randomized controlled trial (RCT), aiming to further evaluate the cumulative live birth rates (LBRs) following a single oocyte retrieval, utilizing all fresh and frozen embryos. Since this study seems not to appear for various reasons, we present herewith, the hypothetical required RCT based on the hitherto published literature.After implementing data from the hitherto published literature on blastulation and aneuploidy rates, the rate of mosaicism and technical errors and implantation rates/LBRs of non-PGS day-3 and blastocyst and PGS blastocyst, we could clearly demonstrate the superiority of non-PGS embryo (day-3 and blastocyst) transfer over PGS blastocyst transfer, in terms of cumulative LBR (18.2-50 % vs 7.6-12.6 %, respectively).We therefore believe that until the proper, non-hypothetical RCT on the efficacy of this procedure will appear, PGS should be offered only under study conditions, and with appropriate informed consents.

  2. A mosaic genetic screen for genes necessary for Drosophila mushroom body neuronal morphogenesis.

    PubMed

    Reuter, John E; Nardine, Timothy M; Penton, Andrea; Billuart, Pierre; Scott, Ethan K; Usui, Tadao; Uemura, Tadashi; Luo, Liqun

    2003-03-01

    Neurons undergo extensive morphogenesis during development. To systematically identify genes important for different aspects of neuronal morphogenesis, we performed a genetic screen using the MARCM system in the mushroom body (MB) neurons of the Drosophila brain. Mutations on the right arm of chromosome 2 (which contains approximately 20% of the Drosophila genome) were made homozygous in a small subset of uniquely labeled MB neurons. Independently mutagenized chromosomes (4600) were screened, yielding defects in neuroblast proliferation, cell size, membrane trafficking, and axon and dendrite morphogenesis. We report mutations that affect these different aspects of morphogenesis and phenotypically characterize a subset. We found that roadblock, which encodes a dynein light chain, exhibits reduced cell number in neuroblast clones, reduced dendritic complexity and defective axonal transport. These phenotypes are nearly identical to mutations in dynein heavy chain Dhc64 and in Lis1, the Drosophila homolog of human lissencephaly 1, reinforcing the role of the dynein complex in cell proliferation, dendritic morphogenesis and axonal transport. Phenotypic analysis of short stop/kakapo, which encodes a large cytoskeletal linker protein, reveals a novel function in regulating microtubule polarity in neurons. MB neurons mutant for flamingo, which encodes a seven transmembrane cadherin, extend processes beyond their wild-type dendritic territories. Overexpression of Flamingo results in axon retraction. Our results suggest that most genes involved in neuronal morphogenesis play multiple roles in different aspects of neural development, rather than performing a dedicated function limited to a specific process.

  3. Genetic Screen in Drosophila melanogaster Uncovers a Novel Set of Genes Required for Embryonic Epithelial Repair

    PubMed Central

    Campos, Isabel; Geiger, Jennifer A.; Santos, Ana Catarina; Carlos, Vanessa; Jacinto, Antonio

    2010-01-01

    The wound healing response is an essential mechanism to maintain the integrity of epithelia and protect all organisms from the surrounding milieu. In the “purse-string” mechanism of wound closure, an injured epithelial sheet cinches its hole closed via an intercellular contractile actomyosin cable. This process is conserved across species and utilized by both embryonic as well as adult tissues, but remains poorly understood at the cellular level. In an effort to identify new players involved in purse-string wound closure we developed a wounding strategy suitable for screening large numbers of Drosophila embryos. Using this methodology, we observe wound healing defects in Jun-related antigen (encoding DJUN) and scab (encoding Drosophila αPS3 integrin) mutants and performed a forward genetics screen on the basis of insertional mutagenesis by transposons that led to the identification of 30 lethal insertional mutants with defects in embryonic epithelia repair. One of the mutants identified is an insertion in the karst locus, which encodes Drosophila βHeavy-spectrin. We show βHeavy-spectrin (βH) localization to the wound edges where it presumably exerts an essential function to bring the wound to normal closure. PMID:19884309

  4. A genetic screen reveals a periplasmic copper chaperone required for nitrite reductase activity in pathogenic Neisseria.

    PubMed

    Jen, Freda E-C; Djoko, Karrera Y; Bent, Stephen J; Day, Christopher J; McEwan, Alastair G; Jennings, Michael P

    2015-09-01

    Under conditions of low oxygen availability, Neisseria meningitidis and Neisseria gonorrhoeae are able to respire via a partial denitrification pathway in which nitrite is converted to nitrous oxide. In this process, nitrite reductase (AniA), a copper (Cu)-containing protein converts nitrite to NO, and this product is converted to nitrous oxide by nitric oxide reductase (NorB). NorB also confers protection against toxic NO, and so we devised a conditional lethal screen, using a norB mutant, to identify mutants that were resistant to nitrite-dependent killing. After random-deletion mutagenesis of N. meningitidis, this genetic screen identified a gene encoding a Cu chaperone that is essential for AniA function, AccA. Purified AccA binds one Cu (I) ion and also possesses a second binding site for Cu (II). This novel periplasmic Cu chaperone (AccA) appears to be essential for provision of Cu ions to AniA of pathogenic Neisseria to generate an active nitrite reductase. Apart from the Neisseria genus, AccA is distributed across a wide range of environmental Proteobacteria species. © FASEB.

  5. Prioritizing genetic testing in patients with Kallmann syndrome using clinical phenotypes.

    PubMed

    Costa-Barbosa, Flavia Amanda; Balasubramanian, Ravikumar; Keefe, Kimberly W; Shaw, Natalie D; Al-Tassan, Nada; Plummer, Lacey; Dwyer, Andrew A; Buck, Cassandra L; Choi, Jin-Ho; Seminara, Stephanie B; Quinton, Richard; Monies, Dorota; Meyer, Brian; Hall, Janet E; Pitteloud, Nelly; Crowley, William F

    2013-05-01

    The complexity of genetic testing in Kallmann syndrome (KS) is growing and costly. Thus, it is important to leverage the clinical evaluations of KS patients to prioritize genetic screening. The objective of the study was to determine which reproductive and nonreproductive phenotypes of KS subjects have implications for specific gene mutations. Two hundred nineteen KS patients were studied: 151 with identified rare sequence variants (RSVs) in 8 genes known to cause KS (KAL1, NELF, CHD7, HS6ST1, FGF8/FGFR1, or PROK2/PROKR2) and 68 KS subjects who remain RSV negative for all 8 genes. Reproductive and nonreproductive phenotypes within each genetic group were measured. Male KS subjects with KAL1 RSVs displayed the most severe reproductive phenotype with testicular volumes (TVs) at presentation of 1.5 ± 0.1 mL vs 3.7 ± 0.3 mL, P < .05 vs all non-KAL1 probands. In both sexes, synkinesia was enriched but not unique to patients with KAL1 RSVs compared with KAL1-negative probands (43% vs 12%; P < .05). Similarly, dental agenesis and digital bone abnormalities were enriched in patients with RSVs in the FGF8/FGFR1 signaling pathway compared with all other gene groups combined (39% vs 4% and 23% vs 0%; P < .05, respectively). Hearing loss marked the probands with CHD7 RSVs (40% vs 13% in non-CHD7 probands; P < .05). Renal agenesis and cleft lip/palate did not emerge as statistically significant phenotypic predictors. Certain clinical features in men and women are highly associated with genetic causes of KS. Synkinesia (KAL1), dental agenesis (FGF8/FGFR1), digital bony abnormalities (FGF8/FGFR1), and hearing loss (CHD7) can be useful for prioritizing genetic screening.

  6. Prioritizing Genetic Testing in Patients With Kallmann Syndrome Using Clinical Phenotypes

    PubMed Central

    Costa-Barbosa, Flavia Amanda; Balasubramanian, Ravikumar; Keefe, Kimberly W.; Shaw, Natalie D.; Al-Tassan, Nada; Plummer, Lacey; Dwyer, Andrew A.; Buck, Cassandra L.; Choi, Jin-Ho; Seminara, Stephanie B.; Quinton, Richard; Monies, Dorota; Meyer, Brian; Hall, Janet E.; Pitteloud, Nelly

    2013-01-01

    Context: The complexity of genetic testing in Kallmann syndrome (KS) is growing and costly. Thus, it is important to leverage the clinical evaluations of KS patients to prioritize genetic screening. Objective: The objective of the study was to determine which reproductive and nonreproductive phenotypes of KS subjects have implications for specific gene mutations. Subjects: Two hundred nineteen KS patients were studied: 151 with identified rare sequence variants (RSVs) in 8 genes known to cause KS (KAL1, NELF, CHD7, HS6ST1, FGF8/FGFR1, or PROK2/PROKR2) and 68 KS subjects who remain RSV negative for all 8 genes. Main Outcome Measures: Reproductive and nonreproductive phenotypes within each genetic group were measured. Results: Male KS subjects with KAL1 RSVs displayed the most severe reproductive phenotype with testicular volumes (TVs) at presentation of 1.5 ± 0.1 mL vs 3.7 ± 0.3 mL, P < .05 vs all non-KAL1 probands. In both sexes, synkinesia was enriched but not unique to patients with KAL1 RSVs compared with KAL1-negative probands (43% vs 12%; P < .05). Similarly, dental agenesis and digital bone abnormalities were enriched in patients with RSVs in the FGF8/FGFR1 signaling pathway compared with all other gene groups combined (39% vs 4% and 23% vs 0%; P < .05, respectively). Hearing loss marked the probands with CHD7 RSVs (40% vs 13% in non-CHD7 probands; P < .05). Renal agenesis and cleft lip/palate did not emerge as statistically significant phenotypic predictors. Conclusions: Certain clinical features in men and women are highly associated with genetic causes of KS. Synkinesia (KAL1), dental agenesis (FGF8/FGFR1), digital bony abnormalities (FGF8/FGFR1), and hearing loss (CHD7) can be useful for prioritizing genetic screening. PMID:23533228

  7. Navigating genetic diagnostics in patients with hearing loss.

    PubMed

    Sloan-Heggen, Christina M; Smith, Richard J H

    2016-12-01

    In the age of targeted genomic enrichment and massively parallel sequencing, there is no more efficient genetic testing method for the diagnosis of hereditary hearing loss. More clinical tests are on the market, which can make choosing good tests difficult. More and larger comprehensive genetic studies in patients with hearing loss have been published recently. They remind us of the importance of looking for both single nucleotide variation and copy number variation in all genes implicated in nonsyndromic hearing loss. They also inform us of how a patient's history and phenotype provide essential information in the interpretation of genetic data. Choosing the most comprehensive genetic test improves the chances of a genetic diagnosis and thereby impacts clinical care.

  8. Impact of genetic causal information on medical students' clinical encounters with an obese virtual patient: health promotion and social stigma.

    PubMed

    Persky, Susan; Eccleston, Collette P

    2011-06-01

    Health care providers will increasingly encounter information about the genetics of obesity as genetics research progresses. This study explores whether information about the genetics of obesity reduces medical student stigmatization of obese patients, and how it affects rates of health behavior-related referral. One hundred and ten third and fourth year medical students were randomly assigned to read about genetic or behavioral mechanisms of obesity, or a control topic. Students interacted with an obese virtual patient in a virtual clinic and completed a battery of measures. Rates of most health behavior screening recommendations (weight loss, exercise, and diet consultations) were lower among participants exposed to genetic causal information than control. The genetic causal information group exhibited less negative stereotyping of the patient than control, F(1,105) = 5.00, p = 0.028, but did not differ in anticipated patient adherence, F(1,105) = 3.18, p = 0.077. Information highlighting genetic contributions to obesity may lead to both positive and negative outcomes. Communication about the genetics of obesity should discuss the multi-factorial and non-deterministic nature of genetic risk.

  9. Effects of Screening for Psychological Distress on Patient Outcomes in Cancer: a Systematic Review

    PubMed Central

    Meijer, Anna; Roseman, Michelle; Delisle, Vanessa C.; Milette, Katherine; Levis, Brooke; Syamchandra, Achyuth; Stefanek, Michael E.; Stewart, Donna E.; de Jonge, Peter; Coyne, James C.; Thombs, Brett D.

    2013-01-01

    Objective Several practice guidelines recommend routine screening for psychological distress in cancer care. The objective was to evaluate the effect of screening cancer patients for psychological distress by assessing the (1) effectiveness of interventions to reduce distress among patients identified as distressed; and (2) effects of screening for distress on distress outcomes. Methods CINAHL, Cochrane, EMBASE, ISI, MEDLINE, PsycINFO, and SCOPUS databases were searched through April 6, 2011 with manual searches of 45 relevant journals, reference list review, citation tracking of included articles, and trial registry reviews through June 30, 2012. Articles in any language on cancer patients were included if they (1) compared treatment for patients with psychological distress to placebo or usual care in a randomized controlled trial (RCT); or (2) assessed the effect of screening on psychological distress in a RCT. Results There were 14 eligible RCTs for treatment of distress, and 1 RCT on the effects of screening on patient distress. Pharmacological, psychotherapy and collaborative care interventions generally reduced distress with small to moderate effects. One study investigated effects of screening for distress on psychological outcomes, and it found no improvement. Conclusion Treatment studies reported modest improvement in distress symptoms, but only a single eligible study was found on the effects of screening cancer patients for distress, and distress did not improve in screened patients versus those receiving usual care. Because of the lack of evidence of beneficial effects of screening cancer patients for distress, it is premature to recommend or mandate implementation of routine screening. PMID:23751231

  10. A Nutrition Screening Form for Female Infertility Patients.

    PubMed

    Langley, Susie

    2014-12-01

    A Nutrition Screening Form (NSF) was designed to identify lifestyle risk factors that negatively impact fertility and to provide a descriptive profile of 300 female infertility patients in a private urban infertility clinic. The NSF was mailed to all new patients prior to the initial physician's visit and self-reported data were assessed using specific criteria to determine if a nutrition referral was warranted. This observational study revealed that 43% of the women had a body mass index (BMI) <20 or ≥25 kg/m(2), known risks for infertility. Almost half reported a history of "dieting" and unrealistic weight goals potentially limiting energy and essential nutrients. A high number reported eating disorders, vegetarianism, low fat or low cholesterol diets, and dietary supplement use. Fourteen percent appeared not to supplement with folic acid, 13% rated exercise as "extremely" or "very active", and 28% reported a "high" perceived level of stress. This preliminary research demonstrated that a NSF can be a useful tool to identify nutrition-related lifestyle factors that may negatively impact fertility and identified weight, BMI, diet, exercise, and stress as modifiable risk factors deserving future research. NSF information can help increase awareness among health professionals and patients about the important link between nutrition, fertility, and successful reproductive outcomes.

  11. Does patient time spent viewing computer-tailored colorectal cancer screening materials predict patient-reported discussion of screening with providers?

    PubMed

    Sanders, Mechelle; Fiscella, Kevin; Veazie, Peter; Dolan, James G; Jerant, Anthony

    2016-08-01

    The main aim is to examine whether patients' viewing time on information about colorectal cancer (CRC) screening before a primary care physician (PCP) visit is associated with discussion of screening options during the visit. We analyzed data from a multi-center randomized controlled trial of a tailored interactive multimedia computer program (IMCP) to activate patients to undergo CRC screening, deployed in primary care offices immediately before a visit. We employed usage time information stored in the IMCP to examine the association of patient time spent using the program with patient-reported discussion of screening during the visit, adjusting for previous CRC screening recommendation and reading speed.On average, patients spent 33 minutes on the program. In adjusted analyses, 30 minutes spent using the program was associated with a 41% increase in the odds of the patient having a discussion with their PCP (1.04, 1.59, 95% CI). In a separate analysis of the tailoring modules; the modules encouraging adherence to the tailored screening recommendation and discussion with the patient's PCP yielded significant results. Other predictors of screening discussion included better self-reported physical health and increased patient activation. Time spent on the program predicted greater patient-physician discussion of screening during a linked visit.Usage time information gathered automatically by IMCPs offers promise for objectively assessing patient engagement around a topic and predicting likelihood of discussion between patients and their clinician. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  12. GAPscreener: an automatic tool for screening human genetic association literature in PubMed using the support vector machine technique.

    PubMed

    Yu, Wei; Clyne, Melinda; Dolan, Siobhan M; Yesupriya, Ajay; Wulf, Anja; Liu, Tiebin; Khoury, Muin J; Gwinn, Marta

    2008-04-22

    Synthesis of data from published human genetic association studies is a critical step in the translation of human genome discoveries into health applications. Although genetic association studies account for a substantial proportion of the abstracts in PubMed, identifying them with standard queries is not always accurate or efficient. Further automating the literature-screening process can reduce the burden of a labor-intensive and time-consuming traditional literature search. The Support Vector Machine (SVM), a well-established machine learning technique, has been successful in classifying text, including biomedical literature. The GAPscreener, a free SVM-based software tool, can be used to assist in screening PubMed abstracts for human genetic association studies. The data source for this research was the HuGE Navigator, formerly known as the HuGE Pub Lit database. Weighted SVM feature selection based on a keyword list obtained by the two-way z score method demonstrated the best screening performance, achieving 97.5% recall, 98.3% specificity and 31.9% precision in performance testing. Compared with the traditional screening process based on a complex PubMed query, the SVM tool reduced by about 90% the number of abstracts requiring individual review by the database curator. The tool also ascertained 47 articles that were missed by the traditional literature screening process during the 4-week test period. We examined the literature on genetic associations with preterm birth as an example. Compared with the traditional, manual process, the GAPscreener both reduced effort and improved accuracy. GAPscreener is the first free SVM-based application available for screening the human genetic association literature in PubMed with high recall and specificity. The user-friendly graphical user interface makes this a practical, stand-alone application. The software can be downloaded at no charge.

  13. GAPscreener: An automatic tool for screening human genetic association literature in PubMed using the support vector machine technique

    PubMed Central

    Yu, Wei; Clyne, Melinda; Dolan, Siobhan M; Yesupriya, Ajay; Wulf, Anja; Liu, Tiebin; Khoury, Muin J; Gwinn, Marta

    2008-01-01

    Background Synthesis of data from published human genetic association studies is a critical step in the translation of human genome discoveries into health applications. Although genetic association studies account for a substantial proportion of the abstracts in PubMed, identifying them with standard queries is not always accurate or efficient. Further automating the literature-screening process can reduce the burden of a labor-intensive and time-consuming traditional literature search. The Support Vector Machine (SVM), a well-established machine learning technique, has been successful in classifying text, including biomedical literature. The GAPscreener, a free SVM-based software tool, can be used to assist in screening PubMed abstracts for human genetic association studies. Results The data source for this research was the HuGE Navigator, formerly known as the HuGE Pub Lit database. Weighted SVM feature selection based on a keyword list obtained by the two-way z score method demonstrated the best screening performance, achieving 97.5% recall, 98.3% specificity and 31.9% precision in performance testing. Compared with the traditional screening process based on a complex PubMed query, the SVM tool reduced by about 90% the number of abstracts requiring individual review by the database curator. The tool also ascertained 47 articles that were missed by the traditional literature screening process during the 4-week test period. We examined the literature on genetic associations with preterm birth as an example. Compared with the traditional, manual process, the GAPscreener both reduced effort and improved accuracy. Conclusion GAPscreener is the first free SVM-based application available for screening the human genetic association literature in PubMed with high recall and specificity. The user-friendly graphical user interface makes this a practical, stand-alone application. The software can be downloaded at no charge. PMID:18430222

  14. Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine.

    PubMed

    Edwards, Janice G; Feldman, Gerald; Goldberg, James; Gregg, Anthony R; Norton, Mary E; Rose, Nancy C; Schneider, Adele; Stoll, Katie; Wapner, Ronald; Watson, Michael S

    2015-03-01

    The Perinatal Quality Foundation and the American College of Medical Genetics and Genomics, in association with the American College of Obstetricians and Gynecologists, the Society for Maternal-Fetal Medicine, and the National Society of Genetic Counselors, have collaborated to provide education for clinicians and laboratories regarding the use of expanded genetic carrier screening in reproductive medicine. This statement does not replace current screening guidelines, which are published by individual organizations to direct the practice of their constituents. As organizations develop practice guidelines for expanded carrier screening, further direction is likely. The current statement demonstrates an approach for health care providers and laboratories who wish to or who are currently offering expanded carrier screening to their patients.

  15. Haploid Genetic Screen Reveals a Profound and Direct Dependence on Cholesterol for Hantavirus Membrane Fusion

    PubMed Central

    Kleinfelter, Lara M.; Jangra, Rohit K.; Jae, Lucas T.; Herbert, Andrew S.; Mittler, Eva; Stiles, Katie M.; Wirchnianski, Ariel S.; Kielian, Margaret; Brummelkamp, Thijn R.

    2015-01-01

    ABSTRACT Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and a highly fatal hantavirus cardiopulmonary syndrome (HCPS) in the New World. No vaccines or antiviral therapies are currently available to prevent or treat hantavirus disease, and gaps in our understanding of how hantaviruses enter cells challenge the search for therapeutics. We performed a haploid genetic screen in human cells to identify host factors required for entry by Andes virus, a highly virulent New World hantavirus. We found that multiple genes involved in cholesterol sensing, regulation, and biosynthesis, including key components of the sterol response element-binding protein (SREBP) pathway, are critical for Andes virus entry. Genetic or pharmacological disruption of the membrane-bound transcription factor peptidase/site-1 protease (MBTPS1/S1P), an SREBP control element, dramatically reduced infection by virulent hantaviruses of both the Old World and New World clades but not by rhabdoviruses or alphaviruses, indicating that this pathway is broadly, but selectively, required by hantaviruses. These results could be fully explained as arising from the modest depletion of cellular membrane cholesterol that accompanied S1P disruption. Mechanistic studies of cells and with protein-free liposomes suggested that high levels of cholesterol are specifically needed for hantavirus membrane fusion. Taken together, our results indicate that the profound dependence on target membrane cholesterol is a fundamental, and unusual, biophysical property of hantavirus glycoprotein-membrane interactions during entry. PMID:26126854

  16. A Genetic Screen for Mutants with Supersized Lipid Droplets in Caenorhabditis elegans

    PubMed Central

    Li, Shiwei; Xu, Shibin; Ma, Yanli; Wu, Shuang; Feng, Yu; Cui, Qingpo; Chen, Lifeng; Zhou, Shuang; Kong, Yuanyuan; Zhang, Xiaoyu; Yu, Jialei; Wu, Mengdi; Zhang, Shaobing O.

    2016-01-01

    To identify genes that regulate the dynamics of lipid droplet (LD) size, we have used the genetically tractable model organism Caenorhabditis elegans, whose wild-type LD population displays a steady state of size with an upper limit of 3 μm in diameter. From a saturated forward genetic screen of 6.7 × 105 mutagenized haploid genomes, we isolated 118 mutants with supersized intestinal LDs often reaching 10 μm. These mutants define nine novel complementation groups, in addition to four known genes (maoc-1, dhs-28, daf-22, and prx-10). The nine groups are named drop (lipid droplet abnormal) and categorized into four classes. Class I mutants drop-5 and drop-9, similar to prx-10, are up-regulated in ACS-22-DGAT-2-dependent LD growth, resistant to LD hydrolysis, and defective in peroxisome import. Class II mutants drop-2, drop-3, drop-6, and drop-7 are up-regulated in LD growth, are resistant to LD hydrolysis, but are not defective in peroxisome import. Class III mutants drop-1 and drop-8 are neither up-regulated in LD growth nor resistant to LD hydrolysis, but seemingly up-regulated in LD fusion. Class IV mutant drop-4 is cloned as sams-1 and, different to the other three classes, is ACS-22-independent and hydrolysis-resistant. These four classes of supersized LD mutants should be valuable for mechanistic studies of LD cellular processes including growth, hydrolysis, and fusion. PMID:27261001

  17. A Genetic Screen for Mutants with Supersized Lipid Droplets in Caenorhabditis elegans.

    PubMed

    Li, Shiwei; Xu, Shibin; Ma, Yanli; Wu, Shuang; Feng, Yu; Cui, Qingpo; Chen, Lifeng; Zhou, Shuang; Kong, Yuanyuan; Zhang, Xiaoyu; Yu, Jialei; Wu, Mengdi; Zhang, Shaobing O

    2016-08-09

    To identify genes that regulate the dynamics of lipid droplet (LD) size, we have used the genetically tractable model organism Caenorhabditis elegans, whose wild-type LD population displays a steady state of size with an upper limit of 3 μm in diameter. From a saturated forward genetic screen of 6.7 × 10(5) mutagenized haploid genomes, we isolated 118 mutants with supersized intestinal LDs often reaching 10 μm. These mutants define nine novel complementation groups, in addition to four known genes (maoc-1, dhs-28, daf-22, and prx-10). The nine groups are named drop (lipid droplet abnormal) and categorized into four classes. Class I mutants drop-5 and drop-9, similar to prx-10, are up-regulated in ACS-22-DGAT-2-dependent LD growth, resistant to LD hydrolysis, and defective in peroxisome import. Class II mutants drop-2, drop-3, drop-6, and drop-7 are up-regulated in LD growth, are resistant to LD hydrolysis, but are not defective in peroxisome import. Class III mutants drop-1 and drop-8 are neither up-regulated in LD growth nor resistant to LD hydrolysis, but seemingly up-regulated in LD fusion. Class IV mutant drop-4 is cloned as sams-1 and, different to the other three classes, is ACS-22-independent and hydrolysis-resistant. These four classes of supersized LD mutants should be valuable for mechanistic studies of LD cellular processes including growth, hydrolysis, and fusion.

  18. Adult Patients' Perspectives on the Benefits and Harms of Overused Screening Tests: a Qualitative Study.

    PubMed

    Sutkowi-Hemstreet, Anne; Vu, Maihan; Harris, Russell; Brewer, Noel T; Dolor, Rowena J; Sheridan, Stacey L

    2015-11-01

    In recent years, there has been a growing interest in reducing the overuse of healthcare services. However, little is known about how patients conceptualize the benefits and harms of overused screening tests or how patients make decisions regarding these tests. To determine how patients think about the harms and benefits of overused screening tests and how they consider these and other factors when making decisions. Semi-structured, qualitative interviews. The study comprised 50 patients, ages 50-84, who had previously received or not received any of four overused screening services: 1) prostate cancer screening (men ages 50-69), 2) colon cancer screening (men and women ages 76-85), 3) osteoporosis screening (low-risk women ages 50-64), or 4) cardiovascular disease screening (low-risk men and women ages 50-85). We conducted a thematic analysis, using a hybrid inductive-deductive approach. Two independent coders analyzed interview transcriptions to identify themes and exemplifying quotes. Many patients could not name a harm of screening. When they did name harms, patients often focused on only the harms of the screening test itself and rarely mentioned harms further along the screening cascade (e.g., from follow-up testing and treatment). In contrast, patients could easily name benefits of screening, although many seemed to misunderstand or overestimate the magnitude of the benefits. Furthermore, patients described many additional factors they considered when making screening decisions, including their clinicians' recommendations, their age, family or friends' experiences with disease, and insurance coverage. This study highlights the need to help adults recognize and understand the benefits and harms of screening and make appropriate decisions about overused screening tests.

  19. Screening for substance abuse risk in cancer patients using the Opioid Risk Tool and urine drug screen.

    PubMed

    Barclay, Joshua S; Owens, Justine E; Blackhall, Leslie J

    2014-07-01

    The use of opioids for management of cancer-related pain has increased significantly and has been associated with a substantial rise in rates of substance abuse and diversion. There is a paucity of data not only on the prevalence of substance abuse in cancer patients, but also for issues of drug use and diversion in family caregivers. This study aimed to evaluate the frequency of risk factors for substance abuse and diversion, and abnormal urine drug screens in cancer patients receiving palliative care. A retrospective chart review was performed for patients with cancer who were seen in the University of Virginia Palliative Care Clinic during the month of September 2012. We evaluated Opioid Risk Tool variables and total scores, insurance status, and urine drug screen results. Of the 114 cancer patients seen in September 2012, the mean Opioid Risk Tool score was 3.79, with 43% of patients defined as medium to high risk. Age (16-45 years old, 23%) and a personal history of alcohol (23%) or illicit drugs (21%) were the most common risk factors identified. We obtained a urine drug screen on 40% of patients, noting abnormal findings in 45.65%. Opioids are an effective treatment for cancer-related pain, yet substantial risk for substance abuse exits in the cancer population. Screening tools, such as the Opioid Risk Tool, should be used as part of a complete patient assessment to balance risk with appropriate relief of suffering.

  20. Does Patient Time Spent Viewing Computer-Tailored Colorectal Cancer Screening Materials Predict Patient-Reported Discussion of Screening with Providers?

    ERIC Educational Resources Information Center

    Sanders, Mechelle; Fiscella, Kevin; Veazie, Peter; Dolan, James G.; Jerant, Anthony

    2016-01-01

    The main aim is to examine whether patients' viewing time on information about colorectal cancer (CRC) screening before a primary care physician (PCP) visit is associated with discussion of screening options during the visit. We analyzed data from a multi-center randomized controlled trial of a tailored interactive multimedia computer program…

  1. Does Patient Time Spent Viewing Computer-Tailored Colorectal Cancer Screening Materials Predict Patient-Reported Discussion of Screening with Providers?

    ERIC Educational Resources Information Center

    Sanders, Mechelle; Fiscella, Kevin; Veazie, Peter; Dolan, James G.; Jerant, Anthony

    2016-01-01

    The main aim is to examine whether patients' viewing time on information about colorectal cancer (CRC) screening before a primary care physician (PCP) visit is associated with discussion of screening options during the visit. We analyzed data from a multi-center randomized controlled trial of a tailored interactive multimedia computer program…

  2. Genome-wide in silico screening for microRNA genetic variability in livestock species.

    PubMed

    Jevsinek Skok, D; Godnic, I; Zorc, M; Horvat, S; Dovc, P; Kovac, M; Kunej, T

    2013-12-01

    MicroRNAs are a class of non-coding RNAs that post-transcriptionally regulate target gene expression. Previous studies have shown that microRNA gene variability can interfere with its function, resulting in phenotypic variation. Polymorphisms within microRNA genes present a source of novel biomarkers for phenotypic traits in animal breeding. However, little is known about microRNA genetic variability in livestock species, which is also due to incomplete data in genomic resource databases. There