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PGD patients' and providers' attitudes to the use and regulation of preimplantation genetic diagnosis  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) providers and patients have a vested interest in policy related to the use and regulation of PGD. To understand their experiences and attitudes, 32 in-depth interviews were conducted. Participants included 13 people at risk of transmitting a single-gene alteration to their children (10\\/13 had actually used PGD to try to have an unaffected child) and 19

Andrea L Kalfoglou; Joan Scott; Kathy Hudson



Preimplantation genetic diagnosis (PGD) influences adrenal development and response to cold stress in resulting mice.  


Preimplantation genetic diagnosis (PGD) has gained widespread application in clinical medicine and hence the health of PGD offspring needs to be systematically assessed. Given the critical role of the stress response in growth and health, assessments of the development and function of the stress system might help to clarify the health outcomes of PGD. In this study, we constructed a PGD-conceived mouse model and used naturally conceived mice as controls; we used this model to evaluate the potential effect of PGD procedures on the stress system of the offspring. Serum and tissues of stress organs, namely the hypothalamus, locus coeruleus and adrenal gland, were collected from 5-week-old mice in the basal state or after cold stress. The serum levels of stress-related hormones and the structural and functional indices of the stress organs were then examined. In the basal state, ultrastructural abnormalities and low expression of genes involved in steroid hormone synthesis were found in the adrenals of the PGD mice, which had low corticosterone and high epinephrine levels compared with those of control mice. After acute cold stress, the PGD mice continued to show structural and glucocorticoid secretion abnormalities resulting in a late response to the environmental change. Thus, our study indicates that PGD manipulations affect adrenal development, result in structural and functional abnormalities of the adrenals in the offspring and influence their reactivity and adaptability to cold stress. PMID:24104561

Zeng, Yan; Lv, Zhuo; Gu, Leilei; Wang, Liu; Zhou, Zuomin; Zhu, Hui; Zhou, Qi; Sha, Jiahao



Preimplantation Genetic Diagnosis (PGD) on In-Vitro Fertilization (IVF) Websites: Presentations of Risks, Benefits and Other Information  

PubMed Central

Objective To examine information on Preimplantation Genetic Diagnosis (PGD) presented on In-Vitro Fertilization (IVF) clinic websites. Design We systematically sampled every third IVF clinic on the 2004 CDC provider list. Setting The Internet. Patients None. Interventions None. Main Outcome Measures Benefits, risks and other types of information mentioned regarding PGD. Results Of 135 sites examined, 88.1% had websites, and 70% mentioned PGD, of which 27% were university/hospital-based and 63% were private clinics. Sites mentioning PGD listed uses/benefits of PGD far more than the risks involved. Of these sites, 76% described testing for single gene diseases, but fewer mentioned risks of missing target diagnoses (35%), or risks for loss of embryo (18%); and 14% described PGD as new or controversial. Private clinics were more likely than other programs to: be on either the East or West Coasts; list certain PGD risks (e.g., diagnostic error); note that PGD was new or controversial; reference source of PGD information; provide accuracy rates of genetic testing of embryos; and offer gender selection for social reasons. Conclusions Most IVF clinics advertise PGD on-line, but the scope and quality of information about it varies widely, emphasizing benefits while minimizing risks. Clinics and patients may benefit from more thorough and consistent presentation of PGD, drawing on available evidence to best provide a realistic portrayal of PGD. PMID:18829009

Klitzman, Robert; Zolovska, Beata; Folberth, William; Sauer, Mark V.; Chung, Wendy; Appelbaum, Paul



Accuracy of preimplantation genetic diagnosis (PGD) of single gene and chromosomal disorders  

SciTech Connect

We have developed a polar body inferred approach for preconception diagnosis of single gene and chromosomal disorders. Preconception PCR or FISH analysis was performed in a total of 310 first polar bodies for the following genetic conditions: cystic fibrosis, hemophilia A, alpha-1-antitrypsin deficiency, Tay Sachs disease, retinitis pigmentosa and common chromosomal trisomies. An important advantage of this approach is the avoidance of sperm (DNA) contamination, which is the major problem of PGD. We are currently applying FISH analysis of biopsied blastomeres, in combination with PCR or separately, and have demonstrated a significant improvement of the accuracy of PGD of X-linked disorders at this stage. Our data have also demonstrated feasibility of the application of FISH technique for PGD of chromosomal disorders. It was possible to detect chromosomal non-disjunctions and chromatid malsegregations in the first meiotic division, as well as to evaluate chromosomal mutations originating from the second meiotic nondisjunction.

Verlinsky, Y.; Strom, C.; Rechitsky, S. [Reproductive Genetics Institute, Chicage, IL (United States)] [and others



PGD patients' and providers' attitudes to the use and regulation of preimplantation genetic  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) providers and patients have a vested interest in policy related to the use and regulation of PGD. To understand their experiences and attitudes, 32 in-depth interviews were conducted. Participants included 13 people at risk of transmitting a single-gene alteration to their children (10\\/13 had actually used PGD to try to have an unaffected child) and 19

Andrea L Kalfoglou; Joan Scott; Kathy Hudson


Reprogenetics: Preimplantational genetics diagnosis  

PubMed Central

Preimplantational Genetics Diagnosis (PGD) is requested by geneticists and reproductive specialists. Usually geneticists ask for PGD because one or both members of the couple have an increased genetic risk for having an affected offspring. On the other hand, reproductive specialists ask for embryo aneuploidy screening (PGS) to assures an euploid embryo transfer, with the purpose to achieve an ongoing pregnancy, although the couple have normal karyotypes. As embryonic aneuploidies are responsible for pre and post implantation abortions, it is logical to considerer that the screening of the embryonic aneuploidies prior to embryo transfer could improve the efficiency of the in vitro fertilization procedures. Nevertheless, it is still premature to affirm this until well-designed clinical trials were done, especially in women of advanced age where the rate of embryos with aneuploidies is much greater. Although the indications of PGD are similar to conventional prenatal diagnosis (PND), PGD has less ethical objections than the PND. As with the PGD/PGS results only unaffected embryos are transferred, both methods can avoid the decision to interrupt the pregnancy due to a genetic problem; this makes an important difference when compared to conventional prenatal diagnosis. PMID:24764761

Coco, Roberto



Preimplantation genetic diagnosis for inherited neurological disorders.  


Preimplantation genetic diagnosis (PGD) is an option for couples at risk of having offspring with an inherited debilitating or fatal neurological disorder who wish to conceive a healthy child. PGD has been carried out for conditions with various modes of inheritance, including spinal muscular atrophy, Huntington disease, fragile X syndrome, and chromosomal or mitochondrial disorders, and for susceptibility genes for cancers with nervous system involvement. Most couples at risk of transmitting a genetic mutation would opt for PGD over prenatal testing and possible termination of a pregnancy. The aim of this Perspectives article is to assist neurologists in counselling and treating patients who wish to explore the option of PGD to enable conception of an unaffected child. PGD can be accomplished for most disorders in which the genetic basis is known, and we argue that it is time for clinicians and neurological societies to consider the evidence and to formulate guidelines for the responsible integration of PGD into modern preventative neurology. PMID:24866878

Tur-Kaspa, Ilan; Jeelani, Roohi; Doraiswamy, P Murali



The Ethics of Preimplantation Genetic Diagnosis  

NSDL National Science Digital Library

In this video excerpt from NOVA, learn about the advantages, disadvantages, and ethical implications of preimplantation genetic diagnosis, or PGD, a technique used to screen embryos created through in vitro fertilization for diseases.

Foundation, Wgbh E.



Clinical pregnancy following pre-implantation genetic diagnosis for cystic fibrosis.  


Pre-implantation genetic diagnosis (PGD) is an established alternative to prenatal testing for couples at risk of transmitting genetic disorders such as cystic fibrosis (CF).PGD screens pre-implantation embryos, allowing the safe transfer of those identified as unaffected. Awareness of CF carrier status in Ireland is increasing following the introduction of neonatal screening in 2011. PGD is the most acceptable reproductive strategy for many at risk Irish couples but until now the treatment necessitated travelling abroad. In 2012, the Irish Medicines Board licenced two Irish fertility clinics to carry out embryo biopsy for PGD. This is the first reported clinical pregnancy following PGD carried out in Ireland. PMID:25282962

Zhang, X; Dineen, T; Flanagan, J; Kovacs, A; O'Driscoll, A; O'Callaghan, J; Mihart, R; Geisler, M; Wiegandt, P; Waterstone, J



Preimplantation genetic diagnosis: State of the ART 2011  

Microsoft Academic Search

For the last 20 years, preimplantation genetic diagnosis (PGD) has been mostly performed on cleavage stage embryos after the\\u000a biopsy of 1–2 cells and PCR and FISH have been used for the diagnosis. The main indications have been single gene disorders\\u000a and inherited chromosome abnormalities. Preimplantation genetic screening (PGS) for aneuploidy is a technique that has used\\u000a PGD technology to examine

Joyce C. Harper; Sioban B. SenGupta


Methods in preimplantation genetic diagnosis * * Chapter taken from a forthcoming book in Spanish on Modern Assisted Conception edited by RG Edwards and F Risquez. Supported by Serono  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) is a new strategy, orientated toward primary prevention of congenital anomalies in couples with reproductive risk, such as advanced maternal age, carriers of chromosomal abnormalities, and carriers of monogenic conditions. For these patients, PGD is an acceptable alternative to prenatal diagnosis, mainly in those countries where pregnancy interruption is forbidden by law. PGD effectively avoids the

Luis Arturo Lizcano Gil; Carolina Lucena; Elkin Lucena



Preimplantation genetic diagnosis: public policy and public attitudes  

Microsoft Academic Search

In vitro fertilization (IVF) and genetic testing each present a host of issues that are technically, legally, and ethically complicated. Nevertheless, the worlds of genetic testing and assisted reproduction have converged with the advent of preimplantation genetic diagnosis (PGD), which allows par- ents to choose which embryos to transfer to the mother's womb on the basis of genetic test results.

Kathy L. Hudson



Comparison of attitudes regarding preimplantation genetic diagnosis among patients with hereditary cancer syndromes.  


Preimplantation genetic diagnosis (PGD) allows couples to avoid having a child with an inherited condition, potentially reducing cancer burden in families with a hereditary cancer predisposition. This study investigated and compared awareness and acceptance of PGD among patients with different hereditary cancer syndromes. Questionnaires were mailed to 984 adults with hereditary breast and ovarian cancer, Lynch syndrome, familial adenomatous polyposis, or multiple endocrine neoplasia type 1 or 2. Associations between clinical, demographic, and psychosocial factors and awareness and acceptance of PGD were examined. Of 370 respondents (38 % return rate), 28 % felt their syndrome impacted family planning, 24 % were aware of PGD, 72 % felt that PGD should be offered, 43 % would consider using PGD, and 29 % were uncertain. Family experience and syndrome-specific characteristics, such as disease severity, quality of life and availability of medical interventions as well as gender, family planning stage, and religiosity impact perceptions of the acceptability of PGD, though a high level of uncertainty exists. Hereditary cancer patients lack awareness of PGD despite feeling that PGD should be offered, highlighting the need for education on this topic. While we found attitudes about the acceptability of PGD to be generally similar to those reported in the literature and of genetics and ethics experts, we observed similarities and differences between syndromes that provide insight into why some hereditary cancer patients may find PGD more acceptable than others. PMID:24072553

Rich, Thereasa A; Liu, Mei; Etzel, Carol J; Bannon, Sarah A; Mork, Maureen E; Ready, Kaylene; Saraiya, Devki S; Grubbs, Elizabeth G; Perrier, Nancy D; Lu, Karen H; Arun, Banu K; Woodard, Terri L; Schover, Leslie R; Litton, Jennifer K



Comparison of Attitudes Regarding Preimplantation Genetic Diagnosis Among Patients with Hereditary Cancer Syndromes  

PubMed Central

Introduction Preimplantation Genetic Diagnosis (PGD) allows couples to avoid having a child with an inherited condition, potentially reducing cancer burden in families with a hereditary cancer predisposition. This study investigated awareness and acceptance of PGD among patients with hereditary cancer syndromes. Methods Questionnaires were mailed to 984 adults with hereditary breast and ovarian cancer, Lynch syndrome, familial adenomatous polyposis, or multiple endocrine neoplasia type 1 or 2. Associations between clinical, demographic, and psychosocial factors and awareness and acceptance of PGD were examined. Results Of 370 respondents (38% return rate), 28% felt their syndrome impacted family planning, 24% were aware of PGD, 72% felt that PGD should be offered, 43% would consider using PGD, and 29% were uncertain. Family experience and syndrome-specific characteristics, such as disease severity, quality of life and availability of medical interventions as well as gender, family planning stage, and religiosity impact perceptions of the acceptability of PGD, though a high level of uncertainty exists. Conclusion Hereditary cancer patients' opinions about the acceptability of PGD are similar to those of genetics and ethical experts. Patients should be told about PGD given that most had not heard of PGD, but feel that PGD should be offered. PMID:24072553

Rich, Thereasa A.; Liu, Mei; Etzel, Carol J.; Bannon, Sarah A.; Mork, Maureen E.; Ready, Kaylene; Saraiya, Devki S.; Grubbs, Elizabeth G.; Perrier, Nancy D.; Lu, Karen H.; Arun, Banu K.; Woodard, Terri L.; Schover, Leslie R.; Litton, Jennifer K.



Patient Education and Informed Consent for Preimplantation Genetic Diagnosis: Health Literacy for Genetics and Assisted Reproductive Technology  

PubMed Central

Introduction Innovative applications of genetic testing have emerged within the field of assisted reproductive technology through preimplantation genetic diagnosis (PGD). As in all forms of genetic testing, adequate genetic counseling and informed consent are critical. Despite the growing recognition of the role of informed consent in genetic testing, there is little data available about how this process occurs in the setting of PGD. Methods A cross sectional study of IVF clinics offering PGD in the U.S. was conducted to assess patient education and informed consent practices. Descriptive data were collected with a self-administered survey instrument. Results More than half of the clinics offering PGD required genetic counseling prior to PGD (56%). Genetic counseling was typically performed by certified genetic counselors (84 %). Less than half (37%) of the clinics required a separate informed consent process for genetic testing of embryonic cells. At a majority of those clinics requiring a separate informed consent for genetic testing (54%), informed consent for PGD and genetic testing took place as a single event before beginning IVF procedures. Conclusions The results suggest that patient education and informed consent practices for PGD have yet to be standardized. These findings warrant the establishment of professional guidelines for patient education and informed consent specific to embryonic genetic testing. PMID:19652605

McGowan, Michelle L.; Burant, Chris; Moran, Rocio; Farrell, Ruth



Preimplantation Genetic Diagnosis in Marfan Syndrome  

PubMed Central

Marfan syndrome (MFS) is a systemic hereditable disorder of the connective tissue with mainly cardiovascular manifestations, such as aortic dilatation and dissection. We describe a case of a 32-year-old Caucasian woman, clinically asymptomatic with MFS who presented for genetic consultation to prevent the transmission of disease to her offspring. She underwent controlled ovarian stimulation (COH), in vitro fertilization (IVF) combined with preimplantation genetic diagnosis (PGD), and a singleton pregnancy with positive fetal heart rate was revealed. At 34 weeks' gestation she delivered vaginally a healthy premature male infant weighting 2440 gr. The patient remained asymptomatic during pregnancy, delivery, and 3 months postpartum. It is has to be mentioned that the availability of PGD is essential to prevent the transmission of disease to the next generation. PMID:23781359

Vlahos, N. F.; Triantafyllidou, O.; Vitoratos, N.; Grigoriadis, C.; Creatsas, G.



State Intervention in Couples’ Reproductive Decisions: Socioethical Reflections Based on the Practice of Preimplantation Genetic Diagnosis in France  

Microsoft Academic Search

Adopting socioethical and anthropological perspectives, this article addresses the impact of state intervention in the reproductive life of couples who consult for preimplantation genetic diagnosis (PGD) in France. Our main objective is to identify and analyze the socioethical problems flowing from French legislation as related to PGD and from its implementation. Methods included review and analysis of the relevant literature,

Chantal Bouffard; Julie-Kim Godin; Bénédicte Bévière



Anticipating issues related to increasing preimplantation genetic diagnosis use: a research agenda.  


Increasing use of preimplantation genetic diagnosis (PGD) poses numerous clinical, social, psychological, ethical, legal and policy dilemmas, many of which have received little attention. Patients and providers are now considering and using PGD for a widening array of genetic disorders, and patients may increasingly seek 'designer babies.' In the USA, although governmental oversight policies have been discussed, few specific guidelines exist. Hence, increasingly, patients and providers will face challenging ethical and policy questions of when and for whom to use PGD, and how it should be financed. These issues should be better clarified and addressed through collection of data concerning the current use of PGD in the USA, including factors involved in decision making about PGD use, as well as the education of the various communities that are, and should be, involved in its implementation. Improved understanding of these issues will ultimately enhance the development and implementation of future clinical guidelines and policies. PMID:18644221

Klitzman, Robert; Appelbaum, Paul S; Chung, Wendy; Sauer, Mark



Pregnancy after preimplantation genetic diagnosis for brachydactyly type B  

Microsoft Academic Search

Brachydactyly type B (BDB) is an autosomal dominant disease caused by mutations in the ROR2 gene. Truncating mutations lead to the severe form of the disease, which is characterized by terminal deficiency of fingers and toes. Preimplantation genetic diagnosis (PGD) was carried out in a family suffering from severe BDB. The family was screened for mutations in exons 8 and

Ali Hellani; Khaled Abu-Amero; Joseph Azouri; Hadeel Al-Sharif; Hamish Barblet; Siham El-Akoum



Paternal gonadal mosaicism detected in a couple with recurrent abortions undergoing PGD: FISH analysis of sperm nuclei proves valuable  

Microsoft Academic Search

Many couples are now seeking preimplantation genetic diagnosis (PGD) and fluorescence in-situ hybridization (FISH) as an alternative approach to avoid spontaneous abortion by ensuring transfer of presumed chromosomally normal embryos. This case report describes unexpected findings in a couple having three spontaneous abortions and two failed IVF cycles. In two IVF PGD cycles, four of 13 (30.8%) embryos (blastomeres) demonstrated

Charintip Somprasit; Monica Aguinaga; Pauline L Cisneros; Sergey Torsky; Sandra A Carson; John E Buster; Paula Amato; Sallie Lou McAdoo; Joe Leigh Simpson; Farideh Z Bischoff



FISH for Pre-implantation Genetic Diagnosis  

PubMed Central

Pre-implantation genetic diagnosis (PGD) is an established alternative to pre-natal diagnosis, and involves selecting pre-implantation embryos from a cohort generated by assisted reproduction technology (ART). This selection may be required because of familial monogenic disease (e.g. cystic fibrosis), or because one partner carries a chromosome rearrangement (e.g. a two-way reciprocal translocation). PGD is available for couples who have had previous affected children, and/or in the case of chromosome rearrangements, recurrent miscarriages, or infertility. Oocytes aspirated following ovarian stimulation are fertilized by in vitro immersion in semen (IVF) or by intracytoplasmic injection of an individual spermatozoon (ICSI). Pre-implantation cleavage-stage embryos are biopsied, usually by the removal of a single cell on day 3 post-fertilization, and the biopsied cell is tested to establish the genetic status of the embryo. Fluorescence in situ hybridization (FISH) on the fixed nuclei of biopsied cells with target-specific DNA probes is the technique of choice to detect chromosome imbalance associated with chromosome rearrangements, and to select female embryos in families with X-linked disease for which there is no mutation-specific test. FISH has also been used to screen embryos for spontaneous chromosome aneuploidy (also known as PGS or PGD-AS) in order to try and improve the efficiency of assisted reproduction; however, the predictive value of this test using the spreading and FISH technique described here is likely to be unacceptably low in most people's hands and it is not recommended for routine clinical use. We describe the selection of suitable probes for single-cell FISH, spreading techniques for blastomere nuclei, and in situ hybridization and signal scoring, applied to PGD in a clinical setting. PMID:21403624

Scriven, Paul N.; Kirby, Toby L.; Ogilvie, Caroline Mackie



Preimplantation genetic diagnosis and rational choice under risk or uncertainty.  


In this paper I present an argument in favour of a parental duty to use preimplantation genetic diagnosis (PGD). I argue that if embryos created in vitro were able to decide for themselves in a rational manner, they would sometimes choose PGD as a method of selection. Couples, therefore, should respect their hypothetical choices on a principle similar to that of patient autonomy. My thesis shows that no matter which moral doctrine couples subscribe to, they ought to conduct the PGD procedure in the situations when it is impossible to implant all of the created embryos and if there is a significant risk for giving birth to a child with a serious condition. PMID:24835332

Zuradzki, Tomasz



An evaluation of PGD in clinical genetic services through 3 years application for prevention of beta-thalassaemia major and sickle cell thalassaemia  

Microsoft Academic Search

PGD represents an alternative within prenatal diagnosis services, which avoids terminating affected on-going pregnancies. In Greece, prevention programmes for haemoglobinopathies, including the option of prenatal diagnosis, are well established. Following optimization of a single-cell genotyping strategy (designed to be applicable for the majority of b-thalassaemia major or sickle thalassaemia genotype interactions) along with close collaboration with an IVF unit, we

Joanne Traeger-Synodinos; Christina Vrettou; Giles Palmer; Maria Tzetis; Minas Mastrominas; Stephen Davies; Emmanuel Kanavakis



Effect of infertility, maternal age, and number of previous miscarriages on the outcome of preimplantation genetic diagnosis for idiopathic recurrent pregnancy loss  

Microsoft Academic Search

Objective: To determine whether preimplantation genetic diagnosis (PGD) would decrease spontaneous abortion rates in patients with idiopathic recurrent pregnancy loss (RPL). Design: Controlled clinical study. Setting: IVF center and PGD reference laboratory. Patient(s): Patients with RPL with no known etiology. Intervention(s): Preimplantation genetic diagnosis by fluorescence in situ hybridization analyzing nine chromo- somes. Main Outcome Measure(s): The spontaneous abortion rate

John G. Garrisi; Pere Colls; Kathleen M. Ferry; Xhezong Zheng; Margarett G. Garrisi; Santiago Munné



The politics of human embryo research and the motivation to achieve PGD  

PubMed Central

This article reports a historical study of factors influencing the achievement of clinical preimplantation genetic diagnosis (PGD) in 1990, 22 years after its first demonstration in animals. During the 1970s, research on PGD continued in large farm animals, but serious interest in human PGD was not evident until 1986. First, interest in PGD during the 1970s waned with the advent of prenatal testing, which for gynaecologists was clinically more familiar, technically simpler and ethically less challenging than IVF. Indeed, IVF was viewed with widespread suspicion until the first IVF births in 1978. Second, interest in clinical PGD was stimulated by the UK Parliamentary reaction against human embryo research that greeted the Warnock Report in 1984. This hostility led scientists to initiate a pro-research campaign, further galvanized in 1985 by MP Enoch Powell’s bid to ban such research. However, while Powell abhorred embryo research, he approved of PGD, a stance that divided the anti-research lobby. Accordingly, the campaigners for research emphasized that it was needed to achieve PGD. Powell demanded evidence of such projects and PGD research increased from 1986. It is concluded that UK political debates on embryo research played a critical role in stimulating the achievement of clinical PGD. Human pregnancies following preimplantation genetic diagnosis (PGD) for embryo sex were announced in 1990, 22 years after the technique was pioneered in animals. PGD in humans required not only technological advances, such as IVF and sensitive diagnostic tests, but also the motivation to develop and apply them. Our historical analysis shows that, although research on PGD continued in large farm animals during the 1970s, and techniques of the required sensitivity were developed on mouse embryo models, interest in clinical PGD was not evident until 1986. Two factors stimulated this sudden change in motivation. First, interest in PGD was depressed during the 1970s by the advent of prenatal diagnostic techniques, which for gynaecologists were clinically, technically and ethically less challenging than IVF. IVF was then regarded with a suspicion that only started to wane in the early 1980s following the first IVF births. Second, the UK Parliamentary reaction against human embryo research that greeted the Warnock Report in 1984 provided a positive stimulus to clinical PGD by prompting scientists to form a pro-research lobby, which was further galvanized in early 1985 by MP Enoch Powell’s almost-successful bid to ban human embryo research. We show that while Powell abhorred embryo research, he approved of PGD, a stance that fractured the unity of the anti-research lobby. Accordingly, the pro-research lobby emphasized that embryo research was needed to achieve PGD. Powell demanded evidence of such projects, thereby, we argue, stimulating PGD research from 1986. Our evidence shows that UK political debates about PGD played a critical role in stimulating the achievement of PGD clinically. PMID:21397558

Theodosiou, Anastasia A.; Johnson, Martin H.



The politics of human embryo research and the motivation to achieve PGD.  


This article reports a historical study of factors influencing the achievement of clinical preimplantation genetic diagnosis (PGD) in 1990, 22 years after its first demonstration in animals. During the 1970s, research on PGD continued in large farm animals, but serious interest in human PGD was not evident until 1986. First, interest in PGD during the 1970s waned with the advent of prenatal testing, which for gynaecologists was clinically more familiar, technically simpler and ethically less challenging than IVF. Indeed, IVF was viewed with widespread suspicion until the first IVF births in 1978. Second, interest in clinical PGD was stimulated by the UK Parliamentary reaction against human embryo research that greeted the Warnock Report in 1984. This hostility led scientists to initiate a pro-research campaign, further galvanized in 1985 by MP Enoch Powell's bid to ban such research. However, while Powell abhorred embryo research, he approved of PGD, a stance that divided the anti-research lobby. Accordingly, the campaigners for research emphasized that it was needed to achieve PGD. Powell demanded evidence of such projects and PGD research increased from 1986. It is concluded that UK political debates on embryo research played a critical role in stimulating the achievement of clinical PGD. Human pregnancies following preimplantation genetic diagnosis (PGD) for embryo sex were announced in 1990, 22 years after the technique was pioneered in animals. PGD in humans required not only technological advances, such as IVF and sensitive diagnostic tests, but also the motivation to develop and apply them. Our historical analysis shows that, although research on PGD continued in large farm animals during the 1970s, and techniques of the required sensitivity were developed on mouse embryo models, interest in clinical PGD was not evident until 1986. Two factors stimulated this sudden change in motivation. First, interest in PGD was depressed during the 1970s by the advent of prenatal diagnostic techniques, which for gynaecologists were clinically, technically and ethically less challenging than IVF. IVF was then regarded with a suspicion that only started to wane in the early 1980s following the first IVF births. Second, the UK Parliamentary reaction against human embryo research that greeted the Warnock Report in 1984 provided a positive stimulus to clinical PGD by prompting scientists to form a pro-research lobby, which was further galvanized in early 1985 by MP Enoch Powell's almost-successful bid to ban human embryo research. We show that while Powell abhorred embryo research, he approved of PGD, a stance that fractured the unity of the anti-research lobby. Accordingly, the pro-research lobby emphasized that embryo research was needed to achieve PGD. Powell demanded evidence of such projects, thereby, we argue, stimulating PGD research from 1986. Our evidence shows that UK political debates about PGD played a critical role in stimulating the achievement of PGD clinically. PMID:21397558

Theodosiou, Anastasia A; Johnson, Martin H



PGD for a carrier of an intrachromosomal insertion using aCGH.  


Abstract Intrachromosomal insertions are rare and difficult to diagnose. However, making the correct diagnosis is critical for genetic risk assessment, and prenatal and preimplantation genetic diagnosis outcomes. We present a case of preimplantation genetic diagnosis (PGD) using array comparative genomic hybridization (aCGH) following trophectoderm biopsy of embryos created after in vitro fertilization for a carrier of an intrachromosomal insertion on chromosome 1 [46,XX, ins(1)(q44q23q32.1)]. The PGD analysis of 6 blastocysts demonstrated 67% unbalanced embryos. No pregnancy was achieved after the transfer of 2 euploid embryos. To the best of our knowledge, this is the first reported case of PGD using aCGH following trophectoderm biopsy for a carrier of an intrachromosomal insertion. PMID:25247722

Jones, Claire Ann; Kolomietz, Elena; Maire, Georges; Vlasschaert, Matthew; Joseph-George, Ann M; Myles-Reid, Diane; Chong, Karen; Chitayat, David; Arthur, Rebecca



[Extending preimplantation genetic diagnosis to HLA typing: the French exception].  


Umut-Talha, a "sibling savior", was born on 26 January 2011 at Beclère Hospital after embryo selection at the Paris preimplantation genetic diagnosis (PGD) center. His birth revived the controversy over "double PGD". This procedure, authorized in France since 2006, allows couples who already have a child with a serious, incurable genetic disease, to opt for PGD in order to select a healthy embryo that is HLA-matched to the affected sibling and who may thus serve as an ombilical cord blood donor. The procedure is particularly complex and the baby take-home rate is still very low. Double PGD is strictly regulated in France, and candidate couples must first receive individual authorization from the Biomedicine Agency. In our experience, these couples have a strong desire to have children, as reflected by the large number of prior spontaneous pregnancies (25% of couples). Likewise, most of these couples request embryo transfer even when there is no HLA-matched embryo, which accounts for more than half of embryo transfers. The controversy surrounding this practice has flared up again in recent weeks, over the concepts of "designer babies" and "double savior siblings" (the baby is selected to be free of the hereditary disease, and may also serve as a stem cell donor for the affected sibling). PMID:22375367

Steffann, Julie; Frydman, Nelly; Burlet, Philippe; Gigarel, Nadine; Hesters, Laetitia; Kerbrat, Violaine; Lamazou, Frédéric; Munnich, Arnold; Frydman, René



Preimplantation genetic diagnosis reduces pregnancy loss in women aged 35 years and older with a history of recurrent miscarriages  

Microsoft Academic Search

Objective: To determine whether preimplantation genetic diagnosis (PGD) and transfer of euploid embryos would decrease spontaneous abortion rates in recurrent miscarriage (RM) patients. Design: Controlled clinical study. Setting: In vitro fertilization centers and PGD reference laboratory. Patient(s): Recurrent-miscarriage patients with three or more prior lost pregnancies with no known etiology. Intervention(s): Biopsy of a single blastomere from each day 3

Santiago Munné; Serena Chen; Jill Fischer; Pere Colls; Xuezong Zheng; John Stevens; Tomas Escudero; Maria Oter; Joe Leigh Simpson; Jacques Cohen


Preimplantation genetic diagnosis for a Chinese family with autosomal recessive Meckel-Gruber syndrome type 3 (MKS3).  


Meckel-Gruber syndrome type 3 is an autosomal recessive genetic defect caused by mutations in TMEM67 gene. In our previous study, we have identified a homozygous TMEM67 mutation in a Chinese family exhibiting clinical characteristics of MKS3, which provided a ground for further PGD procedure. Here we report the development and the first clinical application of the PGD for this MKS3 family. Molecular analysis protocol for clinical PGD procedure was established using 50 single cells in pre-clinical set-up. After whole genomic amplification by multiple displacement amplification with the DNA from single cells, three techniques were applied simultaneously to increase the accuracy and reliability of genetic diagnosis in single blastomere, including real-time PCR with Taq Man-MGB probe, haplotype analysis with polymorphic STR markers and Sanger sequencing. In the clinical PGD cycle, nine embryos at cleavage-stage were biopsied and subjected to genetic diagnosis. Two embryos diagnosed as free of TMEM67 mutation were transferred and one achieving normal pregnancy. Non-invasive prenatal assessment of trisomy 13, 18 and 21 by multiplex DNA sequencing at 18 weeks' gestation excluded the aneuploidy of the analyzed chromosomes. A healthy boy was delivered by cesarean section at 39 weeks' gestation. DNA sequencing from his cord blood confirmed the result of genetic analysis in the PGD cycle. The protocol developed in this study was proved to be rapid and safe for the detection of monogenic mutations in clinical PGD cycle. PMID:24039893

Lu, Yanping; Peng, Hongmei; Jin, Zhanguo; Cheng, Jing; Wang, Shufang; Ma, Minyue; Lu, Yu; Han, Dongyi; Yao, Yuanqing; Li, Yali; Yuan, Huijun



Preimplantation Genetic Diagnosis for a Chinese Family with Autosomal Recessive Meckel-Gruber Syndrome Type 3 (MKS3)  

PubMed Central

Meckel-Gruber syndrome type 3 is an autosomal recessive genetic defect caused by mutations in TMEM67 gene. In our previous study, we have identified a homozygous TMEM67 mutation in a Chinese family exhibiting clinical characteristics of MKS3, which provided a ground for further PGD procedure. Here we report the development and the first clinical application of the PGD for this MKS3 family. Molecular analysis protocol for clinical PGD procedure was established using 50 single cells in pre-clinical set-up. After whole genomic amplification by multiple displacement amplification with the DNA from single cells, three techniques were applied simultaneously to increase the accuracy and reliability of genetic diagnosis in single blastomere, including real-time PCR with Taq Man-MGB probe, haplotype analysis with polymorphic STR markers and Sanger sequencing. In the clinical PGD cycle, nine embryos at cleavage-stage were biopsied and subjected to genetic diagnosis. Two embryos diagnosed as free of TMEM67 mutation were transferred and one achieving normal pregnancy. Non-invasive prenatal assessment of trisomy 13, 18 and 21 by multiplex DNA sequencing at 18 weeks’ gestation excluded the aneuploidy of the analyzed chromosomes. A healthy boy was delivered by cesarean section at 39 weeks’ gestation. DNA sequencing from his cord blood confirmed the result of genetic analysis in the PGD cycle. The protocol developed in this study was proved to be rapid and safe for the detection of monogenic mutations in clinical PGD cycle. PMID:24039893

Cheng, Jing; Wang, Shufang; Ma, Minyue; Lu, Yu; Han, Dongyi; Yao, Yuanqing; Li, Yali; Yuan, Huijun



Improving clinical preimplantation genetic diagnosis for cystic fibrosis by duplex PCR using two polymorphic markers or one polymorphic marker in combination with the detection of the  F508 mutation  

Microsoft Academic Search

Cystic fibrosis (CF) is an autosomal recessive disease characterized by obstruction and chronic infection of the respiratory tract and pancreatic insufficiency. The first preimplantation genetic diagnosis (PGD) for CF was carried out in 1992. At our centre the first cycle was performed in 1993. However, the number of known CF mutations is >1000, so developing mutation-specific PCR protocols for PGD

V. Goossens; K. Sermon; W. Lissens; M. De Rycke; B. Saerens; A. De Vos; P. Henderix; H. Van de Velde; P. Platteau; A. Van Steirteghem; P. Devroey; I. Liebaers



ESHRE task force on ethics and Law22: preimplantation genetic diagnosis.  


This Task Force document discusses some relatively unexplored ethical issues involved in preimplantation genetic diagnosis (PGD). The document starts from the wide consensus that PGD is ethically acceptable if aimed at helping at-risk couples to avoid having a child with a serious disorder. However, if understood as a limit to acceptable indications for PGD, this 'medical model' may turn out too restrictive. The document discusses a range of possible requests for PGD that for different reasons fall outwith the accepted model and argues that instead of rejecting those requests out of hand, they need to be independently assessed in the light of ethical criteria. Whereas, for instance, there is no good reason for rejecting PGD in order to avoid health problems in a third generation (where the second generation would be healthy but faced with burdensome reproductive choices if wanting to have children), using PGD to make sure that one's child will have the same disorder or handicap as its parents, is ethically unacceptable. PMID:24927929

De Wert, G; Dondorp, W; Shenfield, F; Devroey, P; Tarlatzis, B; Barri, P; Diedrich, K; Provoost, V; Pennings, G



Moral attitudes and beliefs among couples pursuing PGD for sex selection.  


This article reports the results from a study of couples participating in a research protocol in which IVF/preimplantation genetic diagnosis (PGD) was available for non-medical sex selection. The study sought to characterize the moral attitudes and beliefs of couples actively pursuing IVF/PGD solely for purposes related to sex selection. Eighteen couples participated in ethnographic interviews from November 2005 to April 2006. These interviews explored couples' motivations for pursuing sex selection, moral beliefs and attitudes regarding sex selection and sources of moral ambivalence about the use of IVF/PGD for sex selection. Couples reported a combination of motivations for pursuing sex selection, including a desire to limit family size, concerns about parental age and financial concerns about multiple pregnancies. Many couples compared their decision to choices about abortion, maintaining that individuals have a right to make such decisions privately. Couples frequently expressed anxiety about telling their other children and family members about their plans to use IVF/PGD for sex selection. Few couples cited concerns about the physical or emotional burdens of IVF/PGD. The study's findings suggest that couples pursuing IVF/PGD for sex selection view this as an ethically complex decision and express considerable uncertainty about the ethical acceptability of this practice. PMID:21051290

Sharp, Richard R; McGowan, Michelle L; Verma, Jonathan A; Landy, David C; McAdoo, Sallie; Carson, Sandra A; Simpson, Joe Leigh; McCullough, Laurence B



Conceptualizing Couples' Decision Making in PGD: Emerging Cognitive, Emotional, and Moral Dimensions  

PubMed Central

Objective To illuminate and synthesize what is known about the underlying decision making processes surrounding couples’ preimplantation genetic diagnosis (PGD) use or disuse and to formulate an initial conceptual framework that can guide future research and practice. Methods This systematic review targeted empirical studies published in English from 1990 to 2008 that examined the decision making process of couples or individual partners that had used, were eligible for, or had contemplated PGD. Sixteen studies met the eligibility requirements. To provide a more comprehensive review, empirical studies that examined healthcare professionals’ perceptions of couples’ decision making surrounding PGD use and key publications from a variety of disciplines supplemented the analysis. Results The conceptual framework formulated from the review demonstrates that couples’ PGD decision making is composed of three iterative and dynamic dimensions: cognitive appraisals, emotional responses, and moral judgments. Conclusion Couples think critically about uncertain and probabilistic information, grapple with conflicting emotions and incorporate moral perspectives into their decision making about whether or not to use PGD. Practice Implications The quality of care and decisional support for couples who are contemplating PGD use can be improved by incorporating focused questions and discussion from each of the dimensions into counseling sessions. PMID:20060677

Hershberger, Patricia E.; Pierce, Penny F.



[Preimplantation diagnosis with HLA typing: birth of the first double hope child in France].  


Preimplantation genetic diagnosis (PGD) is authorized in France since 1999. After 10 years, technical results are encouraging. With the development of new technologies, our team is able to diagnosis the large majority of chromosome translocations and 75 monogenic diseases. However, PGD remains limited because of the growing augmentation of demands causing an increasing delay for the first procedure of more than 18 months. Since 2006, 19 couples asked for a PGD with HLA typing. In January 2011, 11 couples have already been included in our PGD program. The birth of the first child after PGD with HLA typing offers new perspectives of treatment for these couples. PMID:21944578

Lamazou, F; Steffann, J; Frydman, N; Burlet, P; Gigarel, N; Romana, S; Bonnefont, J-P; Lelorch, M; Hesters, L; Fanchin, R; Kerbrat, V; Vekemans, M; Munnich, A; Frydman, R



Preimplantation genetic diagnosis in female and male carriers of reciprocal translocations: clinical outcome until delivery of 312 cycles  

PubMed Central

Carriers of reciprocal translocations (rcp) are known to be at risk for reproductive difficulties. Preimplantation genetic diagnosis (PGD) is one of the options these carriers have to try in order to fulfil their desire to have a child. In the present study, we retrospectively looked at the results of 11 years (1997–2007) of PGD for rcp in our center to improve the reproductive counseling of these carriers. During this period 312 cycles were performed for 69 male and 73 female carriers. The mean female age was 32.8 years, the mean male age 35.8 years. Most carriers were diagnosed with a translocation because of fertility problems or recurrent miscarriages, and most of them opted for PGD to avoid these problems. In 150 of the 312 cycles, embryo transfer (ET) was feasible and 40 women had a successful singleton or twin pregnancy. This gives a live birth delivery rate of 12.8% per started cycle and of 26.7% per cycle with ET. Owing to the large number of abnormal embryos, PGD cycles for rcp often lead to cancellation of ET, explaining the low success rate when expressed per cycle with oocyte pick-up. Once ET was feasible, the live birth delivery rate was similar to that of PGD in general at our center. PGD is therefore an established option for specific reciprocal translocation carriers. PMID:22071893

Keymolen, Kathelijn; Staessen, Catherine; Verpoest, Willem; Liebaers, Inge; Bonduelle, Maryse



Detailed investigation of factors influencing amplification efficiency and allele drop-out in single cell PCR: implications for preimplantation genetic diagnosis  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) of single gene disorders relies on PCR-based tests performed on single cells (polar bod- ies or blastomeres). Despite the use of increasingly robust protocols, allele drop-out (ADO; the failure to amplify one of the two alleles in a heterozygous cell) remains a significant problem for diagnosis using single cell PCR. In extreme cases ADO can affect

Wirawit Piyamongkol; Mercedes G. Bermudez; Joyce C. Harper; Dagan Wells



Attitudes to reproductive genetic testing in women who had a positive BRCA test before having children: a qualitative analysis  

Microsoft Academic Search

The scope of conditions for which preimplantation genetic diagnosis (PGD) is licensed has recently been expanded in the United Kingdom to include genetic predisposition to adult-onset cancer. This qualitative interview study explores reproductive decision making, knowledge of and attitudes to reproductive genetic testing (prenatal diagnosis and PGD) with 25 women aged 18–45 years who received a positive BRCA test in

Elizabeth Ormondroyd; Louise Donnelly; Clare Moynihan; Cornelie Savona; Elizabeth Bancroft; D Gareth Evans; Rosalind Eeles; Stuart Lavery; Maggie Watson



Prevention of Lysosomal Storage Diseases and Derivation of Mutant Stem Cell Lines by Preimplantation Genetic Diagnosis  

PubMed Central

Preimplantation genetic diagnosis (PGD) allows birth of unaffected children for couples at risk for a genetic disorder. We present the strategy and outcome of PGD for four lysosomal storage disorders (LSD): Tay-Sachs disease (TSD), Gaucher disease (GD), Fabry disease (FD), and Hunter syndrome (HS), and subsequent development of stem cell lines. For each disease, we developed a family-specific fluorescent multiplex single-cell PCR protocol that included the familial mutation and informative markers surrounding the mutation. Embryo biopsy and PGD analysis were performed on either oocytes (polar bodies one and two) or on single blastomeres from a six-cell embryo. We treated twenty families carrying mutations in these lysosomal storage disorders, including 3 couples requiring simultaneous analysis for two disorders (TSD/GD, TSD/balanced Robertsonian translocation 45XYder(21;14), and HS/oculocutaneus albinism). These analyses led to an overall pregnancy rate/embryo transfer of 38% and the birth of 20 unaffected children from 17 families. We have found that PGD for lysosomal disorders is a safe and effective method to prevent birth of affected children. In addition, by using mutant embryos for the derivation of stem cell lines, we have successfully established GD and HS hESC lines for use as valuable models in LSD research. PMID:23320174

Altarescu, Gheona; Beeri, Rachel; Eiges, Rachel; Epsztejn-Litman, Silvina; Eldar-Geva, Talia; Elstein, Deborah; Zimran, Ari; Margalioth, Ehud J.; Levy-Lahad, Ephrat; Renbaum, Paul



Preimplantation genetic diagnosis for mitochondrial DNA disorders: ethical guidance for clinical practice  

PubMed Central

Although morally acceptable in theory, preimplantation genetic diagnosis (PGD) for mitochondrial DNA (mtDNA) disorders raises several ethical questions in clinical practice. This paper discusses the major conditions for good clinical practice. Our starting point is that PGD for mtDNA mutations should as far as possible be embedded in a scientific research protocol. For every clinical application of PGD for mtDNA disorders, it is not only important to avoid a ‘high risk of serious harm' to the future child, but also to consider to what extent it would be possible, desirable and proportional to try to reduce the health risks and minimize harm. The first issue we discuss is oocyte sampling, which may point out whether PGD is feasible for a specific couple. The second issue is whether one blastomere represents the genetic composition of the embryo as a whole – and how this could (or should) be investigated. The third issue regards the cutoff points below which embryos are considered to be eligible for transfer. We scrutinize how to determine these cutoff points and how to use these cutoff points in clinical practice – for example, when parents ask to take more or less risks. The fourth issue regards the number of cycles that can (or should) justifiably be carried out to find the best possible embryo. Fifth, we discuss whether follow-up studies should be conducted, particularly the genetic testing of children born after IVF/PGD. Finally, we offer the main information that is required to obtain a truly informed consent. PMID:19471315

Bredenoord, Annelien; Dondorp, Wybo; Pennings, Guido; de Die-Smulders, Christine; Smeets, Bert; de Wert, Guido



The first successful live birth following preimplantation genetic diagnosis using PCR for type 1 citrullinemia  

PubMed Central

Type 1 citrullinemia (CTLN1) is an autosomal recessive inherited metabolic disorder caused by anargininosuccinicnate synthetase deficiency. The patient was a 38-year-old Korean woman who is a carrier for CTLN1 and her first baby was diagnosed with CTLN1. Preimplantation genetic diagnosis (PGD) for CTLN1 in day 3 embryos using polymerase chain reaction was performed for live birth of healthy baby who is no affected with CTLN1. One unaffected blastocyst was transferred. This resulted in a clinical pregnancy and the live birth of healthy male twin. They were confirmed to be unaffected with CTNL1 by post natal diagnosis. This is the first case report of the use of PGD for CTNL1. PMID:24883299

Cho, Jae-Hyun; Lee, Kyung-Hee; Jeon, Il-Kyung; Kim, Jae-Min; Kang, Byung-Moon



The decision-making process of genetically at-risk couples considering preimplantation genetic diagnosis: initial findings from a grounded theory study.  


Exponential growth in genomics has led to public and private initiatives worldwide that have dramatically increased the number of procreative couples who are aware of their ability to transmit genetic disorders to their future children. Understanding how couples process the meaning of being genetically at-risk for their procreative life lags far behind the advances in genomic and reproductive sciences. Moreover, society, policy makers, and clinicians are not aware of the experiences and nuances involved when modern couples are faced with using Preimplantation Genetic Diagnosis (PGD). The purpose of this study was to discover the decision-making process of genetically at-risk couples as they decide whether to use PGD to prevent the transmission of known single-gene or sex-linked genetic disorders to their children. A qualitative, grounded theory design guided the study in which 22 couples (44 individual partners) from the USA, who were actively considering PGD, participated. Couples were recruited from June 2009 to May 2010 from the Internet and from a large PGD center and a patient newsletter. In-depth semi-structured interviews were completed with each individual partner within the couple dyad, separate from their respective partner. We discovered that couples move through four phases (Identify, Contemplate, Resolve, Engage) of a complex, dynamic, and iterative decision-making process where multiple, sequential decisions are made. In the Identify phase, couples acknowledge the meaning of their at-risk status. Parenthood and reproductive options are explored in the Contemplate phase, where 41% of couples remained for up to 36 months before moving into the Resolve phase. In Resolve, one of three decisions about PGD use is reached, including: Accepting, Declining, or Oscillating. Actualizing decisions occur in the Engage phase. Awareness of the decision-making process among genetically at-risk couples provides foundational work for understanding critical processes and aids in identifying important gaps for intervention and future research. PMID:22445765

Hershberger, Patricia E; Gallo, Agatha M; Kavanaugh, Karen; Olshansky, Ellen; Schwartz, Alan; Tur-Kaspa, Ilan



Preimplantation genetic diagnosis for gender selection in the United States  

SciTech Connect

Preimplantation genetic diagnosis (PGD) of gender selection for non medical reasons has been considered an unethical procedure by several authors and agencies in the Western society on the basis of disrupting the sex ratio, being discriminatory againsts women and disposal of normal embryos of the non desired gender. In this study, the analysis of a large series of PGD procedures for gender selection from a wide geographical area in the United States, shows that in general there is no deviation in preference towards any specific gender except for a preference of males in some ethnic populations of Chinese, Indian and Middle Eastern origin that represent a small percentage of the US population. In cases where only normal embryos of the non-desired gender are available, 45.5% of the couples elect to cancel the transfer, while 54.5% of them are open to have transferred embryos of the non-desired gender, this fact being strongly linked to cultural and ethnical background of the parents. In addition this study adds some evidence to the proposition that in couples with previous children of a given gender there is no biological predisposition towards producing embryos of that same gender. Based on these facts, it seems that objections to gender selection formulated by ethics committees and scientific societies are not well-founded.

Colls, P.; Silver, L.; Olivera, G.; Weier, J.; Escudero, T.; Goodall, N.; Tomkin, G.; Munne, S.



Strategies for prenatal and preimplantation genetic diagnosis in Marfan syndrome (MFS).  


Marfan syndrome (MFS) is an autosomal dominant disorder with a prevalence of 2-3 per 10 000 individuals. Symptoms range from skeletal overgrowth, cutaneous striae to ectopia lentis and aortic dilatation leading to dissection. Prenatal diagnosis was until recently mainly performed in familial cases by linkage analysis. However, mutation detection has become available with thorough screening methods. The phenotypic variability observed in MFS makes reproductive options difficult, as molecular diagnosis cannot predict clinical severity of the disease. Data are presented on 15 prenatal and/or preimplantation genetic diagnoses (PGD) in nine families, originating from Belgium, the Netherlands, Spain and France. In four families data from linkage analysis were used, whereas in five other families the causative FBN1 mutation was characterised. Four PGD cycles in two couples led to one ongoing pregnancy. In addition, two amniocenteses and nine chorionic villus (CV) samplings were performed. In five pregnancies an affected fetus was diagnosed. In one of them, the couple chose to continue the pregnancy and an affected child was born, whereas the other four couples decided to terminate the pregnancy. It is expected that the greater availability of mutation testing of the FBN1 gene will increase requests for prenatal diagnosis. PGD appears to be an acceptable alternative for couples facing ethical reproductive dilemmas. PMID:11810645

Loeys, B; Nuytinck, L; Van Acker, P; Walraedt, S; Bonduelle, M; Sermon, K; Hamel, B; Sanchez, A; Messiaen, L; De Paepe, A



Facilitating choice, framing choice: staff views on widening the scope of preimplantation genetic diagnosis in the UK.  


In the UK, the Human Fertilisation and Embryology Authority (HFEA) is responsible for licensing preimplantation genetic diagnosis (PGD). To date, licenses have been issued for the testing of about 70 genetic conditions, drawing on three key 'ethical principles'. Following a public consultation, the HFEA has recently widened the scope for PGD to include susceptibility to late onset, lower penetrance conditions such as inherited breast cancer. As the numbers and types of conditions which can potentially be tested for rises, the question of how, and indeed what limits should be set is timely. Drawing on qualitative interviews and ethics discussion groups which took place prior to or during the HFEA consultation, this paper explores the views of staff working in or linked to one PGD Unit in the UK, as to how they saw these potential changes. The paper thus provides an opportunity to develop greater understanding of how staff working in a morally contentious, innovative area viewed the potential expansion of their work, prior to that expansion taking place. Key themes include 'drawing lines' on behalf of others, particularly with the current emphasis on individual reproductive autonomy; and balancing the invasiveness and possible risks of PGD treatment against the 'seriousness' of the condition. More broadly, the paper highlights the complexities involved in trying to develop general 'ethical principles' to govern the use of ever evolving reproductive technologies. PMID:17573171

Williams, Clare; Ehrich, Kathryn; Farsides, Bobbie; Scott, Rosamund



Choosing embryos: ethical complexity and relational autonomy in staff accounts of PGD  

PubMed Central

The technique of preimplantation genetic diagnosis (PGD) is commonly explained as a way of checking the genes of embryos produced by IVF for serious genetic diseases. However, complex accounts of this technique emerged during ethics discussion groups held for PGD staff. These form part of a study exploring the social processes, meanings and institutions that frame and produce ‘ethical problems’ for practitioners, scientists and others working in the specialty of PGD in the UK. Two ‘grey areas’ raised by staff are discussed in terms of how far staff are, or in the future may be, able to support autonomous choices of women/couples: accepting ‘carrier’ embryos within the goal of creating a ‘healthy’ child; and sex selection of embryos for social reasons. These grey areas challenged the staff's resolve to offer individual informed choice, in the face of their awareness of possible collective social effects that might ensue from individual choices. We therefore argue that these new forms of choice pose a challenge to conventional models of individual autonomy used in UK genetic and reproductive counselling, and that ‘relational autonomy’ may be a more suitable ethical model to describe the ethical principles being drawn on by staff working in this area. PMID:18092985

Ehrich, Kathryn; Williams, Clare; Farsides, Bobbie; Sandall, Jane; Scott, Rosamund



Preimplantation genetic diagnosis: its role in prevention of deafness.  


Deafness is a global problem. In India deafness ranges from 4 % in urban to 11 % in rural and slum areas, out of which 50 % is conductive hearing loss hence curable. Genetic transmission accounts for 50 % of the cases of congenital deafness, and of these, around 30 % are syndromic and 70 % are non-syndromic. Genetic counseling is going to make aware the parents of all appropriate treatments. Preimplantation genetic diagnosis can help to have a baby free from genetic deafness. Procedure is almost safe, harmless, non-invasive and ethically acceptable. While Amniocentesis is a non-invasive method, prenatal genetic testing through Chorionic villous sampling is invasive. The connexin 26 (CX26W 24X) mutations are the most common cause of non-syndromic hearing loss and easy to identify by polymerase chain reaction. There is always co-morbidity after cochlear implantation and the person remains handicapped while baby after PGD shall be having healthy normal life and person prone to environmental factors may be counseled and guided to prevent deafness in next generation. Public must be made aware of noise pollution, tobacco toxicity and consanguinity. The Obstetrician and Pediatrician apart from ENT surgeon should be involved to prevent antenatal or neonatal deafness. PMID:24605291

Taneja, M K



Evolution of a genetic diagnosis.  


Understanding the relationship between genotype and phenotype has become an integral part of the diagnosis and management of patients with inherited arrhythmias and cardiomyopathies. Given the existence of background noise, the majority of genetic testing results should be incorporated into clinical decision making as probabilistic, rather than deterministic, in the diagnosis and management of inherited arrhythmias. This case report captures multiple snapshots of clinical care in the evolution of a diagnosis of a single patient, highlighting the need for repeated phenotypic and genotypic assessment for both the patient and their family. PMID:24237251

Laksman, Z; Dulay, D; Gollob, M H; Skanes, A C; Krahn, A D



Ethics of PGD: thoughts on the consequences of typing HLA in embryos.  


As with so many fields of study associated with assisted human reproduction, many ethical issues are raised by the practice of preimplantation diagnosis of inherited disease (PGD). Some are part and parcel of assisted conception, e.g.the rights of human embryos in vitro and of embryologists to establish them, carry out research and discard them. Others unique to clinical PGD were discussed at an earlier meeting on PGD (Edwards et al., 2003). Recent developments in PGD are discussed briefly in this Commentary, especially the ethics of designer babies. PMID:15333255

Edwards, R G



Ethics of PGD: thoughts on the consequences of typing HLA in embryos  

Microsoft Academic Search

As with so many fields of study associated with assisted human reproduction, many ethical issues are raised by the practice of preimplantation diagnosis of inherited disease (PGD). Some are part and parcel of assisted conception, e.g. the rights of human embryos in vitro and of embryologists to establish them, carry out research and discard them. Others unique to clinical PGD

RG Edwards



Ovarian reserve and PGD treatment outcome in women with myotonic dystrophy.  


Myotonic dystrophy (DM) is the most common form of muscular dystrophy in adults. There are conflicting reports about its effect on female fertility. This study investigated ovarian reserve and IVF-preimplantation genetic diagnosis (PGD) outcome in women with DM1. A total of 21 women undergoing PGD for DM1 were compared with 21 age- and body mass index-matched women undergoing PGD for other diseases. Ovarian reserve markers, response to stimulation, embryo quality and clinical pregnancy and live birth rates were compared. Day-3 FSH concentration was higher, while anti-Müllerian hormone concentration and antral follicle count were lower in the DM1 group (median, range: 6.9 (1.8-11.3) versus 5.7 (1.5-10.7)IU/l; 0.9 (0.17-5.96) versus 2.68 (0.5-9.1)ng/ml; and 13 (0-63) versus 23 (8-40) follicles, respectively, all P < 0.05). Total FSH dose was higher (5200 versus 2250 IU, P = 0.004), while the numbers of oocytes retrieved (10 versus 16, P < 0.04) and metaphase-II oocytes (9 versus 12, P < 0.03) were lower in the DM1 group. The number of cycles with top-quality embryos and the clinical pregnancy rate were lower in the DM1 group. In conclusion, there is evidence of diminished ovarian reserve and less favourable IVF-PGD outcome in women with DM1. Myotonic Dystrophy (DM) is the most common form of muscular dystrophy in adults. There is evidence of subfertility in males affected with the disease but conflicting reports about the effect of the disease on female fertility. The aim of our study was to investigate ovarian reserve and IVF-PGD results in women with DM. Twenty-one women undergoing preimplantation genetic diagnosis (PGD) treatment for DM were compared to 21 age- and BMI matched women undergoing PGD treatment for other diseases. The two groups were compared for antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) levels (the best known markers of ovarian reserve and fertility potential), ovarian response, embryo quality and pregnancy and live birth rates. AFC and the AMH levels were statistically significant lower in the DM group. Total medication dose needed for ovarian stimulation was higher, the number of oocytes and mature oocytes retrieved, and the number of cycles with top quality embryos were lower in the DM group compared to the controls. In conclusion, there is evidence of diminished ovarian reserve, and less favorable IVF-PGD outcome in women with DM. Therefore, we recommend advising these women about the possibility of early decreasing ovarian function in order to prevent any delay in reproductive planning. PMID:24813161

Srebnik, N; Margalioth, E J; Rabinowitz, R; Varshaver, I; Altarescu, G; Renbaum, P; Levi-Lahad, E; Weintraub, A; Eldar-Geva, T



Accreditation of the PGD laboratory.  


Accreditation according to an internationally recognized standard is increasingly acknowledged as the single most effective route to comprehensive laboratory quality assurance, and many countries are progressively moving towards compulsory accreditation of medical testing laboratories. The ESHRE PGD Consortium and some regulatory bodies recommend that all PGD laboratories should be accredited or working actively towards accreditation, according to the internationally recognized standard ISO 15189, 'Medical laboratories-Particular requirements for quality and competence'. ISO 15189 requires comprehensive quality assurance. Detailed management and technical requirements are defined in the two major chapters. The management requirements address quality management including the quality policy and manual, document control, non-conformities and corrective actions, continual improvement, auditing, management review, contracts, referrals and resolution of complaints. Technical requirements include personnel competence (both technical and medical), equipment, accommodation and environment, and pre-analytical, analytical and post-analytical processes. Emphasis is placed on the particular requirements of patient care: notably sample identification and traceability, test validation and interpretation and reporting of results. Quality indicators must be developed to monitor contributions to patient care and continual improvement. We discuss the implementation of ISO 15189 with a specific emphasis on the PGD laboratory, highlight elements of particular importance or difficulty and provide suggestions of effective and efficient ways to obtain accreditation. The focus is on the European environment although the principles are globally applicable. PMID:20097923

Harper, J C; Sengupta, S; Vesela, K; Thornhill, A; Dequeker, E; Coonen, E; Morris, M A



Outcomes of ovarian stimulation in a two-day oocyte collection week with PGD cycles compared to a five-day oocyte collection week with conventional IVF/ICSI cycles.  


We assessed the outcomes of ovarian stimulation in a two-day egg collection (EC) week with preimplantation genetic diagnosis (PGD) cycles (N?=?307) compared to a five-day EC week with conventional in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles (N?=?2,417). The mean (SD) age of women undergoing PGD was 34 (3.97) and 35 (3.85) for IVF/ICSI (P < 0.001), the number of oocytes collected was 13 (7.37) and 11 (7.02), (P < 0.001), while the mean (SD) number of fertilized oocytes was 8 (5.09) and 6 (4.58), respectively (P < 0.001). The clinical pregnancy rate per embryo transfer (ET) was 37% with PGD and 38% with IVF/ICSI (P?=?0.49), while the implantation rate was 0.35 and 0.30, respectively (P?=?0.05). After adjusting for age and confounding variables including the number of oocytes collected and fertilized normally, the mode of treatment (PGD or IVF/ICSI) had no effect on clinical pregnancy (P?=?0.48). In conclusion, scheduling of PGD cycles to a two-day EC week did not compromise the outcomes of ovarian stimulation when compared to a five-day EC week with conventional IVF/ICSI cycles. This can allow the provision of a more patient friendly service, increase the flexibility of satellite PGD services, and facilitate cycle programming with the genetics team providing PGD. PMID:22050306

Hamoda, H; Pepas, L; Freed, C; Grace, J; Khalaf, Y; Braude, P; El-Toukhy, T



Diagnosis and new treatments in genetic neuropathies  

Microsoft Academic Search

The genetic neuropathies are a clinically and genetically heterogeneous group of diseases of which the most common types are Charcot–Marie–Tooth disease (CMT), the hereditary sensory and autonomic neuropathies and the distal hereditary motor neuropathies. More than 30 causative genes have been described, making an accurate genetic diagnosis increasingly possible. Although no specific therapies are yet available, research into their pathogenesis

M M Reilly; M E Shy



The embryo as moral work object: PGD/IVF staff views and experiences  

PubMed Central

We report on one aspect of a study that explored the views and experiences of practitioners and scientists on social, ethical and clinical dilemmas encountered when working in the field of preimplantation genetic diagnosis (PGD) for serious genetic disorders. The study produced an ethnography based on observation, interviews and ethics discussion groups with staff from two PGD/IVF Units in the UK. We focus here on staff perceptions of work with embryos that entails disposing of ‘affected’ or ‘spare’ embryos or using them for research. A variety of views were expressed on the ‘embryo question’ in contrast to polarised media debates. We argue that the prevailing policy acceptance of destroying affected embryos, and allowing research on embryos up to 14 days leaves some staff with rarely reported, ambivalent feelings. Staff views are under-researched in this area and we focus on how they may reconcile their personal moral views with the ethical framework in their field. Staff construct embryos in a variety of ways as ‘moral work objects’. This allows them to shift attention between micro-level and overarching institutional work goals, building on Casper's concept of ‘work objects’ and focusing on negotiation of the social order in a morally contested field. PMID:18444955

Ehrich, Kathryn; Williams, Clare; Farsides, Bobbie



Preimplantation genetic diagnosis and the 'new' eugenics  

Microsoft Academic Search

Preimplantation genetic diagnosis (PID) is often seen as an improvement upon prenatal testing. I argue that PID may exacerbate the eugenic features of prenatal testing and make possible an expanded form of free-market eugenics. The current practice of prenatal testing is eugenic in that its aim is to reduce the numbers of people with genetic disorders. Due to social pressures

D S King



Diagnosis and new treatments in genetic neuropathies.  


The genetic neuropathies are a clinically and genetically heterogeneous group of diseases of which the most common types are Charcot-Marie-Tooth disease (CMT), the hereditary sensory and autonomic neuropathies and the distal hereditary motor neuropathies. More than 30 causative genes have been described, making an accurate genetic diagnosis increasingly possible. Although no specific therapies are yet available, research into their pathogenesis has revolutionised our understanding of the peripheral nervous system and allowed the development of rational approaches to therapy. The first therapeutic trials in CMT are currently underway. This review will suggest an approach to the diagnosis of these disorders and provide an update on new therapies. PMID:19917815

Reilly, M M; Shy, M E



[Genetic diagnosis of phaeochromocytomas and paragangliomas].  


Up to 30% of phaeochromocytomas and paragangliomas occur in the context of inherited tumor syndromes. Familial history and clinical presentation have to be strongly detailed to guide genetic testing. The identification of a genetic predisposition in a patient with phaeochromocytoma or paraganglioma has a positive impact in terms of medical care and follow-up for the proband and allows genetic testing in apparently asymptomatic family members. Two clusters of genes are described depending on their implication in the pathogenesis of inherited tumors. An algorithm for the genetic diagnosis of phaeochromocytomas and paragangliomas is proposed by The French network of oncogenetic laboratories. These recommendations will probably change with the identification of new predisposition genes and the development of new sequencing technologies.Genetic testing is prescribed by a specialist, as part of a cancer genetics specialist consultation in endocrine tumors. The psychological support is essential throughout the family survey. PMID:24612707

Cardot-Bauters, Catherine; Ainaouï, Malika; Coppin, Lucie; Pigny, Pascal



Diagnosis: genetic testing cannot stand alone.  


Genetic testing uses advanced laboratory techniques to identify protein alterations, certain metabolites, chromosomes, or nucleic acids by which a genotype is determined or inferred. These tests provide insights into the molecular basis and physiopathology of genetic diseases, information which is critical for prevention, treatment and genetic counseling. Initiated in 1982, Cuba's National Program for Diagnosis, Management and Prevention of Birth Defects and Hereditary Diseases ensures availability of genetic tests to all Cubans who need them, free of charge, assisting physician-patient decisions. The tests may be used to confirm diagnoses, point to hereditary diseases and potential congenital problems during pregnancy or in pre-symptomatic stages, and diagnose carriers of recessive diseases. PMID:25208125

Morales-Peralta, Estela



[Update on preimplantation genetic diagnosis and screening].  


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. PMID:25161052

K?rösi, Tamás; Török, Olga; Vajta, Gábor



Autonomy and freedom of choice in prenatal genetic diagnosis  

Microsoft Academic Search

An increase in autonomy and freedom is often considered one ofthe main arguments in favour of a broad use of genetic testing.Starting from Gerald Dworkin's reflections on autonomy and choicethis article examines some of the implications which accompanythe increase in choices offered by prenatal genetic diagnosis.Although personal autonomy and individual choice are importantaspects in the legitimation of prenatal genetic diagnosis,

Elisabeth Hildt



Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management.  


Hyperinsulinaemic hypoglycaemia (HH) is due to the unregulated secretion of insulin from pancreatic ?-cells. A rapid diagnosis and appropriate management of these patients is essential to prevent the potentially associated complications like epilepsy, cerebral palsy and neurological impairment. The molecular basis of HH involves defects in key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and UCP2) which regulate insulin secretion. The most severe forms of HH are due to loss of function mutations in ABCC8/KCNJ11 which encode the SUR1 and KIR6.2 components respectively of the pancreatic ?-cell K(ATP) channel. At a histological level there are two major forms (diffuse and focal) each with a different genetic aetiology. The diffuse form is inherited in an autosomal recessive (or dominant) manner whereas the focal form is sporadic in inheritance and is localised to a small region of the pancreas. The focal form can now be accurately localised pre-operatively using a specialised positron emission tomography scan with the isotope Fluroine-18L-3, 4-dihydroxyphenyalanine (18F-DOPA-PET). Focal lesionectomy can provide cure from the hypoglycaemia. However the diffuse form is managed medically or by near total pancreatectomy (with high risk of diabetes mellitus). Recent advances in molecular genetics, imaging with 18F-DOPA-PET/CT and novel surgical techniques have changed the clinical approach to patients with HH. PMID:22231386

Senniappan, Senthil; Shanti, Balasubramaniam; James, Chela; Hussain, Khalid



Critical Issues for Dentistry: PGD Program Directors Respond  

Microsoft Academic Search

Discussion of critical issues facing postgraduate education in general dentistry (PGD) and dental education in general has been intense in the past decade. This study reports on critical issues raised by directors of PGD programs that may help direct future research and action within dental education and the larger profession. The analysis reports responses to an open-ended question sent to

Kathryn A. Atchison; Susan E. Cheffetz


[Genetic structure of the Mongols as derived from the ABO, MN, Rh, EsD, GLO1, PGM1, AcP, 6-PGD, Hp, Gc, Tf, C'3 and ChE2 loci].  


According to integral characterization of gene frequencies of the investigated loci AB0, MN, Rh, GLO1, PGM1, EsD, AcP, 6-PGD, Hp, Tf, Gc, C'3 and ChE2, Mongolian population has high level of polymorphism, with the exception of haplotypes R" (cdE) and Ry(CdE) at the Rh locus and TfB0-1 at the Tf locus. The data on biochemical and immunological polymorphic gene markers analysed in the population of Mongolia show that the Mongolians have some distinctive features, in comparison with the mean-in-the-world characteristics: high frequencies of the B genes at the AB0 locus; D, E, R1 and R2 at the Rh locus; GLO11, PGDc, TfDChi, E2(C5+), PGM1(1+); low frequencies of the genes A(AB0), R0(Rh), AcPc, Hp1, Gc2, C'3F, PGM 1(2-); the rest of the genes at the above-mentioned loci and the genes of the locus MN have the mean-in-the-world frequencies. PMID:1908400

Vatsuur', Zh; Samvuugi?n, N; Shne?der, Iu V; Petrishchev, V N; Rychkov, Iu G



The challenges and surprises of a definitive molecular genetic diagnosis.  


Making precise molecular genetic diagnoses in inherited kidney diseases is important. Gee et al. describe families with end-stage renal disease secondary to a presumed diagnosis of a nephronophthisis-related ciliopathy (NPHP-RC), in whom a combination of approaches allowed genetic diagnoses to be made. New genetic approaches to the diagnosis of childhood renal failure are becoming mainstream and will hopefully improve patient management, avoid clinical misdiagnoses, reduce the need for invasive investigations, and allow screening of at-risk relatives. PMID:24682124

Sayer, John A; Simms, Roslyn J



New molecular genetic tests in the diagnosis of heart disease.  


With the increasing use of next-generation sequencing applications, there has been an increase in identification of genetic causes of cardiac disease. This technology has also enabled the transition of these genes into the clinical setting and the rapid growth of large gene tests for the diagnosis of heart disorders. The ability to combine tests to include similar, but distinct, diseases has shown that many genes can be responsible for a wide variety of both syndromic and nonsyndromic disorders. This article discusses the current state of molecular genetic diagnosis for cardiac disorders, focusing on diseases with mendelian inheritance. PMID:24507793

Lebo, Matthew S; Baxter, Samantha M



Infertile couples with Robertsonian translocations: preimplantation genetic analysis of embryos reveals chaotic cleavage divisions  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) may provide a feasible option for some Robertsonian translocation carriers who experience\\u000a severe difficulty in achieving a normal pregnancy. We report on five PGD cycles for two such couples, 45,XY,der(13;14)(q10:q10)\\u000a and 45,XX,der(13;21)(q10;q10), carried out by biopsy of two cells from day 3 post-insemination embryos generated by in vitro\\u000a fertilisation. Locus-specific YAC probes for chromosomes 13, 14

Clare M. Conn; Joyce C. Harper; Robert M. L. Winston; Joy D. A. Delhanty



Genetic testing and early diagnosis and intervention: boon or burden?  

PubMed Central

The possibility of early diagnosis and intervention is radically changed by the advent of genetic testing. The recent report of the Nuffield Council on Bioethics is timely and helpful. I have suggested, that not only the severity of the disability indicated by genetic information, and the accuracy of the data, ought to govern the approach to the implementation of screening for genetic disorders. In addition, assessment of the value of the information to those involved should be considered. The efficacy of the available therapeutic measures, combined with the prognostic data are important indices of the value of the information. These measures fall into three categories and thus indicate that three different courses of intervention may be appropriate. Three approaches to diagnosis and intervention are then outlined, drawing on the experience of various clinical initiatives. PMID:8731537

Hepburn, E R



Genetics and diagnosis of central diabetes insipidus.  


Most of the central diabetes insipidus cases seen in general practice are acquired but the rare cases of hereditary autosomal dominant or recessive neurohypophyseal diabetes insipidus have provided further cellular understanding of the mechanisms responsible for pre-hormone folding, maturation and release. Autosomal dominant central diabetes insipidus is secondary to the toxic accumulation of vasopressin mutants as fibrillar aggregates in the endoplasmic reticulum of hypothalamic magnocellular neurons producing vasopressin. As well, Trpv1(-/-) and Trpv4(-/-) mice have shed new light on the perception of tonicity through the stretch receptors TRPVs expressed both in central and peripheral neurons. The genomic information provided by sequencing the AVP gene is key to the routine care of these patients and, as in other genetic diseases, reduces health costs and provides psychological benefits to patients and families. In addition, simple, inexpensive blood and urine measurements together with clinical characteristics and brain magnetic resonance imaging (MRI) could distinguish between central, nephrogenic and polydipsic cases. PMID:22520736

Bichet, Daniel G



Hyperinsulinaemic Hypoglycaemia: Genetic Mechanisms, Diagnosis and Management  

PubMed Central

Hyperinsulinaemic hypoglycaemia (HH) is characterized by unregulated insulin secretion from pancreatic ?-cells. Untreated hypoglycaemia in infants can lead to seizures, developmental delay, and subsequent permanent brain injury. Early identification and meticulous managementof these patients is vital to prevent neurological insult. Mutations in eight different genes (ABCC8, KCNJ11, GLUD1, CGK, HADH, SLC16A1, HNF4A and UCP2) have been identified to date in patients with congenital forms of hyperinsulinism (CHI). The most severe forms of CHI are due to mutations in ABCC8 and KCJN11, which encode the two components of pancreatic ?-cell ATP-sensitive potassium channel. Recent advancement in understanding the genetic aetiology, histological characterisation into focal and diffuse variety combined with improved imaging (such as fluorine 18 L-3, 4-dihydroxyphenylalanine positron emission tomography 18F-DOPA-PET scanning) and laparoscopic surgical techniques have greatly improved management. In adults, HH can be due to an insulinoma, pancreatogenous hypoglycaemic syndrome, post gastric-bypass surgery for morbid obesity as well as to mutations in insulin receptor gene. This review provides an overview of the molecular basis of CHI and outlines the clinical presentation, diagnostic criteria, and management of these patients. Conflict of interest:None declared. PMID:23032149

Mohamed, Zainaba; Arya, Ved Bhushan; Hussain, Khalid



Support vector machine-based image classification for genetic syndrome diagnosis  

E-print Network

Support vector machine-based image classification for genetic syndrome diagnosis Amit David, Boaz-based image classifiers, thereby enabling the diagnosis of genetic abnormalities. By thresholding the distance-of-the-art classifiers demonstrates the benefit of SVM-based genetic syndrome diagnosis. Ã? 2004 Elsevier B.V. All rights

Lerner, Boaz


PGD2-CRTH2 pathway promotes tubulointerstitial fibrosis.  


Urinary excretion of lipocalin-type PGD(2) synthase (L-PGDS), which converts PG H(2) to PGD(2), increases in early diabetic nephropathy. In addition, L-PGDS expression in the tubular epithelium increases in adriamycin-induced nephropathy, suggesting that locally produced L-PGDS may promote the development of CKD. In this study, we found that L-PGDS-derived PGD(2) contributes to the progression of renal fibrosis via CRTH2-mediated activation of Th2 lymphocytes. In a mouse model, the tubular epithelium synthesized L-PGDS de novo after unilateral ureteral obstruction (UUO). L-PGDS-knockout mice and CRTH2-knockout mice both exhibited less renal fibrosis, reduced infiltration of Th2 lymphocytes into the cortex, and decreased production of the Th2 cytokines IL-4 and IL-13. Furthermore, oral administration of a CRTH2 antagonist, beginning 3 days after UUO, suppressed the progression of renal fibrosis. Ablation of IL-4 and IL-13 also ameliorated renal fibrosis in the UUO kidney. Taken together, these data suggest that blocking the activation of CRTH2 by PGD(2) might be a strategy to slow the progression of renal fibrosis in CKD. PMID:22997255

Ito, Hideyuki; Yan, Xiaoxiang; Nagata, Nanae; Aritake, Kosuke; Katsumata, Yoshinori; Matsuhashi, Tomohiro; Nakamura, Masataka; Hirai, Hiroyuki; Urade, Yoshihiro; Asano, Koichiro; Kubo, Masato; Utsunomiya, Yasunori; Hosoya, Tatsuo; Fukuda, Keiichi; Sano, Motoaki



Attitudes toward genetic testing in childhood and reproductive decision-making for familial adenomatous polyposis  

PubMed Central

Childhood DNA testing, prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) are available for familial adenomatous polyposis (FAP). However, the use of PND and PGD is controversial. The purpose of this study was to investigate attitudes toward, and experiences with, childhood DNA testing, PND and PGD among members of families at high risk for FAP. In this nationwide, cross-sectional study, questionnaires were sent to individuals from families at high risk for FAP assessing attitudes toward and experiences with childhood testing, PND and PGD, as well as several sociodemographic, clinical and psychosocial variables. Of the individuals from FAP families invited to participate in the study, 525 members participated (response rate=64%). Most parents who had children who were minors (n=93) (82%) were satisfied with the DNA testing procedure. One-third of all individuals wanted DNA testing for their children before age 12. Forty percent of FAP patients indicated that the disease influenced their desire to have children. Only 15% considered termination of pregnancy for FAP acceptable. Approximately 30% of individuals with a FAP diagnosis and their partners considered PND and PGD as acceptable for themselves. A positive attitude was associated with higher levels of guilt and a positive attitude toward termination of pregnancy. Importantly, of those with FAP at childbearing age, 84% had had no previous information at all about either PND or PGD. Future efforts should be aimed at educating FAP family members about reproductive options, allowing them to make an informed choice about family planning. Routine discussion of all reproductive options with a medical specialist should be encouraged. PMID:19809485

Douma, Kirsten F L; Aaronson, Neil K; Vasen, Hans F A; Verhoef, Senno; Gundy, Chad M; Bleiker, Eveline M A



Genetic imprecision: Diagnosis of possible defects often cannot predict prognosis  

SciTech Connect

The author discusses the difficulties in using current genetic information for the detection of hereditary diseases. Although there have been many advances in cytogenetic and molecular testing, the diagnosis of defects does not necessarily predict prognosis. Detection of mutant alleles, mosaicism, familial chromosomal rearrangements and de novo chromosomal rearrangements lends uncertainties to genetic counselling. The problems have been compounded by a lack of follow-up to determine if a defect actually exists in a fetus aborted as a result of counselling; nor has there been long-term follow-up of fetuses carried to term that appear healthy at birth. Disappointments after the discovery of the cystic fibrosis gene were due to discovery of many mutations of the gene, making screening for the disease difficult. Some genetic counselors question the benefits of screening for this disease since with advances in treatment, life span has been lengthened and quality of life has been improved.

Lewis, R.



High volume molecular genetic identification of single nucleotide polymorphisms using Genetic Bit Analysis Application to human genetic diagnosis  

SciTech Connect

The most common type of genetic disease-associated mutation is the single nucleotide polymorphism (SNP). Because most genetic diseases can be caused by multiple SNPs in the same gene, effective routine diagnosis of complex genetic diseases is dependent on a simple and reliable method of interrogating SNP sites. Molecular Tool`s solid phase assay capable of direct genotyping (single base sequencing) of SNP sites, Genetic Bit Analysis (GBA), involves hybridization-capture of a single-stranded PCR product to a sequence-specific, microtiter plate-bound oligonucleotide primer. The captured PCR product then acts as template for single-base extension of the capture primer across the polymorphic site, enabling direct determination of the base composition of the polymorphism through a simple colormetric assay. Genotyping in a high volume, semi-automated, processing system with a current capacity of 100 SNP interrogations per technician per day enables the screening of candidate mutations rapidly and cost-effectively, critically important to comprehensive genetic diagnosis. Using this gel-free technology, we have developed prototype diagnostic tests for CFTR and ApoE polymorphisms which enable direct sequencing of the polymorphic base at each site of interest. Routine clinical diagnosis of genetically complex diseases such as cystic fibrosis is dependent on this combination of robust biochemistry and simple format. Additionally, the ability to transfer the format and biochemistry to any disease gene of interest enables the broad application of this technology to clinical diagnostics, especially for genetically complex diseases.

Boyce-Jacino, M.T.; Reynolds, J.; Nikiforov, T. [Molecular Tool, Inc., Baltimore, MD (United States)] [and others



Rapid molecular genetic diagnosis of hypertrophic cardiomyopathy by semiconductor sequencing  

PubMed Central

Background Rapidly determining the complex genetic basis of Hypertrophic cardiomyopathy (HCM) is vital to better understanding and optimally managing this common polygenetic cardiovascular disease. Methods A rapid custom Ion-amplicon-resequencing assay, covering 30 commonly affected genes of HCM, was developed and validated in 120 unrelated patients with HCM to facilitate genetic diagnosis of this disease. With this HCM-specific panel and only 20 ng of input genomic DNA, physicians can, for the first time, go from blood samples to variants within a single day. Results On average, this approach gained 595628 mapped reads per sample, 95.51% reads on target (64.06 kb), 490-fold base coverage depth and 93.24% uniformity of base coverage in CDS regions of the 30 HCM genes. After validation, we detected underlying pathogenic variants in 87% (104 of 120) samples. Tested seven randomly selected HCM genes in eight samples by Sanger sequencing, the sensitivity and false-positive-rate of this HCM panel was 100% and 5%, respectively. Conclusions This Ion amplicon HCM resequencing assay provides a currently most rapid, comprehensive, cost-effective and reliable measure for genetic diagnosis of HCM in routinely obtained samples. PMID:24938736



PGD for dystrophin gene deletions using fluorescence in situ hybridization  

Microsoft Academic Search

Duchenne muscular dystrophy and Becker muscular dystrophy (DMD and BMD) are caused by mutations in the dystrophin gene (Xp21). In two-thirds of DMD\\/BMD cases, the mutation is a large deletion of one or several exons. We have established PGD for DMD\\/BMD using interphase fluorescence in situ hybridization (FISH) analysis on single nuclei from blastomeres for the detection of deletions of

H. Malmgren; I. White; S. Johansson; L. Levkov; E. Iwarsson; M. Fridström; Elisabeth Blennow



Successful application of preimplantation genetic diagnosis for hypokalaemic periodic paralysis.  


Hypokalaemic periodic paralysis is a rare dominant inherited disease where a person suffers sudden falls of circulating potassium concentrations, producing muscle weakness and sometimes severe paralysis. Attacks can occur as frequently as several times a day or once in a year. The age of onset is usually adolescence but symptoms can appear as early as 10 years of age. Muscle weakness can compromise vital functions such as breathing or swallowing and heart arrhythmias are also frequent during attacks. Preimplantation genetic diagnosis, an early form of prenatal diagnosis for couples at risk of transmitting inherited diseases, was used to prevent the transmission of this disease. Six polymorphic short tandem repeat or microsatellite markers (STR) closely linked to the CACNA1S gene were tested. Three fully informative markers were chosen to establish the disease-bearing haplotype in the family and to determine the genetic status of five embryos by multiplex fluorescent heminested PCR. Four of the five embryos tested were diagnosed as non-affected and one as affected. Two embryos were transferred resulting in a singleton pregnancy and the birth of a healthy girl. PMID:20541469

Alberola, Trinitat M; Vendrell, Xavier; Bautista-Llácer, Rosa; Vila, Maria; Calatayud, Carmen; Pérez-Alonso, Manuel



[Contribution of genetics to pathogenicity and diagnosis of Marfan syndrome].  


The anatomical substrate of Marfan's syndrome is a degeneration of elastic fibres and disorganization of the collagen. It is now known that these lesions are due to mutation of genes localised on chromosome 15. The first of them (FBN1) codes for the main constitutive protein of the elastic tissue: fibrillin 1, present mainly in structures which must resist load and stress (aortic adventitia, the suspending ligament of the lens, skin); the second (FBN2) codes for fibrillin 2: responsible for the orientation of the elastin and mainly present in cartilage, the aortic media, the bronchi, and all tissues rich in elastin. Mutations of FBN1 are very common and are associated not only with Marfan's syndrome but also fibrillinopathies: incomplete forms, neonatal forms, ectopic lens, isolated aneurysms of the thoracic aorta. The widespread distribution of fibrillin explains the pleiotropic nature of Marfan's syndrome and its clinical presentation. The variability of interfamilial expression is due to genetic heterogeneity (at least two genes) and alletic differences (different mutations of FBN1 from one family to another), also explaining mild forms due to quantitative reduction in normal fibrillin and severe forms by "negative dominance" where the fibrillin is structurally abnormal because of alteration of the polymerisation mechanism. The biologic diagnosis of fibrillopathy can be made by a protein test analysing fibrillin on a culture of the patient's fibroblast obtained by skin biopsy. At present, molecular diagnosis of the mutation within the FBN1 gene is not feasible as a routine procedure. PMID:9587455

Boileau, C; Collod, G; Bonnet, D



'My funky genetics’: BRCA1/2 mutation carriers' understanding of genetic inheritance and reproductive merger in the context of new repro-genetic technologies  

PubMed Central

INTRODUCTION Deleterious mutations in the BRCA1/BRCA2 genes elevate lifetime risk of breast and ovarian cancer. Each child of a mutation-positive parent has a 50% chance of inheriting it. Pre-implantation genetic diagnosis (PGD) permits prospective parents to avoid transmitting a BRCA1/2 mutation to a child, introducing predictability into a process historically defined by chance. This investigation explored how BRCA1/2 mutation carriers understand genetic inheritance and consider a child’s inheritance of a BRCA1/2 mutation, given the opportunities that exist to pursue PGD. METHOD 39 female and male BRCA1/2 mutation carriers of reproductive age were recruited from urban cancer and reproductive medical centers. Participants completed a standardized educational presentation on PGD and prenatal diagnosis, with pre- and post-test assessments. An interdisciplinary team of qualitative researchers analyzed data using grounded theory techniques. FINDINGS Participants expressed the belief that reproduction yields children with unique genetic strengths and challenges, including the BRCA1/2 mutation, family traits for which predictive tests do not exist, and hypothetical genetic risks. Participants expressed preference for biologically-related children, yet stated their genetically ‘well’ partner’s lineage would be marred through reproductive merger, requiring the well partner to assume the burden of the BRCA1/2 mutation via their children. Participants expressed diverse views of genetically ‘well’ partners’ participation in family planning and risk management decisions. DISCUSSION Pressure to use reprogenetic technology may grow as genetic susceptibility testing becomes more widely available. Work with individuals and couples across the disease spectrum must be attuned to they ways beliefs about genetic inheritance play into reproductive decision making. PMID:22709328

Rubin, Lisa R.; Doyle, Maya; Stern, Rikki; Savin, Katie; Hurley, Karen; Sagi, Michal



From brute luck to option luck? On genetics, justice, and moral responsibility in reproduction.  


The structure of our ethical experience depends, crucially, on a fundamental distinction between what we are responsible for doing or deciding and what is given to us. As such, the boundary between chance and choice is the spine of our conventional morality, and any serious shift in that boundary is thoroughly dislocating. Against this background, I analyze the way in which techniques of prenatal genetic diagnosis (PGD) pose such a fundamental challenge to our conventional ideas of justice and moral responsibility. After a short description of the situation, I first examine the influential luck egalitarian theory of justice, which is based on the distinction between choice and luck or, more specifically, between option luck and brute luck, and the way in which it would approach PGD (section II), followed by an analysis of the conceptual incoherencies (in section III) and moral problems (in section IV) that come with such an approach. Put shortly, the case of PGD shows that the luck egalitarian approach fails to express equal respect for the individual choices of people. The paradox of the matter is that by overemphasizing the fact of choice as such, without regard for the social framework in which they are being made, or for the fundamental and existential nature of particular choices-like choosing to have children and not to undergo PGD or not to abort a handicapped fetus-such choices actually become impossible. PMID:20181644

Denier, Yvonne



Application of genetic algorithms to fault diagnosis in nuclear power plants  

Microsoft Academic Search

A nuclear power plant (NPP) is a complex and highly reliable special system. Without expert knowledge, fault confirmation in the NPP can be prevented by illusive and real-time signals. A new method of fault diagnosis, based on genetic algorithms (GAs) has been developed to resolve this problem. This NPP fault diagnosis method combines GAs and classical probability with an expert

Zhou Yangping; Zhao Bingquan; Wu DongXin



A Hybrid Computational Intelligence Approach Combining Genetic Programming and Heuristic Classification for Pap-Smear Diagnosis  

E-print Network

Classification for Pap-Smear Diagnosis Athanasios Tsakonas, Georgios Dounias, Jan Jantzen* and Beth Bjerregaard computational intelligence, medical diagnosis, pap-smear test, genetic programming, heuristic classification-known Pap-Test problem, corresponding to a numerical database, which consists of 450 medical records, 25

Fernandez, Thomas


A genetic algorithm for pancreatic cancer diagnosis Charalampos Moschopoulos1,2  

E-print Network

A genetic algorithm for pancreatic cancer diagnosis Charalampos Moschopoulos1,2 , Dusan Popovic1 to constitute a high reliability pancreatic cancer predictor. Keywords: genetic algorithm, support vector.DeMoor, Yves.Moreau}, Abstract. Pancreatic cancer is one of the leading causes


The interface between assisted reproductive technologies and genetics: technical, social, ethical and legal issues.  


The interface between assisted reproductive technologies (ART) and genetics comprises several sensitive and important issues that affect infertile couples, families with severe genetic diseases, potential children, professionals in ART and genetics, health care, researchers and the society in general. Genetic causes have a considerable involvement in infertility. Genetic conditions may also be transmitted to the offspring and hence create transgenerational infertility or other serious health problems. Several studies also suggest a slightly elevated risk of birth defects in children born following ART. Preimplantation genetic diagnosis (PGD) has become widely practiced throughout the world for various medical indications, but its limits are being debated. The attitudes towards ART and PGD vary substantially within Europe. The purpose of the present paper was to outline a framework for development of guidelines to be issued jointly by European Society of Human Genetics and European Society of Human Reproduction and Embryology for the interface between genetics and ART. Technical, social, ethical and legal issues of ART and genetics will be reviewed. PMID:16636693

Soini, Sirpa; Ibarreta, Dolores; Anastasiadou, Violetta; Aymé, Ségolène; Braga, Suzanne; Cornel, Martina; Coviello, Domenico A; Evers-Kiebooms, Gerry; Geraedts, Joep; Gianaroli, Luca; Harper, Joyce; Kosztolanyi, György; Lundin, Kersti; Rodrigues-Cerezo, Emilio; Sermon, Karen; Sequeiros, Jorge; Tranebjaerg, Lisbeth; Kääriäinen, Helena



Guidelines for the genetic diagnosis of hereditary recurrent fevers  

PubMed Central

Hereditary recurrent fevers (HRFs) are a group of monogenic autoinflammatory diseases characterised by recurrent bouts of fever and serosal inflammation that are caused by pathogenic variants in genes important for the regulation of innate immunity. Discovery of the molecular defects responsible for these diseases has initiated genetic diagnostics in many countries around the world, including the Middle East, Europe, USA, Japan and Australia. However, diverse testing methods and reporting practices are employed and there is a clear need for consensus guidelines for HRF genetic testing. Draft guidelines were prepared based on current practice deduced from previous HRF external quality assurance schemes and data from the literature. The draft document was disseminated through the European Molecular Genetics Quality Network for broader consultation and amendment. A workshop was held in Bruges (Belgium) on 18 and 19 September 2011 to ratify the draft and obtain a final consensus document. An agreed set of best practice guidelines was proposed for genetic diagnostic testing of HRFs, for reporting the genetic results and for defining their clinical significance. PMID:22661645

Shinar, Y; Obici, L; Aksentijevich, I; Bennetts, B; Austrup, F; Ceccherini, I; Costa, J M; De Leener, A; Gattorno, M; Kania, U; Kone-Paut, I; Lezer, S; Livneh, A; Moix, I; Nishikomori, R; Ozen, S; Phylactou, L; Risom, L; Rowczenio, D; Sarkisian, T; van Gijn, M E; Witsch-Baumgartner, M; Morris, M; Hoffman, H M; Touitou, I



Combined genetic and high-throughput strategies for molecular diagnosis of inherited retinal dystrophies.  


Most diagnostic laboratories are confronted with the increasing demand for molecular diagnosis from patients and families and the ever-increasing genetic heterogeneity of visual disorders. Concerning Retinal Dystrophies (RD), almost 200 causative genes have been reported to date, and most families carry private mutations. We aimed to approach RD genetic diagnosis using all the available genetic information to prioritize candidates for mutational screening, and then restrict the number of cases to be analyzed by massive sequencing. We constructed and optimized a comprehensive cosegregation RD-chip based on SNP genotyping and haplotype analysis. The RD-chip allows to genotype 768 selected SNPs (closely linked to 100 RD causative genes) in a single cost-, time-effective step. Full diagnosis was attained in 17/36 Spanish pedigrees, yielding 12 new and 12 previously reported mutations in 9 RD genes. The most frequently mutated genes were USH2A and CRB1. Notably, RD3-up to now only associated to Leber Congenital Amaurosis- was identified as causative of Retinitis Pigmentosa. The main assets of the RD-chip are: i) the robustness of the genetic information that underscores the most probable candidates, ii) the invaluable clues in cases of shared haplotypes, which are indicative of a common founder effect, and iii) the detection of extended haplotypes over closely mapping genes, which substantiates cosegregation, although the assumptions in which the genetic analysis is based could exceptionally lead astray. The combination of the genetic approach with whole exome sequencing (WES) greatly increases the diagnosis efficiency, and revealed novel mutations in USH2A and GUCY2D. Overall, the RD-chip diagnosis efficiency ranges from 16% in dominant, to 80% in consanguineous recessive pedigrees, with an average of 47%, well within the upper range of massive sequencing approaches, highlighting the validity of this time- and cost-effective approach whilst high-throughput methodologies become amenable for routine diagnosis in medium sized labs. PMID:24516651

de Castro-Miró, Marta; Pomares, Esther; Lorés-Motta, Laura; Tonda, Raul; Dopazo, Joaquín; Marfany, Gemma; Gonzàlez-Duarte, Roser



Combined Genetic and High-Throughput Strategies for Molecular Diagnosis of Inherited Retinal Dystrophies  

PubMed Central

Most diagnostic laboratories are confronted with the increasing demand for molecular diagnosis from patients and families and the ever-increasing genetic heterogeneity of visual disorders. Concerning Retinal Dystrophies (RD), almost 200 causative genes have been reported to date, and most families carry private mutations. We aimed to approach RD genetic diagnosis using all the available genetic information to prioritize candidates for mutational screening, and then restrict the number of cases to be analyzed by massive sequencing. We constructed and optimized a comprehensive cosegregation RD-chip based on SNP genotyping and haplotype analysis. The RD-chip allows to genotype 768 selected SNPs (closely linked to 100 RD causative genes) in a single cost-, time-effective step. Full diagnosis was attained in 17/36 Spanish pedigrees, yielding 12 new and 12 previously reported mutations in 9 RD genes. The most frequently mutated genes were USH2A and CRB1. Notably, RD3–up to now only associated to Leber Congenital Amaurosis– was identified as causative of Retinitis Pigmentosa. The main assets of the RD-chip are: i) the robustness of the genetic information that underscores the most probable candidates, ii) the invaluable clues in cases of shared haplotypes, which are indicative of a common founder effect, and iii) the detection of extended haplotypes over closely mapping genes, which substantiates cosegregation, although the assumptions in which the genetic analysis is based could exceptionally lead astray. The combination of the genetic approach with whole exome sequencing (WES) greatly increases the diagnosis efficiency, and revealed novel mutations in USH2A and GUCY2D. Overall, the RD-chip diagnosis efficiency ranges from 16% in dominant, to 80% in consanguineous recessive pedigrees, with an average of 47%, well within the upper range of massive sequencing approaches, highlighting the validity of this time- and cost-effective approach whilst high-throughput methodologies become amenable for routine diagnosis in medium sized labs. PMID:24516651

de Castro-Miro, Marta; Pomares, Esther; Lores-Motta, Laura; Tonda, Raul; Dopazo, Joaquin; Marfany, Gemma; Gonzalez-Duarte, Roser



Pharmacology and genetics of autism: implications for diagnosis and treatment  

PubMed Central

Autism has the highest estimated heritability (>90%) among behaviorally defined neuropsychiatric disorders. Rapidly advancing genomic technologies and large international collaborations have increased our understanding of the molecular genetic causes of autism. Pharmacogenomic approaches are currently being applied in two single-gene disorders, fragile X syndrome and Rett syndrome, which capture many aspects of the autistic phenotype. This review describes the current state of the genetics of autism and suggests how to extend pharmacological principles pioneered in fragile X and Rett to the broader group of patients with autism. PMID:19727434

Brkanac, Zoran; Raskind, Wendy H; King, Bryan H



Evolutionary genetics and molecular diagnosis of Leishmania species  

Microsoft Academic Search

An extensive study has been performed on various natural populations of Leishmania from the ‘Old’ and ‘New Worlds’ using multilocus enzyme electrophoresis and random amplification of polymorphic deoxyribonucleic acid. The data are interpreted in evolutionary genetic terms in order to give a firm basis to studies dealing with the relevant medical properties of pathogens. We confirm that Leishmania undergoes clonal

Anne-Laure Bañuls; Mallorie Hide; Michel Tibayrenc



Genetic studies on house rot fungi and a rapid diagnosis  

Microsoft Academic Search

The paper describes genetic studies on house rot fungi and a rapid identification technique for them, viz. the true dry rot\\u000a fungus Serpula lacrymans, the wild merulius S. himantioides, the cellar fungus Coniophora puteana and the pore house fungi Antrodia vaillantii and Tyromyces placenta. The method ARDRA-ITS uses the internal transcribed spacer (ITS) of the ribosomal DNA (rDNA) which is

O. Schmidt; U. Moreth



Myeloproliferative neoplasms: contemporary diagnosis using histology and genetics  

Microsoft Academic Search

The 2008 WHO classification system for hematological malignancies is comprehensive and includes histology and genetic information. Myeloid neoplasms are now classified into five categories: acute myeloid leukemia, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS\\/MPN, and myeloid and\\/or lymphoid malignancies associated with eosinophilia and PDGFR or FGFR1 rearrangements. MPN are subclassified into eight separate entities: chronic myelogenous leukemia, polycythemia vera, essential

Radek Skoda; James W. Vardiman; Ayalew Tefferi



Decision Tree Support Vector Machine based on Genetic Algorithm for fault diagnosis  

Microsoft Academic Search

Decision tree support vector machine (DTSVM), which combines SVM and decision tree using the concept of dichotomy, is proposed to solve the multi-class fault diagnosis tasks. Since the classification performance of DTSVM is closely related to its structure, genetic algorithm is introduced into the formation of decision tree, to cluster the multi-classes with maximum distance between the clustering centers of

Qiang Wang; Huanhuan Chen; Yi Shen



Genetic programming as a method to develop powerful predictive models for clinical diagnosis  

E-print Network

, prevention of errors and the advice of clinical tests. Predicting duration or the possibility is well-known in the medical field. Categories and Subject Descriptors J.3 [Life and Medical Sciences]: Medical Information Systems General Terms Algorithms, Performance Keywords Genetic Programming, Diagnosis

Fernandez, Thomas


Feature Selection & Hybrid Decision Tree/Genetic Algorithm for Cancer Diagnosis based on Mass Spectrometry Proteomics  

E-print Network

Feature Selection & Hybrid Decision Tree/Genetic Algorithm for Cancer Diagnosis based on Mass was caused by cancer (US centre for statistics on cancer), whilst ovarian cancer accounts for 4% of all female cancers, 90% of those women could be saved if the disease was detected at stage I [1]. Mass

Yao, Xin


First-trimester genetic diagnosis: a series of six cases.  


A first-trimester screen consists of a nuchal translucency (NT) ultrasound measurement as well as maternal serum testing for pregnancy-associated plasma protein-A (PAPP-A) and human chorionic gonadotropin (hCG). An increased nuchal translucency (NT) thickness at 11 to 14 weeks gestational age is a common finding for Down syndrome, Trisomy 18 and cardiac defects. We present a series of six patients, four with NT measurements greater than the 95th centile, and two additional cases where the NT was normal, but maternal serum biochemical markers were unusual. All six of these cases had a chromosome anomaly or another genetic condition: Noonan syndrome, triploidy, Down syndrome, Trisomy 18, Turner syndrome and a rare chromosome abnormality known as Ring 18-Monosomy 18. Our series underlines the fact that it is important to explore other genetic and chromosome abnormalities, in addition to Down syndrome and Trisomy 18, when there is an abnormality on a first-trimester screen. PMID:20301870

Stein, Quinn P; Flanagan, Jason D; Knutsen-Larson, Siri; Van Eerden, Peter



Small Ruminant Lentiviruses: Genetic Variability, Tropism and Diagnosis  

PubMed Central

Small ruminant lentiviruses (SRLV) cause a multisystemic chronic disease affecting animal production and welfare. SRLV infections are spread across the world with the exception of Iceland. Success in controlling SRLV spread depends largely on the use of appropriate diagnostic tools, but the existence of a high genetic/antigenic variability among these viruses, the fluctuant levels of antibody against them and the low viral loads found in infected individuals hamper the diagnostic efficacy. SRLV have a marked in vivo tropism towards the monocyte/macrophage lineage and attempts have been made to identify the genome regions involved in tropism, with two main candidates, the LTR and env gene, since LTR contains primer binding sites for viral replication and the env-encoded protein (SU ENV), which mediates the binding of the virus to the host’s cell and has hypervariable regions to escape the humoral immune response. Once inside the host cell, innate immunity may interfere with SRLV replication, but the virus develops counteraction mechanisms to escape, multiply and survive, creating a quasi-species and undergoing compartmentalization events. So far, the mechanisms of organ tropism involved in the development of different disease forms (neurological, arthritic, pulmonary and mammary) are unknown, but different alternatives are proposed. This is an overview of the current state of knowledge on SRLV genetic variability and its implications in tropism as well as in the development of alternative diagnostic assays. PMID:23611847

Ramírez, Hugo; Reina, Ramsés; Amorena, Beatriz; de Andrés, Damián; Martínez, Humberto A.



Narrative Review: Harnessing Molecular Genetics for the Diagnosis and Management of Hypertrophic Cardiomyopathy  

NSDL National Science Digital Library

Unexplained cardiac hypertrophy, the diagnostic criterion for hypertrophic cardiomyopathy (HCM), occurs in 1 in 500 adults. Insights into the genetic cause and molecular pathophysiology of HCM are reshaping clinical paradigms for diagnosis and treatment of this common myocardial disorder. Human genetic studies have established that dominant mutations in the proteins that make up the contractile apparatus (the sarcomere) cause HCM. With the current availability of clinical gene-based diagnostics, pathogenic mutations in affected patients can be defined, which can suggest a clinical course and allow definitive preclinical identification of family members at risk for HCM. Genetic discoveries have also fostered mechanistic investigations in model organisms that are engineered to carry human HCM mutations. Novel therapeutic targets have emerged from these fundamental studies and are currently under clinical assessment in humans. The combination of contemporary gene-based diagnosis with new strategies to attenuate disease development and progression is changing the natural history of lifelong cardiac symptoms, arrhythmias, and heart failure from HCM.

Libin Wang (University of Miami); Jonathan G. Seidman (Harvard Medical School); Christine E. Seidman (Harvard Medical School)



Gestational trophoblastic diseases: recent advances in histopathologic diagnosis and related genetic aspects.  


Gestational trophoblastic disease refers to a spectrum of proliferative disorders of the placental trophoblast, with a wide range of histologic appearances and clinical behaviors. This review discusses the more recent developments in the diagnosis of these entities. Changes in criteria for the histologic diagnosis of these lesions due to earlier clinical diagnosis are reviewed, and the ability to make more accurate diagnoses due to the introduction of newer antibodies such as p57 is highlighted. A discussion of epithelioid trophoblastic tumor, a newly introduced tumor subtype, with its differential diagnosis from placental-site trophoblastic tumor and squamous cell carcinoma is also presented. Last, a brief discussion on the role of genetic studies and the future direction of research in elucidating the nature of this intriguing group of lesions is presented. PMID:15900112

Hui, Pei; Martel, Maritza; Parkash, Vinita



Genetic diagnosis of autism spectrum disorders: The opportunity and challenge in the genomics era.  


Abstract A genetic etiology for autism spectrum disorders (ASDs) was first suggested from twin studies reported in the 1970s. The identification of gene mutations in syndromic ASDs provided evidence to support a genetic cause of ASDs. More recently, genome-wide copy number variant and sequence analyses have uncovered a list of rare and highly penetrant copy number variants (CNVs) or single nucleotide variants (SNVs) associated with ASDs, which has strengthened the claim of a genetic etiology for ASDs. Findings from research studies in the genetics of ASD now support an important role for molecular diagnostics in the clinical genetics evaluation of ASDs. Various molecular diagnostic assays including single gene tests, targeted multiple gene panels and copy number analysis should all be considered in the clinical genetics evaluation of ASDs. Whole exome sequencing could also be considered in selected clinical cases. However, the challenge that remains is to determine the causal role of genetic variants identified through molecular testing. Variable expressivity, pleiotropic effects and incomplete penetrance associated with CNVs and SNVs also present significant challenges for genetic counseling and prenatal diagnosis. PMID:24878448

Jiang, Yong-Hui; Wang, Yi; Xiu, Xu; Choy, Kwong Wai; Pursley, Amber Nolen; Cheung, Sau W



Role of molecular genetics in transforming diagnosis of diabetes mellitus.  


Most common diseases also run in families as rare, monogenic forms. Diabetes is no exception. Mutations in approximately 20 different genes are now known to cause monogenic diabetes, a disease group that can be subclassified into maturity-onset diabetes of the young, neonatal diabetes and mitochondrial diabetes. In some families, additional features, such as urogenital malformations, exocrine pancreatic dysfunction and neurological abnormalities, are present and may aid the diagnostic classification. The finding of a mutation in monogenic diabetes may have implications for the prediction of prognosis and choice of treatment. Mutations in the GCK gene cause a mild form of diabetes, which seldom needs insulin and has a low risk for complications. By contrast, HNF1A mutations lead to a diabetes form that in severity, treatment and complication risk resembles Type 1 diabetes, although these patients may experience a good effect of sulfonylurea treatment. The majority of neonatal diabetes cases are caused by mutations in the K(ATP) channel genes ABCC8 and KCNJ11, and sulfonylurea therapy is then usually superior to insulin. Diseases with a considerable genetic component may now be explored by genome-wide approaches using next-generation DNA sequencing technology. We expect that within a few years important breakthroughs will be made in mapping cases of diabetes with a suspected, but still unsolved monogenic basis. PMID:21463240

Molven, Anders; Njølstad, Pål R



Genetic counseling, activism and 'genotype-first' diagnosis of developmental disorders.  


This paper presents a sociological examination of the role of genetic counselors as advocates, not only for patients and their families, but also for genetic conditions themselves. In becoming activists for new disorders, genetic counselors are helping to create new categories that will shape expectations and treatment regimens for both existing patients and those who are yet to be diagnosed. By virtue of their expertise and their position at the intersection of several key professions and constituencies, genetic counselors are likely to play a central role in the way the genetic testing technologies, and especially 'genotype-first' diagnosis, impacts the way we understand and categorize developmental difference. I outline some of the promises and dangers that this kind of activism holds for people with developmental disabilities, and particularly the challenge presented by systemic ascertainment bias in the face of genotype-phenotype uncertainty. I argue that new testing techniques like microarray analysis that do not need to be targeted on the basis of clinical presentation throw these challenges into sharp relief, and that the genetic counseling community should consider how to marry advocacy for new genetic conditions with an emphasis on the indeterminate developmental potential of every child. PMID:22820968

Navon, Daniel



Online Diagnosis System: A webserver for analysis of Sanger sequencing-based genetic testing data.  


Sanger sequencing is a well-established molecular technique for diagnosis of genetic diseases. In these tests, DNA sequencers produce vast amounts of data that need to be examined and annotated within a short period of time. To achieve this goal, an online bioinformatics platform that can automate the process is essential. However, to date, there is no such integrated bioinformatics platform available. To fulfill this gap, we developed the Online Diagnosis System (ODS), which is a freely available webserver and supports the commonly used file format of Sanger sequencing data. ODS seamlessly integrates base calling, single nucleotide variation (SNV) identification, and SNV annotation into one single platform. It also allows laboratorians to manually inspect the quality of the identified SNVs in the final report. ODS can significantly reduce the data analysis time therefore allows Sanger sequencing-based genetic testing to be finished in a timely manner. ODS is freely available at PMID:25063568

Sun, Kun; Yuen, Yuet-Ping; Wang, Huating; Sun, Hao



Genetic Heterogeneity of Beta Globin Mutations among Asian-Indians and Importance in Genetic Counselling and Diagnosis  

PubMed Central

There are an estimated 45 million carriers of ?-thalassemia trait and about 12,000–15,000 infants with ?-thalassemia major are born every year in India. Thalassemia major constitutes a significant burden on the health care system. The burden of thalassemia major can be decreased by premarital screening and prenatal diagnosis. The success of prenatal diagnosis requires proper knowledge of spectrum of ?-thalassemia mutations. In present study, ?-thalassemia mutations were characterized in 300 thalassemia cases from 2007 to 2010 using ARMS-PCR and DNA sequencing. The five most common mutations accounted 78.9% of the studied chromosomes that includes IVS1-5(G>C), Cod 41-42(-TCTT), Cod8-9(+G), Cod16(?C) and 619bp del. Though IVS1-5(G>C) is most common mutation in all the communities, the percentage prevalence were calculated on sub caste basis and found that IVS1-5(G>C) percentage prevalence varied from 25 to 60 in Aroras & Khatris and Thakur respectively. Interestingly Cod41-42(?TCTT) mutation which is the second commonest among the mutations reported was totally absent in Kayasthas and Muslim community. These findings have implications for providing molecular diagnosis, genetic counseling and prenatal diagnosis to high risk couples of ?-thalassemia. PMID:23350016

Kumar, Ravindra; Singh, Kritanjali; Panigrahi, Inusha; Agarwal, Sarita



Pitfalls in the molecular genetic diagnosis of Leber hereditary optic neuropathy (LHON)  

SciTech Connect

Pathogenetic mutations in mtDNA are found in the majority of patients with Leber hereditary optic neuropathy (LHON), and molecular genetic techniques to detect them are important for diagnosis. A false-positive molecular genetic error has adverse consequences for the diagnosis of this maternally inherited disease. The authors found a number of mtDNA polymorphisms that occur adjacent to known LHON-associated mutations and that confound their molecular genetic detection. These transition mutations occur at mtDNA nt 11779 (SfaNI site loss, 11778 mutation), nt 3459 (BsaHI site loss, 3460 mutation), nt 15258 (AccI site loss, 15257 mutation), nt 14485 (mismatch primer Sau3AI site loss, 14484 mutation), and nt 13707 (BstNI site loss, 13708 mutation). Molecular genetic detection of the most common pathogenetic mtDNA mutations in LHON, using a single restriction enzyme, may be confounded by adjacent polymorphisms that occur with a false-positive rate of 2%-7%. 19 refs.

Johns, D.R. (Beth Israel Hospital, Boston, MA (United States)); Neufeld, M.J. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States))



[The use of genetic engineering in veterinary medicine with examples from epidemiology, diagnosis and drug production].  


The results of genetic engineering have reached practical veterinary medicine already. Nevertheless there is a great lack of knowledge among those veterinarians who usually do not work with these methods. Therefore we want to give an introduction into the advantages and dangers of this technology concerning veterinary medicine. Some important analytical methods are explained. Related viruses such as WEE and EEE or canine parvovirus, feline parvovirus and mink enteritis virus, or the related coronaviruses FIPV and TGEV serve as examples for the possibilities in molecular diagnosis and epidemic monitoring. The history of the gl- mutants of PRV, now prescribed as vaccine strains in the FRG, is an example of the development of genetic engineered vaccines. A new generation of vaccines based on recombinant vaccinia viruses is imminent. Thus we have to be aware of the high risks and responsibility of everybody who is involved in these new systems, especially the scientist who produces genetically altered organisms. PMID:2112273

Mayr, A; Hübert, P



Prenatal diagnosis in haemophilia A: experience of the genetic diagnostic laboratory.  


The paper describes the experience of the Genetic Diagnostic Laboratory in prenatal testing for haemophilia A, an X-linked recessive disease caused by mutations in the F8 gene. Knowledge of a familial mutation prior to pregnancy can benefit prenatal diagnosis and decrease wait time for molecular testing during pregnancy. This is a retrospective review of a series of pregnant women who pursued F8 gene testing from December 1997 through May 2012, highlighting three cases, which demonstrate the technical complexities of analysis and the implications of not knowing carrier status prior to pregnancy. Mutations of the F8 gene were detected in affected males, obligate female carriers and suspected female carriers by DNA sequencing, inverse-PCR, qRT-PCR, Southern blot and exonic dosage analysis. The same methods were used to analyse prenatal samples from obligate or suspected female carriers upon request. Maternal cell contamination studies were performed for all prenatal samples analysed. Ninety-nine women pursued F8 testing during pregnancy, either for carrier status alone or carrier status and prenatal diagnosis. Ninety-one women (91%) requested carrier testing because they did not know their F8 mutation carrier status prior to pregnancy. Eight women requested prenatal diagnosis only, and only 4 of these were aware of their mutation status. Thirty-seven individuals were found to be mutation carriers. Forty-two prenatal samples were received for prenatal diagnosis. In total 21 foetuses were identified as mutation carriers. Mutation detection was complex and increased the turnaround time in some cases. Only four of 99 women who submitted samples for F8 testing were aware of their F8 mutation status prior to pregnancy. Knowledge of F8 mutation status prior to pregnancy allows for efficient prenatal diagnosis, when desired. Thus, preconception genetic counselling is required to inform patients of the available options and the complex and time-consuming nature of F8 testing. PMID:25196590

Kessler, L; Adams, R; Mighion, L; Walther, S; Ganguly, A



Noninvasive prenatal testing/noninvasive prenatal diagnosis: the position of the National Society of Genetic Counselors.  


The 1997 discovery of free fetal DNA in maternal plasma launched clinical researchers' efforts to establish a reliable method for non-invasive prenatal testing for fetal genetic conditions. Various methods, including, but not limited to, massively parallel sequencing (MPS) and selective analysis of cell-free fetal DNA in maternal plasma, have recently been developed as highly sensitive and specific noninvasive screening tools for common fetal chromosome aneuploidies. Incorporating these new noninvasive technologies into clinical practice will impact the current prenatal screening paradigm for fetal aneuploidy, in which genetic counseling plays an integral role. The National Society of Genetic Counselors (NSGC) currently supports Noninvasive Prenatal Testing/Noninvasive Prenatal Diagnosis (NIPT/NIPD) as an option for patients whose pregnancies are considered to be at an increased risk for certain chromosome abnormalities. NSGC urges that NIPT/NIPD only be offered in the context of informed consent, education, and counseling by a qualified provider, such as a certified genetic counselor. Patients whose NIPT/NIPD results are abnormal, or who have other factors suggestive of a chromosome abnormality, should receive genetic counseling and be given the option of standard confirmatory diagnostic testing. PMID:23334531

Devers, Patricia L; Cronister, Amy; Ormond, Kelly E; Facio, Flavia; Brasington, Campbell K; Flodman, Pamela



Cost effective approach on feature selection using genetic algorithms and fuzzy logic for diabetes diagnosis  

E-print Network

A way to enhance the performance of a model that combines genetic algorithms and fuzzy logic for feature selection and classification is proposed. Early diagnosis of any disease with less cost is preferable. Diabetes is one such disease. Diabetes has become the fourth leading cause of death in developed countries and there is substantial evidence that it is reaching epidemic proportions in many developing and newly industrialized nations. In medical diagnosis, patterns consist of observable symptoms along with the results of diagnostic tests. These tests have various associated costs and risks. In the automated design of pattern classification, the proposed system solves the feature subset selection problem. It is a task of identifying and selecting a useful subset of pattern-representing features from a larger set of features. Using fuzzy rule-based classification system, the proposed system proves to improve the classification accuracy.

Ephzibah, E P



Tuberculosis disease diagnosis using artificial neural network trained with genetic algorithm.  


Tuberculosis is a common and often deadly infectious disease caused by mycobacterium; in humans it is mainly Mycobacterium tuberculosis (Wikipedia 2009). It is a great problem for most developing countries because of the low diagnosis and treatment opportunities. Tuberculosis has the highest mortality level among the diseases caused by a single type of microorganism. Thus, tuberculosis is a great health concern all over the world, and in Turkey as well. This article presents a study on tuberculosis diagnosis, carried out with the help of multilayer neural networks (MLNNs). For this purpose, an MLNN with two hidden layers and a genetic algorithm for training algorithm has been used. The tuberculosis dataset was taken from a state hospital's database, based on patient's epicrisis reports. PMID:20703557

Elveren, Erhan; Yumu?ak, Nejat



Application of massively parallel sequencing to genetic diagnosis in multiplex families with idiopathic sensorineural hearing impairment.  


Despite the clinical utility of genetic diagnosis to address idiopathic sensorineural hearing impairment (SNHI), the current strategy for screening mutations via Sanger sequencing suffers from the limitation that only a limited number of DNA fragments associated with common deafness mutations can be genotyped. Consequently, a definitive genetic diagnosis cannot be achieved in many families with discernible family history. To investigate the diagnostic utility of massively parallel sequencing (MPS), we applied the MPS technique to 12 multiplex families with idiopathic SNHI in which common deafness mutations had previously been ruled out. NimbleGen sequence capture array was designed to target all protein coding sequences (CDSs) and 100 bp of the flanking sequence of 80 common deafness genes. We performed MPS on the Illumina HiSeq2000, and applied BWA, SAMtools, Picard, GATK, Variant Tools, ANNOVAR, and IGV for bioinformatics analyses. Initial data filtering with allele frequencies (<5% in the 1000 Genomes Project and 5400 NHLBI exomes) and PolyPhen2/SIFT scores (>0.95) prioritized 5 indels (insertions/deletions) and 36 missense variants in the 12 multiplex families. After further validation by Sanger sequencing, segregation pattern, and evolutionary conservation of amino acid residues, we identified 4 variants in 4 different genes, which might lead to SNHI in 4 families compatible with autosomal dominant inheritance. These included GJB2 p.R75Q, MYO7A p.T381M, KCNQ4 p.S680F, and MYH9 p.E1256K. Among them, KCNQ4 p.S680F and MYH9 p.E1256K were novel. In conclusion, MPS allows genetic diagnosis in multiplex families with idiopathic SNHI by detecting mutations in relatively uncommon deafness genes. PMID:23451214

Wu, Chen-Chi; Lin, Yin-Hung; Lu, Ying-Chang; Chen, Pei-Jer; Yang, Wei-Shiung; Hsu, Chuan-Jen; Chen, Pei-Lung



Application of Massively Parallel Sequencing to Genetic Diagnosis in Multiplex Families with Idiopathic Sensorineural Hearing Impairment  

PubMed Central

Despite the clinical utility of genetic diagnosis to address idiopathic sensorineural hearing impairment (SNHI), the current strategy for screening mutations via Sanger sequencing suffers from the limitation that only a limited number of DNA fragments associated with common deafness mutations can be genotyped. Consequently, a definitive genetic diagnosis cannot be achieved in many families with discernible family history. To investigate the diagnostic utility of massively parallel sequencing (MPS), we applied the MPS technique to 12 multiplex families with idiopathic SNHI in which common deafness mutations had previously been ruled out. NimbleGen sequence capture array was designed to target all protein coding sequences (CDSs) and 100 bp of the flanking sequence of 80 common deafness genes. We performed MPS on the Illumina HiSeq2000, and applied BWA, SAMtools, Picard, GATK, Variant Tools, ANNOVAR, and IGV for bioinformatics analyses. Initial data filtering with allele frequencies (<5% in the 1000 Genomes Project and 5400 NHLBI exomes) and PolyPhen2/SIFT scores (>0.95) prioritized 5 indels (insertions/deletions) and 36 missense variants in the 12 multiplex families. After further validation by Sanger sequencing, segregation pattern, and evolutionary conservation of amino acid residues, we identified 4 variants in 4 different genes, which might lead to SNHI in 4 families compatible with autosomal dominant inheritance. These included GJB2 p.R75Q, MYO7A p.T381M, KCNQ4 p.S680F, and MYH9 p.E1256K. Among them, KCNQ4 p.S680F and MYH9 p.E1256K were novel. In conclusion, MPS allows genetic diagnosis in multiplex families with idiopathic SNHI by detecting mutations in relatively uncommon deafness genes. PMID:23451214

Wu, Chen-Chi; Lin, Yin-Hung; Lu, Ying-Chang; Chen, Pei-Jer; Yang, Wei-Shiung; Hsu, Chuan-Jen; Chen, Pei-Lung



Stable 9 beta- or 11 alpha-halogen-15-cyclohexyl-prostaglandins with high affinity to the PGD2-receptor.  


Various chemically stable prostaglandin analogues were studied for their affinity towards the PGD2-receptor in human platelet membranes in order to define the requirements for specific ligand binding to this receptor. On replacing the 11- or 9-hydroxyl groups of PGF2 alpha by an 11 alpha- or 9 beta-chloro- or fluoro atom, stable prostaglandin analogues were obtained, which showed high affinity towards the PGD2-receptor. The lower side chain consisted of a 15-cyclohexyl group or of the natural 15-n-pentyl group, other substitutents decreased the affinity substantially. The highest PGD2-mimetic activity with a relative affinity of 0.5 to the PGD2-receptor was found in 9-deoxy-9 beta-chloro-16,17,18,19,20-pentanor-15-cyclohexyl-PGF2 alpha (ZK 110 841, compound 16 in Table 1). ZK 110 841 is a chemically stable crystalline substance, which is orally active and which might thus turn out to be an interesting tool for the study of PGD2-receptor interactions. Some other prostaglandin as well as prostacyclin analogues with a 15-cyclohexyl or 15-n-pentyl group exhibited in addition to their known high affinity to the PGE2-receptor of human uterine membranes or the PGI2-receptor of human platelets also affinities to the PGD2-receptor. Generally, the receptor affinities correlate with the activities as stimulators of adenylate cyclase and inhibitors of thrombin induced elevation of cytoplasmic free calcium as well as their ability to inhibit ADP-induced platelet aggregation. The PGI2-character regarding the effector systems prevails in compounds with affinity to both the PGI2- and PGD2-receptor. Compounds which bind to the PGE2- and PGD2-receptor show a flat dose response curve regarding platelet activation suggesting a mixture of pro- and antiaggregatory properties within these molecules. PMID:2847246

Thierauch, K H; Stürzebecher, C S; Schillinger, E; Rehwinkel, H; Radüchel, B; Skuballa, W; Vorbrüggen, H



Decisional authority and moral responsibility of patients and clinicians in the context of preimplantation genetic diagnosis.  


Case reports reveal that clinicians applying preimplantation genetic diagnosis are increasingly confronted with requests by patients which they consider ethically problematic. These requests raise the question to what extent physicians share responsibility for the welfare of the future child. Two categories of situations are analysed: when patients unilaterally review the agreement made with the medical staff and when they request an application that increases rather than reduces the risk of having a termination of pregnancy. It is concluded that physicians have their own responsibility in the process, which allows them to introduce conditions before starting infertility treatment. PMID:14686350

Pennings, Guido; Bonduelle, Maryse; Liebaers, Ingeborg



Appearing in Proceedings of AMIA Summit on Translational Bioinformatics (AMIA-TBI), 2014. New Genetic Variants Improve Personalized Breast Cancer Diagnosis  

E-print Network

Genetic Variants Improve Personalized Breast Cancer Diagnosis Jie Liu, MS1 , David Page, PhD1 , Peggy studies (GWAS) have identified a number of new genetic variants associated with breast cancer. However, the degree to which these genetic variants improve breast cancer diagnosis in concert with mammography

Page Jr., C. David


Fish based preimplantation genetic diagnosis to prevent DiGeorge syndrome  

Microsoft Academic Search

Purpose  To report the performance of fluorescence in-situ hybridization in the setting of preimplantation genetic diagnosis in order\\u000a to diagnose embryos affected by DiGeorge syndrome.\\u000a \\u000a \\u000a \\u000a Design  Case report.\\u000a \\u000a \\u000a \\u000a Setting  Academic referral center.\\u000a \\u000a \\u000a \\u000a Patient  A 32 year-old female affected by DiGeorge syndrome.\\u000a \\u000a \\u000a \\u000a Intervention(s)  History and physical examination, karyotyping, amniocentesis, preimplantation genetic diagnosis, fluorescence in-situ hybridization.\\u000a \\u000a \\u000a \\u000a Main outcome measure(s)  Avoidance of pregnancy with embryo affected by DiGeorge syndrome.\\u000a \\u000a \\u000a \\u000a Result(s)  Termination

Shai Shefi; Gil Raviv; Shlomit Rienstein; Gad Barkai; Ayala Aviram-Goldring; Jacob Levron



Rolling element bearing fault diagnosis based on the combination of genetic algorithms and fast kurtogram  

NASA Astrophysics Data System (ADS)

The rolling element bearing is a key part in many mechanical facilities and the diagnosis of its faults is very important in the field of predictive maintenance. Till date, the resonant demodulation technique (envelope analysis) has been widely exploited in practice. However, much practical diagnostic equipment for carrying out the analysis gives little flexibility to change the analysis parameters for different working conditions, such as variation in rotating speed and different fault types. Because the signals from a flawed bearing have features of non-stationarity, wide frequency range and weak strength, it can be very difficult to choose the best analysis parameters for diagnosis. However, the kurtosis of the vibration signals of a bearing is different from normal to bad condition, and is robust in varying conditions. The fast kurtogram gives rough analysis parameters very efficiently, but filter centre frequency and bandwidth cannot be chosen entirely independently. Genetic algorithms have a strong ability for optimization, but are slow unless initial parameters are close to optimal. Therefore, the authors present a model and algorithm to design the parameters for optimal resonance demodulation using the combination of fast kurtogram for initial estimates, and a genetic algorithm for final optimization. The feasibility and the effectiveness of the proposed method are demonstrated by experiment and give better results than the classical method of arbitrarily choosing a resonance to demodulate. The method gives more flexibility in choosing optimal parameters than the fast kurtogram alone.

Zhang, Yongxiang; Randall, R. B.



Genetic diagnosis of idiopathic hypogonadotrophic hypogonadism: a new point mutation in the KAL2 gene.  


Kallmann Syndrome (KS) is a genetic disease of embryonic development which is characterized by the association of hypogonadotropic hypogonadism (HH) due to a deficit of the gonadotropin-releasing hormone (GnRH) and a hypo/anosmia (including a hypoplasia of the nasal sulcus and agenesis of the olfactory bulbs). Even though it is a genotypically and phenotypically heterogeneous clinical disease, there are some key genes related to KS (KAL1, FGFR1 (KAL2), GNRHR, KISSR1 (GPR54), GNRH1, NELF and PROK2). The aim of this study was to present a case report of a genetic diagnosis of KS linked to the presence of mutations in the FGFR1 (fibroblast growth factor receptor 1, also known as KAL2) gene. This diagnosis was made in a 44-year old female affected by a hypogonadism for which she had received intermittent treatment until she was 30 years old based on the patient's own decision. The molecular analysis of FGFR1 identified the mutation c. 246_247delAG (p.T82Xfs110) in heterozygosis on exon 3 of the KAL2 gene. This is the first report of this mutation related to idiopathic hypogonadotrophic hypogonadism (IHH). PMID:24776628

Entrala-Bernal, Carmen; Montes-Castillo, Cristina; Alvarez-Cubero, Maria Jesus; Gutiérrez-Alcántara, Carmen; Fernandez-Rosado, Francisco; Martinez-Esp?n, Esther; Sánchez-Malo, Carolina; Santiago-Fernández, Piedad



Impact of genetics on the diagnosis and clinical management of syndromic craniosynostoses  

PubMed Central

Purpose More than 60 different mutations have been identified to be causal in syndromic forms of craniosynostosis. The majority of these mutations occur in the fibroblast growth factor receptor 2 gene (FGFR2). The clinical management of syndromic craniosynostosis varies based on the particular causal mutation. Additionally, the diagnosis of a patient with syndromic craniosynostosis is based on the clinical presentation, signs, and symptoms. The understanding of the hallmark features of particular syndromic forms of craniosynostosis leads to efficient diagnosis, management, and long-term prognosis of patients with syndromic craniosynostoses. Methods A comprehensive literature review was done with respect to the major forms of syndromic craniosynostosis and additional less common FGFR-related forms of syndromic craniosynostosis. Additionally, information and data gathered from studies performed in our own investigative lab (lab of Dr. Muenke) were further analyzed and reviewed. A literature review was also performed with regard to the genetic workup and diagnosis of patients with craniosynostosis. Results Patients with Apert syndrome (craniosynostosis syndrome due to mutations in FGFR2) are most severely affected in terms of intellectual disability, developmental delay, central nervous system anomalies, and limb anomalies. All patients with FGFR-related syndromic craniosynostosis have some degree of hearing loss that requires thorough initial evaluations and subsequent follow-up. Conclusions Patients with syndromic craniosynostosis require management and treatment of issues involving multiple organ systems which span beyond craniosynostosis. Thus, effective care of these patients requires a multidisciplinary approach. PMID:22872262

Agochukwu, Nneamaka B.; Solomon, Benjamin D.; Muenke, Maximilian



Genetics of frontotemporal lobar degeneration: an up-date and diagnosis algorithm.  


The last decade marked a turning point in the knowledge of frontotemporal lobar degenerations (FTLD). Major discoveries were made with the identification of TDP-43 and FUS, two novel key players in FTLD. The growing number of FTLD genes has considerably changed our clinical practice. The high intrafamilial variability of phenotypes underlines the necessity of a careful interview concerning the family history, regarding FTLD diseases, but also other neurodegenerative and extra-neurological disorders. Knowledge of the different genetic forms of FTLD and their associated phenotypes become essential to propose appropriate genetic diagnosis to the patients, and deliver accurate genetic counseling to their families. We propose an algorithm based on four criteria to help to pinpoint the genetic cause of FTLD: Presence of ALS in the patient or family; age at onset of FTLD; progranulin plasma level; and other disorders present in the patient or family. Presence of ALS is strongly indicative of a C9ORF72 expansion; a very early age at onset (<50 years), parkinsonism and oculomotor dysfunction are indicative of MAPT mutations; whereas hallucinations, CBDS and PNFA are indicative of PGRN mutations. A C9ORF72 repeat expansion should be searched for therefore in patients with FTLD-ALS, followed by sequencing of exon 6 of TARDBP gene in negative cases. Since C9ORF72 expansions are as frequent as PGRN mutations in patients with pure FTLD, both should be investigated, except in early familial FTLD (<50) where MAPT mutations should be searched for first. VCP, SQSTM1 and hnRNPA2B1 gene-sequencing could be proposed in patients or families presenting 'multisystem proteinopathy'. The genes currently identified explain 50-60% of familial forms of FTLD. The identification of new FTLD genes involved remains a major challenge to gain further insight into the pathology and even better clarify the classification of FTLD in the future. PMID:24011980

Le Ber, I



Comparison between ultrasound and genetic testing for the early diagnosis of polycystic kidney disease in Persian and Exotic Shorthair cats  

Microsoft Academic Search

Autosomal-dominant polycystic kidney disease (AD-PKD) is common in Persians and Persians-related breeds. The aims of this study were to evaluate the sensitivity and specificity of early ultrasound examination and to compare ultrasound and genetic testing for early diagnosis. Sixty-three Persians and seven Exotic Shorthairs were considered. All underwent ultrasonographic and genetic testing (polymerase chain reaction\\/restriction fragment length polymorphism (PCR\\/RFLP) assay)

Mattia Bonazzi; Antonella Volta; Giacomo Gnudi; Maria C. Cozzi; Maria G. Strillacci; Michele Polli; Maria Longeri; Sabrina Manfredi; Giorgio Bertoni



Molecular diagnosis reveals genetic heterogeneity for the overlapping MKKS and BBS phenotypes.  


Hydrometrocolpos and polydactyly diagnosed in the prenatal period or early childhood may raise diagnostic dilemmas especially in distinguishing McKusick-Kaufman syndrome (MKKS) and the Bardet-Biedl syndrome (BBS). These two conditions can initially overlap. With time, the additional features of BBS appearing in childhood, such as retinitis pigmentosa, obesity, learning disabilities and progressive renal dysfunction allow clear differentiation between BBS and MKKS. Genotype overlap also exists, as mutations in the MKKS-BBS6 gene are found in both syndromes. We report 7 patients diagnosed in the neonatal period with hydrometrocolpos and polydactyly who carry mutations in various BBS genes (BBS6, BBS2, BBS10, BBS8 and BBS12), stressing the importance of wide BBS genotyping in patients with this clinical association for diagnosis, prognosis and genetic counselling. PMID:21044901

Schaefer, Elise; Durand, Myriam; Stoetzel, Corinne; Doray, Bérénice; Viville, Brigitte; Hellé, Sophie; Danse, Jean-Marc; Hamel, Christian; Bitoun, Pierre; Goldenberg, Alice; Finck, Sonia; Faivre, Laurence; Sigaudy, Sabine; Holder, Muriel; Vincent, Marie-Claire; Marion, Vincent; Bonneau, Dominique; Verloes, Alain; Nisand, Israël; Mandel, Jean-Louis; Dollfus, Hélène



Prenatal Diagnosis of Congenital Lipoid Adrenal Hyperplasia (CLAH) by Molecular Genetic Testing in Korean Siblings  

PubMed Central

Congenital lipoid adrenal hyperplasia (CLAH) is caused by mutations to the steroidogenic acute regulatory protein (StAR) gene associated with the inability to synthesize all adrenal and gonadal steroids. Inadequate treatment in an infant with this condition may result in sudden death from an adrenal crisis. We report a case in which CLAH developed in Korean siblings; the second child was prenatally diagnosed because the first child was affected and low maternal serum estriol was detected in a prenatal screening test. To our knowledge, this is the first prenatal diagnosis of the Q258X StAR mutation, which is the only consistent genetic cluster identified to date in Japanese and Korean populations. PMID:22028173

Ko, Hyun Sun; Lee, Seungok; Chae, Hyojin; Choi, Sae Kyung; Kim, Myungshin; Park, In Yang; Suh, Byung Kyu



Association of Age at Diagnosis and Genetic Mutations in Patients with Neuroblastoma  

PubMed Central

Context Neuroblastoma is diagnosed over a wide age range from birth through young adulthood, and older age at diagnosis is associated with a decline in survivability. Objective To identify genetic mutations that are associated with age at diagnosis in patients with metastatic neuroblastoma. Design, Setting and Patients We performed whole genome sequencing of DNA from diagnostic tumors and their matched germlines from 40 patients with metastatic neuroblastoma obtained between 1987 and 2009. Age groups at diagnosis included infants (0-<18 months), children (18 months-<12 years), and adolescents and young adults (?12 years). To confirm the findings from this discovery cohort, validation testing using tumors from an additional 64 patients obtained between 1985 and 2009 was also performed. Formalin-fixed paraffin-embedded tumor tissue was used for immunohistochemistry and fluorescent in situ hybridization. Telomere lengths were analyzed using the whole genome sequencing data, quantitative polymerase chain reaction and fluorescent in situ hybridization. Main Outcome Measure Somatic recurrent mutations in tumors from patients with neuroblastoma correlated with the age at diagnosis and telomere length. Results We identified mutations in the ATRX gene in 100% (5/5) (95% CI, 50% – 100%) of tumors from patients in the adolescent and young adult group, 17% (5/29) (95% CI, 7% – 36%) of tumors from children, and 0% (0/6) (95% CI, 0% – 40%) of tumors from infants in the discovery cohort (n=40). In the validation cohort (n=64), we identified mutations in the ATRX gene in 33% (9/27) (95% CI, 17% – 54%) of tumors from patients in the adolescent and young adult group, 16% (4/25) (95% CI, 6% – 35%) of tumors from children, and 0% (0/12) (95% CI, 0% – 24%) of tumors from infants. We identified mutations in the ATRX gene in 44% (14/32) (95% CI, 28% – 62%) of tumors from patients in the adolescent and young adult group, 17% (9/54) (95% CI, 9% – 29%) of tumors from children, and 0% (0/18) (95% CI, 0% – 17%) of tumors from infants in the combined cohort (n=104). ATRX mutations were associated with an absence of ATRX protein in the nucleus and with long telomeres. Conclusions ATRX mutations were associated with age at diagnosis in children and young adults with stage 4 neuroblastoma. Clinical Protocol “Molecular Characterization of Neuroblastic Tumor: Correlation with Clinical Outcome” (clinical NCT00588068). PMID:22416102

Cheung, Nai-Kong V.; Zhang, Jinghui; Lu, Charles; Parker, Matthew; Bahrami, Armita; Tickoo, Satish K.; Heguy, Adriana; Pappo, Alberto S.; Federico, Sara; Dalton, James; Cheung, Irene Y.; Ding, Li; Fulton, Bob; Wang, Jianmin; Chen, Xiang; Becksfort, Jared; Wu, Jianrong; Billups, Catherine A.; Ellison, David; Mardis, Elaine R.; Wilson, Richard K.; Downing, James R.; Dyer, Michael A.



Genetics of hypertrophic cardiomyopathy: advances and pitfalls in molecular diagnosis and therapy  

PubMed Central

Hypertrophic cardiomyopathy (HCM) is a primary disease of the cardiac muscle that occurs mainly due to mutations (>1,400 variants) in genes encoding for the cardiac sarcomere. HCM, the most common familial form of cardiomyopathy, affecting one in every 500 people in the general population, is typically inherited in an autosomal dominant pattern, and presents variable expressivity and age-related penetrance. Due to the morphological and pathological heterogeneity of the disease, the appearance and progression of symptoms is not straightforward. Most HCM patients are asymptomatic, but up to 25% develop significant symptoms, including chest pain and sudden cardiac death. Sudden cardiac death is a dramatic event, since it occurs without warning and mainly in younger people, including trained athletes. Molecular diagnosis of HCM is of the outmost importance, since it may allow detection of subjects carrying mutations on HCM-associated genes before development of clinical symptoms of HCM. However, due to the genetic heterogeneity of HCM, molecular diagnosis is difficult. Currently, there are mainly four techniques used for molecular diagnosis of HCM, including Sanger sequencing, high resolution melting, mutation detection using DNA arrays, and next-generation sequencing techniques. Application of these methods has proven successful for identification of mutations on HCM-related genes. This review summarizes the features of these technologies, highlighting their strengths and weaknesses. Furthermore, current therapeutics for HCM patients are correlated with clinically observed phenotypes and are based on the alleviation of symptoms. This is mainly due to insufficient knowledge on the mechanisms involved in the onset of HCM. Tissue engineering alongside regenerative medicine coupled with nanotherapeutics may allow fulfillment of those gaps, together with screening of novel therapeutic drugs and target delivery systems. PMID:25328416

Roma-Rodrigues, Catarina; Fernandes, Alexandra R



Attitudes towards Genetic Diagnosis in Pakistan: A Survey of Medical and Legal Communities and Parents of Thalassemic Children  

Microsoft Academic Search

Objectives: It was the aim of this study to assess the attitudes of doctors, medical students, lawyers, parliament members and parents of thalassemic children towards genetic diagnosis in Pakistan. Study Design: A cross-sectional descriptive survey was conducted among representative samples. Results: Five hundred and seventy doctors, 49 lawyers, 178 medical students, 89 parents of thalassemic children and 16 members of

Ahmed I. Gilani; Atif S. Jadoon; Rabia Qaiser; Sana Nasim; Riffat Meraj; Nosheen Nasir; Fizza F. Naqvi; Zafar Latif; Muhammad A. Memon; Esme V. Menezes; Imran Malik; Muhammad Z. Memon; Syed F. Kazim; Usman Ahmad



Use of the MLPA Assay in the Molecular Diagnosis of Gene Copy Number Alterations in Human Genetic Diseases  

PubMed Central

Multiplex Ligation-dependent Probe Amplification (MLPA) assay is a recently developed technique able to evidence variations in the copy number of several human genes. Due to this ability, MLPA can be used in the molecular diagnosis of several genetic diseases whose pathogenesis is related to the presence of deletions or duplications of specific genes. Moreover, MLPA assay can also be used in the molecular diagnosis of genetic diseases characterized by the presence of abnormal DNA methylation. Due to the large number of genes that can be analyzed by a single technique, MLPA assay represents the gold standard for molecular analysis of all pathologies derived from the presence of gene copy number variation. In this review, the main applications of the MLPA technique for the molecular diagnosis of human diseases are described. PMID:22489151

Stuppia, Liborio; Antonucci, Ivana; Palka, Giandomenico; Gatta, Valentina



Hematopoietic-Prostaglandin D2 synthase through PGD2 production is involved in the adult ovarian physiology  

Microsoft Academic Search

Background  The prostaglandin D2 (PGD2) pathway is involved in numerous biological processes and while it has been identified as a partner\\u000a of the embryonic sex determining male cascade, the roles it plays in ovarian function remain largely unknown. PGD2 is secreted\\u000a by two prostaglandin D synthases (Pgds); the male-specific lipocalin (L)-Pgds and the hematopoietic (H)-Pgds.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  To study the expression of the

Andalib Farhat; Pascal Philibert; Charles Sultan; Francis Poulat; Brigitte Boizet-Bonhoure



Comparison between ultrasound and genetic testing for the early diagnosis of polycystic kidney disease in Persian and Exotic Shorthair cats.  


Autosomal-dominant polycystic kidney disease (AD-PKD) is common in Persians and Persians-related breeds. The aims of this study were to evaluate the sensitivity and specificity of early ultrasound examination and to compare ultrasound and genetic testing for early diagnosis. Sixty-three Persians and seven Exotic Shorthairs were considered. All underwent ultrasonographic and genetic testing (polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) assay) between 2.5 and 3.5 months of age (10-14 weeks). With ultrasound, 41.4% showed renal cysts, while 37.1% were PKD positive by genetic testing and DNA sequencing. Six cats with at least one renal cyst were negative by genetic testing, while only one cat negative at ultrasound resulted positive at genetic test. DNA sequencing of three polycystic cats, negative by genetic test, revealed they were heterozygous for the mutation. Agreement was described by Cohen's kappa that resulted 0.85, considering genetic test and DNA sequencing. Sensitivity and specificity of ultrasound were 96.2% and 91%, respectively. Sensitivity was higher and specificity lower than reported previously. The higher sensitivity could be due to improved technical capabilities of ultrasound machines and transducers. Other causes of PKD could explain the lower specificity. In conclusion, ultrasound resulted in a reliable diagnostic method for feline AD-PKD1 at early age and it should always be used with genetic testing, in order to reach a complete screening programme and eventually to identify other genetic mutations. PMID:19046910

Bonazzi, Mattia; Volta, Antonella; Gnudi, Giacomo; Cozzi, Maria C; Strillacci, Maria G; Polli, Michele; Longeri, Maria; Manfredi, Sabrina; Bertoni, Giorgio



Prenatal diagnosis as a tool and support for eugenics: myth or reality in contemporary French society?  


Today, French public debate and bioethics research reflect an ongoing controversy about eugenics. The field of reproductive medicine is often targeted as pre-implantation genetic diagnosis (PGD), prenatal diagnosis, and prenatal detection are accused of drifting towards eugenics or being driven by eugenics considerations. This article aims at understanding why the charge against eugenics came at the forefront of the ethical debate. Above all, it aims at showing that the charge against prenatal diagnosis is groundless. The point of view presented in this article has been elaborated jointly by a geneticist and a philosopher. Besides a survey of the medical, bioethical, philosophical and social sciences literature on the topic, the methodology is founded on a joint analysis of geneticist's various consults. Evidence from office visits demonstrated that prenatal diagnosis leads to case-by-case decisions. As we have suggested, this conclusion does not mean that prenatal diagnosis is devoid of ethical issues, and we have identified at least two. The first is related to the evaluation of a decision to abort. The second line of ethical questions arises from the fact that the claim for "normality" hardly hides normative and ambiguous views about disability. As a conclusion, ethical dilemmas keep being noticeable in the field of reproductive medicine and genetic counselling, but an enquiry about eugenic tendencies probably does not allow us to understand them in the proper way. PMID:22814726

Gaille, Marie; Viot, Géraldine



Defined morphological criteria allow reliable diagnosis of colorectal serrated polyps and predict polyp genetics.  


Criteria for the diagnosis of serrated colorectal lesions (hyperplastic polyp, sessile serrated adenoma without or with dysplasia--which we called mixed polyp--and traditional serrated adenoma) for which consensus has been reached should be validated for applicability in daily practice in terms of inter-observer reproducibility and their association with clinical features and (epi)genetic events. A study set was created from a consecutive series of colorectal polyps (n?=?1,926) by selecting all sessile serrated adenomas, traditional serrated adenomas and mixed polyps. We added consecutive series of hyperplastic polyps, classical adenomas and normal mucosa samples for a total of 200 specimens. With this series, we conducted an inter-observer study, encompassing ten pathologists with gastrointestinal pathology experience from five European countries, in three rounds in which all cases were microscopically evaluated. An assessment of single morphological criteria was included, and these were correlated with clinical parameters and the mutation status of KRAS, BRAF and PIK3CA and the methylation status of MLH1. Gender, age and localisation were significantly associated with certain types of lesions. Kappa statistics revealed moderate to good inter-observer agreement for polyp classification (? = 0.56 to 0.63), but for single criteria, this varied considerably (? = 0.06 to 0.82). BRAF mutations were frequently found in hyperplastic polyps (86 %, 62/72) and sessile serrated adenomas (80 %, 41/51). KRAS mutations occurred more frequently in traditional serrated adenomas (78 %, 7/9) and less so in classical adenomas (20 %, 10/51). Single morphological criteria for sessile serrated adenomas showed significant correlation with BRAF mutation (all p???0.001), and those for classical adenomas or traditional serrated adenoma correlated significantly with KRAS mutation (all p?genetic alterations in colorectal polyps. PMID:24728704

Rau, Tilman T; Agaimy, Abbas; Gehoff, Anastasia; Geppert, Carol; Jung, Klaus; Knobloch, Katharina; Langner, Cord; Lugli, Alessandro; Groenbus-Lurkin, Irene; Nagtegaal, Iris D; Rüschoff, Josef; Saegert, Xavier; Sarbia, Mario; Schneider-Stock, Regine; Vieth, Michael; Zwarthoff, Ellen C; Hartmann, Arndt



Gender differences in career and practice patterns of PGD-trained dentists.  


This study compares differences by gender in the practice patterns and professional activities of general dentists, specialists, and dentists with Advanced Education in General Dentistry (AEGD) or General Practice Residency (GPR) training. The UCLA School of Dentistry surveyed a random sample of 6,725 dentists graduating from dental school in 1989, 1993, and 1997 as part of an evaluation of the impact of federal funding on postgraduate general dentist (PGD) programs. The survey asked about current practice, services referred and provided, and professional activities. Of the 2,029 dentists (30 percent) who responded, 49 percent were general dentists with no specialty training; 7 percent had AEGD training; 20 percent had GPR training; and 24 percent had specialty training. General dentists were more likely to be in private practice (p < 0.05). AEGDs, specialists, and females were more likely to report faculty positions as a secondary occupation. General dentists were more likely to be practice owners than AEGD- or GPR-trained dentists. The mean number of patients seen was highest for specialists. Females reported fewer patients than males, and this difference was significant for GPR-trained dentists. With respect to services, GPR-trained dentists reported significantly more biopsy procedures, conscious sedation, periodontal surgery, and implants than general dentists. AEGD-trained dentists reported more conscious sedation than general dentists. GPR dentists were more likely to volunteer time than general dentists without specialty training. PGD training appears to result in different types of employment and specific practice patterns that strengthen primary care dentistry. We further conclude that there are gender differences in the types of practice, patients seen, and services provided. These findings occur in addition to training differences. PMID:12521062

Atchison, Kathryn A; Bibb, Carol A; Lefever, Karen H; Mito, Ronald S; Lin, Sylvia; Engelhardt, Rita



Cancer genetics-guided discovery of serum biomarker signatures for diagnosis and prognosis of prostate cancer  

PubMed Central

A key barrier to the realization of personalized medicine for cancer is the identification of biomarkers. Here we describe a two-stage strategy for the discovery of serum biomarker signatures corresponding to specific cancer-causing mutations and its application to prostate cancer (PCa) in the context of the commonly occurring phosphatase and tensin homolog (PTEN) tumor-suppressor gene inactivation. In the first stage of our approach, we identified 775 N-linked glycoproteins from sera and prostate tissue of wild-type and Pten-null mice. Using label-free quantitative proteomics, we showed that Pten inactivation leads to measurable perturbations in the murine prostate and serum glycoproteome. Following bioinformatic prioritization, in a second stage we applied targeted proteomics to detect and quantify 39 human ortholog candidate biomarkers in the sera of PCa patients and control individuals. The resulting proteomic profiles were analyzed by machine learning to build predictive regression models for tissue PTEN status and diagnosis and grading of PCa. Our approach suggests a general path to rational cancer biomarker discovery and initial validation guided by cancer genetics and based on the integration of experimental mouse models, proteomics-based technologies, and computational modeling. PMID:21300890

Cima, Igor; Schiess, Ralph; Wild, Peter; Kaelin, Martin; Schuffler, Peter; Lange, Vinzenz; Picotti, Paola; Ossola, Reto; Templeton, Arnoud; Schubert, Olga; Fuchs, Thomas; Leippold, Thomas; Wyler, Stephen; Zehetner, Jens; Jochum, Wolfram; Buhmann, Joachim; Cerny, Thomas; Moch, Holger; Gillessen, Silke; Aebersold, Ruedi; Krek, Wilhelm



Optimizing the feature set for a Bayesian network for breast cancer diagnosis using genetic algorithm techniques  

NASA Astrophysics Data System (ADS)

This study investigates the degree to which the performance of Bayesian belief networks (BBNs), for computer-assisted diagnosis of breast cancer, can be improved by optimizing their input feature sets using a genetic algorithm (GA). 421 cases (all women) were used in this study, of which 92 were positive for breast cancer. Each case contained both non-image information and image information derived from mammograms by radiologists. A GA was used to select an optimal subset of features, from a total of 21, to use as the basis for a BBN classifier. The figure-of-merit used in the GA's evaluation of feature subsets was Az, the area under the ROC curve produced by the corresponding BBN classifier. For each feature subset evaluated by the GA, a BBN was developed to classify positive and negative cases. Overall performance of the BBNs was evaluated using a jackknife testing method to calculate Az, for their respective ROC curves. The Az value of the BBN incorporating all 21 features was 0.851 plus or minus 0.012. After a 93 generation search, the GA found an optimal feature set with four non-image and four mammographic features, which achieved an Az value of 0.927 plus or minus 0.009. This study suggests that GAs are a viable means to optimize feature sets, and optimizing feature sets can result in significant performance improvements.

Wang, Xiao Hui; Zheng, Bin; Chang, Yuan-Hsiang; Good, Walter F.



Combining fetal sonography with genetic and allele pathogenicity studies to secure a neonatal diagnosis of Bardet-Biedl syndrome.  


Bardet-Biedl syndrome (BBS) is a rare pediatric ciliopathy characterized by marked clinical variability and extensive genetic heterogeneity. Typical diagnosis of BBS is secured at a median of 9 years of age, and sometimes well into adolescence. Here, we report a patient in whom prenatal detection of increased nuchal fold, enlarged echogenic kidneys, and polydactyly prompted us to screen the most commonly mutated genes in BBS and the phenotypically and genetically overlapping ciliopathy, Meckel-Gruber syndrome (MKS). We identified the common Met390Arg mutation in BBS1 in compound heterozygosity with a novel intronic variant of unknown significance (VUS). Testing of mRNA harvested from primary foreskin fibroblasts obtained shortly after birth revealed the VUS to induce a cryptic splice site, which in turn led to a premature termination and mRNA degradation. To our knowledge, this is the earliest diagnosis of BBS in the absence of other affected individuals in the family, and exemplifies how combining clinical assessment with genetic and timely assays of variant pathogenicity can inform clinical diagnosis and assist with patient management in the prenatal and neonatal setting. PMID:22998390

Ashkinadze, E; Rosen, T; Brooks, S S; Katsanis, N; Davis, E E



KRT9 gene mutation as a reliable indicator in the prenatal molecular diagnosis of epidermolytic palmoplantar keratoderma.  


Epidermolytic palmoplantar keratoderma (EPPK) is the most frequent form of such keratodermas. It is inherited in an autosomal dominant pattern and is clinically characterized by diffuse yellowish thickening of the skin on the palms and soles with erythematous borders during the first weeks or months after birth. EPPK is generally caused by mutations of the KRT9 gene. More than 26 KRT9 gene mutations responsible for EPPK have been described (Human Intermediate Filament Database,, and many of these variants are located within the highly-conserved coil 1A region of the ?-helical rod domain of keratin 9. Unfortunately, there is no satisfactory treatment for EPPK. Thus, prenatal molecular diagnosis or pre-pregnancy diagnosis is crucial and benefits those affected who seek healthy descendants. In the present study, we performed amniotic fluid-DNA-based prenatal testing for three at-risk pregnant EPPK women from three unrelated southern Chinese families who carried the KRT9 missense mutations p.Arg163Trp and p.Arg163Gln, and successfully helped two families to bear normal daughters. We suggest that before the successful application of preimplantation genetic diagnosis (PGD), and noninvasive prenatal diagnosis of EPPK that analyzes fetal cells or cell-free DNA in maternal blood, prenatal genetic diagnosis by amniocentesis or chorionic villus sampling (CVS) offers a quite acceptable option for EPPK couples-at-risk to avoid the birth of affected offspring, especially in low- and middle-income countries. PMID:24862219

Ke, Hai-Ping; Jiang, Hu-Ling; Lv, Ya-Su; Huang, Yi-Zhou; Liu, Rong-Rong; Chen, Xiao-Ling; Du, Zhen-Fang; Luo, Yu-Qin; Xu, Chen-Ming; Fan, Qi-Hui; Zhang, Xian-Ning



The genetic basis and expanding role of molecular analysis in the diagnosis, prognosis, and therapeutic design for myelodysplastic syndromes.  


The myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders of ineffective hematopoiesis that characteristically demonstrate peripheral blood cytopenia, bone marrow hypercellularity, and morphologically defined dysplasia of one or more hematopoietic lineages. Classical metaphase cytogenetics and judicious use of fluorescence in situ hybridization play central roles in the contemporary diagnosis and classification of MDS. An abundance of recent molecular studies are beginning to delineate additional genetic and epigenetic aberrations associated with these disorders. These alterations affect diagnosis, prognosis, and therapy, and with this understanding classification systems are evolving from a primarily hematological and morphological basis toward a multifactorial appreciation that includes histomorphology, metaphase cytogenetics, and directed molecular studies. In the present health-care environment, it is critical to develop a cost-effective, efficient testing strategy that maximizes the diagnostic potential of even limited specimens. Here, we briefly review the classical genetic approach to MDS, outline exciting new advances in the molecular understanding of this heterogeneous group of hematological neoplasms, and discuss how these advances are driving the evolution of classification and prognostic systems. Rapidly growing understanding of the genetic basis of MDS holds much promise for testing, and here we provide a frame of reference for discussion of current testing protocols and for addressing testing modalities likely to enter clinical practice in the near future. PMID:24457119

Nybakken, Grant E; Bagg, Adam



Plasma 9?,11?-PGF2, a PGD2 metabolite, as a sensitive marker of mast cell activation by allergen in bronchial asthma  

Microsoft Academic Search

Background: Prostaglandin D2 (PGD2) is a major cyclooxygenase product generated by activated mast cells during an allergic response. Assessment of PGD2 and its metabolites in patients with asthma has mostly been performed in urine, bronchoalveolar lavage fluid and induced sputum, whereas human plasma determinations have been performed only sporadically.Methods: In 32 patients with allergic asthma and 50 healthy non-allergic controls,

G Bochenek; E Niz?ankowska; A Gielicz; M S?wierczyn?ska; A Szczeklik



Agonist and antagonist effects of 15R-prostaglandin (PG) D2 and 11-methylene-PGD2 on human eosinophils and basophils.  


Prostaglandin (PG) D2 acts through both the DP(1) receptor, which is coupled to adenylyl cyclase, and the DP2 receptor (chemoattractant receptor-homologous molecule expressed on Th2 cells), which is present on eosinophils, basophils, and Th2 cells and results in cell activation and migration. The most potent prostanoid DP2 agonist so far reported is 15R-methyl-PGD2, in which the hydroxyl group has the unnatural R configuration. In contrast, the corresponding analog possessing the natural 15S configuration is approximately 75 times less potent. This raised the question of whether the isoprostane 15R-PGD2 might have potent DP2 receptor-mediated biological activity. We therefore chemically synthesized 15R-PGD2 and investigated its biological activity. This compound elicited DP2 receptor-mediated CD11b expression in human basophils and eosinophils and induced actin polymerization and migration in eosinophils with a potency about the same as that of PGD2. In contrast, it had only a weak effect on DP1 receptor-mediated adenylyl cyclase activity in human platelets. We also investigated the effects of modification of the 9-hydroxyl and 11-oxo groups of PGD2. Both PGK2, in which the 9-hydroxyl group is replaced by an oxo group, and 11-deoxy-11-methylene PGD2, in which the 11-oxo group is replaced by a CH2 group, have little or no DP1 or DP2 agonist activity. However, the 11-methylene analog is a DP2 antagonist (IC50, approximately 2 microM). We conclude that 15R-PGD2, which may be generated by oxidative stress, is a potent and selective DP2 agonist and that modification of the 11-oxo group of PGD2 can result in DP2 antagonist activity. PMID:17041009

Cossette, Chantal; Walsh, Sinead E; Kim, Seongjin; Lee, Gue-Jae; Lawson, John A; Bellone, Sophie; Rokach, Joshua; Powell, William S



Pre-implantation diagnosis of aneuploidy by polar body and blastomere FISH analysis  

SciTech Connect

For preimplantation genetic diagnosis (PGD) of aneuploidy in human in-vitro fertilization (IVF), two blastomeres per embryo should be analyzed to minimize errors caused by FISH and mosaicism. But the biopsy of two cells from an 8-cell embryo can be detrimental. This can be substituted by initial FISH analysis of the first polar body (PB) and subsequent single blastomere analysis. Simultaneous FISH analysis of chromosomes X, Y, 18, 13/21 was used for first polar body aneuploidy analysis. Normal divalents appeared as single-dotted signals corresponding to their two chromatids. We found that pre-division of chromatids increased dramatically with time in culture. All but three pre-division events involved separation of chromatids within the PB or the egg, with a total of two chromatids in each. We concluded that PB aneuploidy analysis is safe when performed within 6 hours after egg retrieval. For our first clinical case we chose a 39 year-old female carrier of an X-linked disease already selected for FISH pre-implantation diagnosis. Eight polar bodies from 12 eggs were analyzed: six showed a normal X181321 complement of divalents; one had an extra chromatid for 13/21 (egg {number_sign}8); and one had a missing chromatid for 13/21 (egg {number_sign}10). After insemination, six fertilized eggs developed into embryos, including egg {number_sign}10 but not egg {number_sign}8. At day 3 of development, a single blastomere per embryo was analyzed by FISH. According to the blastomere analysis, one embryo was haploid, one tetraploid. The two normal female embryos were replaced and pregnancy and CFS results are pending. These results suggest that this technique can be successfully applied for PGD of major aneuploidies in IVF patients over 35. In addition, it indicates that studies on pre-division should be performed on eggs within six hours of retrieval.

Munne, S.; Cohen, J.; Grifo, J. [Cornell Univ., New York, NY (United States)] [and others



Selected AGXT gene mutations analysis provides a genetic diagnosis in 28% of Tunisian patients with primary hyperoxaluria  

PubMed Central

Background Primary hyperoxaluria type I (PH1) is a rare genetic disorder characterized by allelic and clinical heterogeneity. Four mutations (G170R, 33_34insC, I244T and F152I) account for more than 50% of PH1 alleles and form the basis for diagnostic genetic screening for PH1. We aimed to analyze the prevalence of these specific mutations causing PH1, and to provide an accurate tool for diagnosis of presymptomatic patients as well as for prenatal diagnosis in the affected families. Methods Polymerase chain reaction/Restriction Fragment Length Polymorphism, were used to detect the four mutations in the AGXT gene in DNA samples from 57 patients belonging to 40 families. Results Two mutations causing PH1 were detected in 24 patients (42.1%), with a predominance of the I244T mutation (68% of patients) and 33_34insC (in the remaining 32%). In 92% of cases, mutated alleles were in homozygous state. The presented clinical features were similar for the two mutations. The age of onset was heterogeneous with a higher frequency of the pediatric age. In 58.3% of cases, the presentation corresponded to advanced renal disease which occurred early (< 5 years) in the two mutations. In adolescents, only the I244T mutation was detected (41.1%). I244T and 33_34insC mutations were observed in adult patients, with 17.6% and 12.5% respectively. Conclusion Limited mutation analysis can provide a useful first line investigation for PH1. I244T and 33_34insC presented 28.2% of identified mutations causing disease in our cohort. This identification could provide an accurate tool for prenatal diagnosis in the affected families, for genetic counselling and for detection of presymptomatic individuals. PMID:21612638



Existing challenges associated with offering prenatal genetic diagnosis in an arab society in the sultanate of oman.  


The incidence of congenital anomalies and/or genetic disorders in the Omani population has reached figures greater than double the global statistics. Preference for consanguineous unions together with the fact that termination of pregnancy in Muslim communities are largely avoided, have been highlighted as contributing factors. This overview identifies a third significant aspect contributing to the elevated rate of genetic disorders in the Omani population. Namely, a lack of services that are able to offer termination of pregnancy for severe congenital anomalies, to requesting parents. In this report we select an unusual case of a family at risk for two distinct genetic disorders - 6q micro-deletion and unbalanced products of conception attributed to a balanced parental translocation involving chromosome 3 and 13, to portray and examine the current situation faced by Omani couples interested in prenatal diagnosis for termination of pregnancy. Additional challenges and pitfalls to developing a prenatal diagnostic service as part of the genetic service in Oman are discussed. PMID:25236482

Bruwer, Zandrè; Achandira, Udayakumar; Al Kharousi, Khalsa; Al-Kindy, Adila



Practice guidelines for the diagnosis and management of microcytic anemias due to genetic disorders of iron metabolism or heme synthesis.  


During recent years, our understanding of the pathogenesis of inherited microcytic anemias has gained from the identification of several genes and proteins involved in systemic and cellular iron metabolism and heme syntheses. Numerous case reports illustrate that the implementation of these novel molecular discoveries in clinical practice has increased our understanding of the presentation, diagnosis, and management of these diseases. Integration of these insights into daily clinical practice will reduce delays in establishing a proper diagnosis, invasive and/or costly diagnostic tests, and unnecessary or even detrimental treatments. To assist the clinician, we developed evidence-based multidisciplinary guidelines on the management of rare microcytic anemias due to genetic disorders of iron metabolism and heme synthesis. These genetic disorders may present at all ages, and therefore these guidelines are relevant for pediatricians as well as clinicians who treat adults. This article summarizes these clinical practice guidelines and includes background on pathogenesis, conclusions, and recommendations and a diagnostic flowchart to facilitate using these guidelines in the clinical setting. PMID:24665134

Donker, Albertine E; Raymakers, Reinier A P; Vlasveld, L Thom; van Barneveld, Teus; Terink, Rieneke; Dors, Natasja; Brons, Paul P T; Knoers, Nine V A M; Swinkels, Dorine W



Genetic testing: predictive value of genotyping for diagnosis and management of disease  

Microsoft Academic Search

This article describes predictive, preventive value of genetic tests and the implication of the use of testing for personalized\\u000a treatment. This year marks the 10th anniversity of publishing of the sequence of the human genome. One important area of application\\u000a of this mega project is a development of genetic tests for mutation detection in single gene disorders that has impact

Meral Özgüç



Diagnosis of Oral Cancer using Genetic Programming Technical Report CSTR-96-14  

E-print Network

' C' D' B F' D (sexual reproduction) Reproduction (asexual reproduction) B A C B A X Z Mutation Y or asexual reproduction, each individual taking on some of the characteristics of its parents. The most selected node of the parent crossover fragments are swapped between two parents Figure 1: Basic Genetic

Fernandez, Thomas


Prenatal Diagnosis of Thanatophoric Dysplasia by 3-D Helical Computed Tomography and Genetic Analysis  

Microsoft Academic Search

Objective: We report the first case of thanatophoric dysplasia (TD) successfully diagnosed in utero by a combination of 2-D ultrasound, computed tomography (CT) 3-D imaging and genetic analysis at 26 weeks’ gestation. Methods: Prenatal sonographic examinations performed at 23 weeks’ gestation revealed micromelic shortening of the limbs, reduced thoracic cavity and a presence of cloverleaf skull deformity. Based on these

Seiji Tsutsumi; Hideaki Sawai; Gen Nishimura; Kiyoshi Hayasaka; Hirohisa Kurachi



McKusik-Kaufman syndrome: prenatal diagnosis, genetics and follow up.  


McKusick-Kaufman syndrome (MKKS) is a rare autosomal recessive genetic disease with classical hexadactyly and hydrocolpos in females and sometimes cardiac abnormality. We report such a case diagnosed just before birth with a favourable outcome. From this case we describe and discuss all the prenatal sonographic signs which are not always present. On the genetic side, the gene has recently been localized together with the mutation responsible for MKKS. The phenotypic relationship between MKKS which has a good prognosis and Bardet-Biedl syndrome (BBS) with a worse prognosis requires great caution before diagnosing MKKS and a long follow-up is necessary to recognize obesity, growth retardation and pigmentary retinitis. PMID:12424774

Gaucherand, Pascal; Vavasseur-Monot, Chantal; Ollagnon, Elizabeth; Boisson, Catherine; Labaune, Jean-Marc; Basset, Thierry; Yared, George



Whole dystrophin gene analysis by next-generation sequencing: a comprehensive genetic diagnosis of Duchenne and Becker muscular dystrophy.  


Duchenne/Becker muscular dystrophies are the most frequent inherited neuromuscular diseases caused by mutations of the dystrophin gene. However, approximately 30 % of patients with the disease do not receive a molecular diagnosis because of the complex mutational spectrum and the large size of the gene. The introduction and use of next-generation sequencing have advanced clinical genetic research and might be a suitable method for the detection of various types of mutations in the dystrophin gene. To identify the mutational spectrum using a single platform, whole dystrophin gene sequencing was performed using next-generation sequencing. The entire dystrophin gene, including all exons, introns and promoter regions, was target enriched using a DMD whole gene enrichment kit. The enrichment libraries were sequenced on an Illumina HiSeq 2000 sequencer using paired read 100 bp sequencing. We studied 26 patients: 21 had known large deletion/duplications and 5 did not have detectable large deletion/duplications by multiplex ligation-dependent probe amplification technology (MLPA). We applied whole dystrophin gene analysis by next-generation sequencing to the five patients who did not have detectable large deletion/duplications and to five randomly chosen patients from the 21 who did have large deletion/duplications. The sequencing data covered almost 100 % of the exonic region of the dystrophin gene by ?10 reads with a mean read depth of 147. Five small mutations were identified in the first five patients, of which four variants were unreported in the database. The deleted or duplicated exons and the breakpoints in the five large deletion/duplication patients were precisely identified. Whole dystrophin gene sequencing by next-generation sequencing may be a useful tool for the genetic diagnosis of Duchenne and Becker muscular dystrophies. PMID:24770780

Wang, Yan; Yang, Yao; Liu, Jing; Chen, Xiao-Chun; Liu, Xin; Wang, Chun-Zhi; He, Xi-Yu



Pivotal roles of the parasite PGD2 synthase and of the host D prostanoid receptor 1 in schistosome immune evasion.  


Prostaglandins (PG) are important modulators of immune and inflammatory responses. We recently demonstrated that the production of PGD(2) by the helminthic parasite Schistosoma mansoni inhibits the migration of epidermal Langerhans cells (LC) to the draining lymph nodes (DLN). Here, we identify the responsible parasite enzyme as being a 28-kDa glutathione-S-transferase (termed Sm28GST). Intradermal injection of Sm28GST in wild-type (WT), but not in D prostanoid receptor (DP) 1-deficient mice abrogates the departure of LC from the epidermis after TNF-alpha or FITC treatment. During infection, DP1 deficiency restores LC migration, but does not enhance the rate of T cell proliferation in the skin DLN. However, relative to WT mice, DLN cells from DP1-deficient infected mice produce dramatically less IFN-gamma and IL-10, but equal amount of IL-4. Interestingly, infected DP1-deficient mice develop a more Th2-biased humoral immune response, a significantly reduced parasitemia and a decreased egg-induced inflammatory response in the liver and intestines. Taken together, we propose that DP1 activation by the Sm28GST-derived PGD(2) could represent a strategy for the schistosome to evade host immune defenses. We also suggest that DP1 is important in the Th1/Th2 balance of the immune response and in inflammatory reactions during infection. PMID:14515260

Hervé, Maxime; Angeli, Véronique; Pinzar, Elena; Wintjens, René; Faveeuw, Christelle; Narumiya, Shuh; Capron, André; Urade, Yoshihiro; Capron, Monique; Riveau, Gilles; Trottein, François



[Dilated cardiomyopathy (DCM) in dogs--pathological, clinical, diagnosis and genetic aspects].  


Dilated cardiomyopathy (DCM) is a heart disease which is often found in humans and animals. The age of onset of this progressive disease varies between 3 and 7 years of age. A juvenile form of DCM has been found in Portuguese Water Dogs and Doberman Pinscher Dogs. Some breeds such as Doberman pinscher, Newfoundland, Portuguese Water dog, Boxer, Great Dane, Cocker Spaniel and Irish Wolfhound exhibit a higher prevalence to DCM. There also seems to be a sex predisposition as male dogs are affected more often than female dogs and in Great Danes an X-linked recessive inheritance is likely. In Newfoundland and Boxer an autosomal dominant inheritance was found whereas an autosomal recessive inheritance was described in Portuguese Water Dogs. Atrial fibrillation as a cause or consequence of DCM is assumed for certain breeds. The causes of DCM are widely unknown in dogs. A genetic basis for this heart disease seems to exist. Apart from a few exceptions the mode of inheritance and the possible underlying gene mutations are not known for DCM in dogs. In humans mutations in several genes responsible for DCM have been identified. Comparative genetic analyses in dogs using genes causing DCM in men and a genome-wide scan with anonymus markers were not able to detect causative mutations or genomic regions harboring gene loci linked to DCM. The investigation of the genetic basis of canine DCM may lead to new insights into the pathogenesis of DCM and may result in new therapeutic approaches and breeding strategies. PMID:16320572

Broschk, C; Distl, O



Three prevalent mutations in a patient with phenylalanine hydroxylase deficiency: implications for diagnosis and genetic counselling.  

PubMed Central

Mutation analysis in a patient with mild hyperphenylalaninaemia showed three distinct base substitutions in exon 12 of the phenylalanine hydroxylase (PAH) gene. All three mutations, R413P, Y414C, and D415N, have previously been described as being independently associated with PAH deficiency. Family studies and independent analysis of the PAH alleles of the patient showed cosegregation of the R413P and Y414C mutations. Data on the ethnic background of the family provide evidence that the R413P mutation has occurred on a PAH allele carrying the Y414C mutation. Using current methods for mutation identification, the presence of two known mutations on a single PAH allele implies the risk of misdiagnosis of PAH deficiency and complicates genetic counselling. Our results stress the need for comprehensive mutation scanning of the PAH gene in diagnostic settings. Images PMID:8929956

Guldberg, P; Levy, H L; Henriksen, K F; Guttler, F



Exome sequencing improves genetic diagnosis of structural fetal abnormalities revealed by ultrasound.  


The genetic etiology of non-aneuploid fetal structural abnormalities is typically investigated by karyotyping and array-based detection of microscopically detectable rearrangements, and submicroscopic copy-number variants (CNVs), which collectively yield a pathogenic finding in up to 10% of cases. We propose that exome sequencing may substantially increase the identification of underlying etiologies. We performed exome sequencing on a cohort of 30 non-aneuploid fetuses and neonates (along with their parents) with diverse structural abnormalities first identified by prenatal ultrasound. We identified candidate pathogenic variants with a range of inheritance models, and evaluated these in the context of detailed phenotypic information. We identified 35 de novo single-nucleotide variants (SNVs), small indels, deletions or duplications, of which three (accounting for 10% of the cohort) are highly likely to be causative. These are de novo missense variants in FGFR3 and COL2A1, and a de novo 16.8 kb deletion that includes most of OFD1. In five further cases (17%) we identified de novo or inherited recessive or X-linked variants in plausible candidate genes, which require additional validation to determine pathogenicity. Our diagnostic yield of 10% is comparable to, and supplementary to, the diagnostic yield of existing microarray testing for large chromosomal rearrangements and targeted CNV detection. The de novo nature of these events could enable couples to be counseled as to their low recurrence risk. This study outlines the way for a substantial improvement in the diagnostic yield of prenatal genetic abnormalities through the application of next-generation sequencing. PMID:24476948

Carss, Keren J; Hillman, Sarah C; Parthiban, Vijaya; McMullan, Dominic J; Maher, Eamonn R; Kilby, Mark D; Hurles, Matthew E



Direct detection of common and rare inversion mutations in the genetic diagnosis of severe hemophilia A  

SciTech Connect

Approximately 50% of the cases of severe hemophilia A (factor VIII:C < 0.01 units/ml) may be due to gross rearrangements of the factor VIII gene. The mutation involves homologous sequences upstream of the factor VIII locus and within intron 22 in an intrachromosomal recombination, inversion, event. The rearrangements can readily be detected on a Southern blot using a probe that is complementary to sequences from within intron 22. We describe here the analysis of this mutation in 71 severe hemophilia A patients. Thirty two of the patients (45%) showed evidence of a rearrangement. Five different patterns of rearrangements were seen, two of which have previously been described and account for the majority of cases (pattern 1, 70% and pattern 2, 16%). Three other abnormal patterns were observed. The inversion mechanism does not usually result in the loss or gain of any genetic material, but in one patient, in whom a unique rearrangement pattern was observed (pattern 3), we have previously documented a gross deletion which removes exons 1-22 of the factor VII gene as well as sequences 5{prime} to the gene. In another individual a fourth pattern in which an extra 19.0 kb band is present was detected. In this case it is unclear as to whether the rearrangement is responsible for the disease or is simply coincident normal variation. A fifth pattern, in which an extra 16.0 kb band was detected, was observed in a family with a new mutation causing hemophilia A. The affected individual and his mother inherited a de novo rearrangement of the factor VIII gene from his unaffected grandfather, implicating it as the cause of the disease. In conclusion, testing for the factor VIII inversion mutation was positive in approximately 45% of severe hemophiliacs, 72% of whom were isolated cases, and as such should constitute the initial stage in the genetic testing protocol for these patients` families.

Windsor, A.S.; Lillicrap, D.P.; Taylor, S.A.M. [Queen`s Univ., Ontario (Canada)



Exome sequencing improves genetic diagnosis of structural fetal abnormalities revealed by ultrasound  

PubMed Central

The genetic etiology of non-aneuploid fetal structural abnormalities is typically investigated by karyotyping and array-based detection of microscopically detectable rearrangements, and submicroscopic copy-number variants (CNVs), which collectively yield a pathogenic finding in up to 10% of cases. We propose that exome sequencing may substantially increase the identification of underlying etiologies. We performed exome sequencing on a cohort of 30 non-aneuploid fetuses and neonates (along with their parents) with diverse structural abnormalities first identified by prenatal ultrasound. We identified candidate pathogenic variants with a range of inheritance models, and evaluated these in the context of detailed phenotypic information. We identified 35 de novo single-nucleotide variants (SNVs), small indels, deletions or duplications, of which three (accounting for 10% of the cohort) are highly likely to be causative. These are de novo missense variants in FGFR3 and COL2A1, and a de novo 16.8 kb deletion that includes most of OFD1. In five further cases (17%) we identified de novo or inherited recessive or X-linked variants in plausible candidate genes, which require additional validation to determine pathogenicity. Our diagnostic yield of 10% is comparable to, and supplementary to, the diagnostic yield of existing microarray testing for large chromosomal rearrangements and targeted CNV detection. The de novo nature of these events could enable couples to be counseled as to their low recurrence risk. This study outlines the way for a substantial improvement in the diagnostic yield of prenatal genetic abnormalities through the application of next-generation sequencing. PMID:24476948

Carss, Keren J.; Hillman, Sarah C.; Parthiban, Vijaya; McMullan, Dominic J.; Maher, Eamonn R.; Kilby, Mark D.; Hurles, Matthew E.



From clinical and biochemical to molecular genetic diagnosis of Wilson disease in Latvia.  


Wilson disease (WD) is an autosomal recessive disorder of copper metabolism characterized by hepatic and/or neurological damage. More than 300 mutations in the gene ATP7B causing this defect have been reported. The data on correlation between WD patient genotypes and clinical presentation are controversial. In this paper the results of ATP7B mutation analysis by testing for mutation H1069Q and direct sequencing of six exons together with the clinical data of 40 Latvian WD patients are presented. Two previously described and two novel mutations as well as one previously reported polymorphism were identified. The H1069Q mutation was present at 52.5% of the disease alleles. One individual among 157 healthy Latvians was also found to be a mutation H1069Q carrier. The estimated incidence of WD in Latvia is approximately 1 in 25600. Wide clinical variability was observed among individuals with the same ATP7B genotype, thus supporting the suggestion that modifying factors play an additional role in the pathogenesis of WD. An algorithm for the diagnosis of WD, including testing for mutation H1069Q, is recommended for the populations where mutation H1069Q accounts for 50% of WD alleles or more. PMID:19062534

Krumina, A; Keiss, J; Sondore, V; Chernushenko, A; Cernevska, G; Zarina, A; Micule, I; Piekuse, L; Kreile, M; Lace, B; Krumina, Z; Rozentale, B



Geoelectrical investigation of old/abandoned, covered landfill sites in urban areas: model development with a genetic diagnosis approach  

NASA Astrophysics Data System (ADS)

Geoelectrical methods have an important, albeit difficult role to play in landfill investigations. In the present economic conditions, with the environmentally sensitive regime, adequate desk-study and model development are essential ingredients for a successful site investigation of landfills. This paper attempts to develop a genetic investigative model for old/abandoned landfill sites where the records of operations are not available. The main elements of the model are the site boundaries, age and nature of anthropogenic deposits, depth and dip of the layers of refuse and sealing materials, the integrity and shape of the capping zones or separating walls and basal floor slopes, the position of concealed access roads in the site, the water table (or perched water bodies within the refuse) and the presence of leachate. The attendant geotechnical, hydrogeological, and bio-geochemical constraints at such sites are also incorporated in the model for consistency of practical solutions to landfill problems. The nature of anthropogenic deposits and the spatial-temporal characteristics of leachates are reviewed in a geoelectrical context. The analogy between waste degradation and leaching, and the well-known weathering processes of supergene mineral enrichment and saprolite formation in crystalline rocks is explored, and used to develop a conceptual resistivity-vs.-depth model for landfill sites. The main tenet of the model is that vertical conductivity profiles will attain maximum values in the zone of mineral enrichment near the water table and tail-off away from it. This conceptual resistivity model is shown to be consistent with non-invasive observations in landfill sites in different geographical environments. Power-law relationships are found to exist between some geoelectrically important hydrochemical parameters (fluid conductivity, chloride content and total dissolved solids) in leachates and leachate-contaminated groundwater from some landfill sites. Since some chemical parameters of fill are known to vary consistently with time, a plausible hydrochemical and age-deductive scheme for saturated fill is proposed for geoelectrical models of landfills without significant amounts of metal. Practical suggestions are made for a consistent approach in geoelectrical investigation and diagnosis of old landfill sites. A few field examples are used to illustrate the diagnosis approach.

Meju, Maxwell A.



The routine and the traumatic in prenatal genetic diagnosis: does clinical information inform patient decision-making?  

Microsoft Academic Search

With the increasing technical sophistication of medicine, clinicians’ task of assuring patient informed consent is increasingly elusive. Taking the example of prenatal genetic testing, we examine efforts to communicate the complexities of genetic knowledge and risk calculation to patients. In this qualitative, descriptive study, we interviewed 50 clinicians and 40 patients, and observed 101 genetic counseling sessions. We found the

Linda M. Hunt; Katherine B. de Voogd; Heide Castañeda



Combined FISH and PRINS sperm analysis of complex chromosome rearrangement t(1;19;13): an approach facilitating PGD.  


Complex chromosome rearrangements (CCRs) are structural aberrations involving three or more breakpoints on two or more chromosomes. These CCRs result in a high rate of chromosome imbalances potentially leading to subfertility and congenital abnormality. In this study, we analysed meiotic segregation in the sperm of a patient with a familial CCR 46, XY,t(1;19;13)(p31;q13.2;q31)mat included in an intracytoplasmic sperm injection program because of oligoasthenozoospermia. The rearrangement was first identified using conventional and molecular cytogenetic methods. Primed in situ labelling (PRINS) and fluorescence in situ hybridization (FISH) techniques were then combined allowing the simultaneous use of five fluorochromes on the same sperm preparation, for the segregation analysis and the evaluation of the reproductive options for this patient. Segregation analysis was performed in a total of 1822 sperm nuclei from the translocation carrier. The percentage of unbalanced sperm was 75.9%, including 34.1% from 3:3 segregation, 38.2% from 4:2 segregation, 3.5% from 5:1 segregation and 0.05% from 6:0 segregation. Only 14.8% of sperm nuclei were consistent with a normal or balanced chromosome complement. In conclusion, chromosome segregation analysis combining FISH and PRINS was performed in sperm from a CCR carrier using five fluorochromes. These results advance our understanding of the mechanisms of meiotic segregation, and facilitate the assessment of the usefulness of preimplantation genetic diagnosis procedures in CCR couples. PMID:20019162

Loup, V; Bernicot, I; Janssens, P; Hedon, B; Hamamah, S; Pellestor, F; Anahory, T




NSDL National Science Digital Library

This activity helps students to understand basic principles of genetics, including relationships of genotype to phenotype, concepts of recessive and dominant alleles, and how understanding meiosis and fertilization provides the basis for understanding inheritance, as summarized in Punnett squares. The Student Handout includes an analysis of the inheritance of albinism that teaches all of these concepts, a Coin Toss Genetics activity that helps students understand the probabilistic nature of Punnett square predictions, and an analysis of the inheritance of sickle cell anemia that reinforces the basic concepts and introduces some of the complexities of genetics. The Genetics Supplement includes two additional activities, an analysis of student data on the sex makeup of sibships and pedigree analyses of recessive and dominant alleles with challenge questions that introduce the role of mutations and an evaluation of Punnett squares and pedigrees as models of inheritance.

Doherty, Jennifer; Waldron, Ingrid; Poethig, Scott


Targeted high-throughput sequencing for diagnosis of genetically heterogeneous diseases: efficient mutation detection in Bardet-Biedl and Alstr?m Syndromes  

PubMed Central

Background Bardet-Biedl syndrome (BBS) is a pleiotropic recessive disorder that belongs to the rapidly growing family of ciliopathies. It shares phenotypic traits with other ciliopathies, such as Alström syndrome (ALMS), nephronophthisis (NPHP) or Joubert syndrome. BBS mutations have been detected in 16 different genes (BBS1-BBS16) without clear genotype-to-phenotype correlation. This extensive genetic heterogeneity is a major concern for molecular diagnosis and genetic counselling. While various strategies have been recently proposed to optimise mutation detection, they either fail to detect mutations in a majority of patients or are time consuming and costly. Method We tested a targeted exon-capture strategy coupled with multiplexing and high-throughput sequencing on 52 patients: 14 with known mutations as proof-of-principle and 38 with no previously detected mutation. Thirty genes were targeted in total including the 16 BBS genes, the 12 known NPHP genes, the single ALMS gene ALMS1 and the proposed modifier CCDC28B. Results This strategy allowed the reliable detection of causative mutations (including homozygous/heterozygous exon deletions) in 68% of BBS patients without previous molecular diagnosis and in all proof-of-principle samples. Three probands carried homozygous truncating mutations in ALMS1 confirming the major phenotypic overlap between both disorders. The efficiency of detecting mutations in patients was positively correlated with their compliance with the classical BBS phenotype (mutations were identified in 81% of ‘classical’ BBS patients) suggesting that only a few true BBS genes remain to be identified. We illustrate some interpretation problems encountered due to the multiplicity of identified variants. Conclusion This strategy is highly efficient and cost effective for diseases with high genetic heterogeneity, and guarantees a quality of coverage in coding sequences of target genes suited for diagnosis purposes. PMID:22773737

Redin, Claire; Le Gras, Stephanie; Mhamdi, Oussema; Geoffroy, Veronique; Stoetzel, Corinne; Vincent, Marie-Claire; Chiurazzi, Pietro; Lacombe, Didier; Ouertani, Ines; Petit, Florence; Till, Marianne; Verloes, Alain; Jost, Bernard; Chaabouni, Habiba Bouhamed; Dollfus, Helene; Mandel, Jean-Louis; Muller, Jean



Oligonucleotide Arrays vs. Metaphase-Comparative Genomic Hybridisation and BAC Arrays for Single-Cell Analysis: First Applications to Preimplantation Genetic Diagnosis for Robertsonian Translocation Carriers  

PubMed Central

Comprehensive chromosome analysis techniques such as metaphase-Comparative Genomic Hybridisation (CGH) and array-CGH are available for single-cell analysis. However, while metaphase-CGH and BAC array-CGH have been widely used for Preimplantation Genetic Diagnosis, oligonucleotide array-CGH has not been used in an extensive way. A comparison between oligonucleotide array-CGH and metaphase-CGH has been performed analysing 15 single fibroblasts from aneuploid cell-lines and 18 single blastomeres from human cleavage-stage embryos. Afterwards, oligonucleotide array-CGH and BAC array-CGH were also compared analysing 16 single blastomeres from human cleavage-stage embryos. All three comprehensive analysis techniques provided broadly similar cytogenetic profiles; however, non-identical profiles appeared when extensive aneuploidies were present in a cell. Both array techniques provided an optimised analysis procedure and a higher resolution than metaphase-CGH. Moreover, oligonucleotide array-CGH was able to define extra segmental imbalances in 14.7% of the blastomeres and it better determined the specific unbalanced chromosome regions due to a higher resolution of the technique (?20 kb). Applicability of oligonucleotide array-CGH for Preimplantation Genetic Diagnosis has been demonstrated in two cases of Robertsonian translocation carriers 45,XY,der(13;14)(q10;q10). Transfer of euploid embryos was performed in both cases and pregnancy was achieved by one of the couples. This is the first time that an oligonucleotide array-CGH approach has been successfully applied to Preimplantation Genetic Diagnosis for balanced chromosome rearrangement carriers. PMID:25415307

Ramos, Laia; del Rey, Javier; Daina, Gemma; García-Aragonés, Manel; Armengol, Lluís; Fernandez-Encinas, Alba; Parriego, Mònica; Boada, Montserrat; Martinez-Passarell, Olga; Martorell, Maria Rosa; Casagran, Oriol; Benet, Jordi; Navarro, Joaquima




NSDL National Science Digital Library

What affects how physical characteristics are transmitted from parent to offspring? This is a question that can be answered at many levels. Molecular biologists examine the pattern of nucleotides in deoxyribonucleic acid (DNA) and the effect of mutations on the proteins produced. Classical geneticists explore the patterns by which traits are transmitted through families. Medical geneticists attempt to describe and develop treatments for diseases that have a genetic component. Genetic engineers analyze how traits can be altered in organisms through modern technology. These are only a few of the strategies that scientists employ to explain the nature of heredity. Explore historical perspectives on the study of genetics and investigate how cutting-edge technology is being used to expand our understanding of heredity.

National Science Teachers Association (NSTA)




NSDL National Science Digital Library

learning about our genetic make up We've been learning about DNA. Go to each web site, read and follow the instructions of the activities provided. On a piece of paper write your answers to the following questions and submit your work. Put the site for each of the questions you are answering. The first site is, ...

Curran, Carolyn



Führt uns die Präimplantationsdiagnostik auf eine Schiefe Ebene?  

Microsoft Academic Search

\\u000a Abstract.  \\u000a Definition of the problem: Preimplantation genetic diagnosis (PGD) is a new technique to test the in-vitro embryo for genetic disorders. Currently in\\u000a Germany a debate arises whether the use of PGD is ethically acceptable. Many authors emphasize that PGD might lead us on a\\u000a slippery slope towards the killing of persons, the creation of designer babies or the discrimination

Christian Netzer



Genetic architecture in bur oak, Quercus macrocarpa ( Fagaceae ), inferred by means of spatial autocorrelation analysis  

Microsoft Academic Search

Allozyme variation at seven putative polymorphic gene loci (Fle, Idh, Mdh-2, Mdh-3, 6 Pgd-2, Pgi-2, Pgm) was quantified in an isolatedQuercus macrocarpa population in northwestern Ontario, Canada. The bur oaks studied were slightly less genetically variable (He = 0.196,A = 3.43) than theQuercus subg.Lepidobalanus average. To assess the genetic differentiation within the topodeme,Moran's spatial autocorrelation coefficients were used for the

T. Geburek; P. Tripp-Knowles



Molecular genetic diagnosis of sickle cell disease using dried blood specimens on blotters used for newborn screening  

Microsoft Academic Search

Summary  The protein-based technologies used to screen newborns for sickle cell disease require confirmation with a liquid blood specimen.\\u000a We have developed a strategy for rapid and specific genotypic diagnosis using DNA extracted from a dried blood spot on the\\u000a filter paper blotter used to screen newborns. DNA could be microextracted from a specimen as small as a 1\\/8 inch diameter

David C. Jinks; Mikeanne Minter; Deborah A. Tarver; Mindy Vanderford; J. Fielding Hejtmancik; Edward R. B. McCabe



Redescription of Cercopithifilaria rugosicauda (Böhm & Supperer, 1953) (Spirurida: Onchocercidae) of roe deer, with an emended diagnosis of the genus Cercopithifilaria and a genetic characterisation.  


Newly collected material of Cercopithifilaria rugosicauda from roe deer Capreolus capreolus was analysed and compared to descriptions of C. rugosicauda from Austria and Hungary. The present specimens were assigned to the genus Cercopithifilaria using both morphological and molecular analyses. Complementary morphological data on the males and microfilariae of C. rugosicauda were described. The main morphological characters of different species of Cercopithifilaria were outlined and an emended generic diagnosis proposed. A genetic characterisation based on the analyses of cox1 and 12S rDNA sequences was reported supporting that C. rugosicauda was included in the clade of the genus Cercopithifilaria distinctly from other congeneric species available. However, these molecular analyses did not solve the relationships between the species of Cercopithifilaria. These could be approached using morphological characters that might be representative of their evolutionary history. In addition, Wolbachia was not seen in C. rugosicauda, either by immunohistological or by molecular approaches. PMID:25108130

Lefoulon, Emilie; Kuzmin, Yuri; Plantard, Olivier; Mutafchiev, Yasen; Otranto, Domenico; Martin, Coralie; Bain, Odile



Best practice guidelines for molecular genetic diagnosis of cystic fibrosis and CFTR-related disorders - updated European recommendations  

PubMed Central

The increasing number of laboratories offering molecular genetic analysis of the CFTR gene and the growing use of commercial kits strengthen the need for an update of previous best practice guidelines (published in 2000). The importance of organizing regional or national laboratory networks, to provide both primary and comprehensive CFTR mutation screening, is stressed. Current guidelines focus on strategies for dealing with increasingly complex situations of CFTR testing. Diagnostic flow charts now include testing in CFTR-related disorders and in fetal bowel anomalies. Emphasis is also placed on the need to consider ethnic or geographic origins of patients and individuals, on basic principles of risk calculation and on the importance of providing accurate laboratory reports. Finally, classification of CFTR mutations is reviewed, with regard to their relevance to pathogenicity and to genetic counselling. PMID:18685558

Dequeker, Els; Stuhrmann, Manfred; Morris, Michael A; Casals, Teresa; Castellani, Carlo; Claustres, Mireille; Cuppens, Harry; des Georges, Marie; Ferec, Claude; Macek, Milan; Pignatti, Pier-Franco; Scheffer, Hans; Schwartz, Marianne; Witt, Michal; Schwarz, Martin; Girodon, Emmanuelle



Novel Pancreatic Cancer Cell Lines Derived from Genetically Engineered Mouse Models of Spontaneous Pancreatic Adenocarcinoma: Applications in Diagnosis and Therapy  

PubMed Central

Pancreatic cancer (PC) remains one of the most lethal human malignancies with poor prognosis. Despite all advances in preclinical research, there have not been significant translation of novel therapies into the clinics. The development of genetically engineered mouse (GEM) models that produce spontaneous pancreatic adenocarcinoma (PDAC) have increased our understanding of the pathogenesis of the disease. Although these PDAC mouse models are ideal for studying potential therapies and specific genetic mutations, there is a need for developing syngeneic cell lines from these models. In this study, we describe the successful establishment and characterization of three cell lines derived from two (PDAC) mouse models. The cell line UN-KC-6141 was derived from a pancreatic tumor of a KrasG12D;Pdx1-Cre (KC) mouse at 50 weeks of age, whereas UN-KPC-960 and UN-KPC-961 cell lines were derived from pancreatic tumors of KrasG12D;Trp53R172H;Pdx1-Cre (KPC) mice at 17 weeks of age. The cancer mutations of these parent mice carried over to the daughter cell lines (i.e. KrasG12D mutation was observed in all three cell lines while Trp53 mutation was observed only in KPC cell lines). The cell lines showed typical cobblestone epithelial morphology in culture, and unlike the previously established mouse PDAC cell line Panc02, expressed the ductal marker CK19. Furthermore, these cell lines expressed the epithelial-mesenchymal markers E-cadherin and N-cadherin, and also, Muc1 and Muc4 mucins. In addition, these cell lines were resistant to the chemotherapeutic drug Gemcitabine. Their implantation in vivo produced subcutaneous as well as tumors in the pancreas (orthotopic). The genetic mutations in these cell lines mimic the genetic compendium of human PDAC, which make them valuable models with a high potential of translational relevance for examining diagnostic markers and therapeutic drugs. PMID:24278292

Souchek, Joshua J.; Mallya, Kavita; Johansson, Sonny L.; Batra, Surinder K.



Barren promise : the hope and heartache in treating infertility  

E-print Network

Preimplantation Genetic Diagnosis (PGD) is a reproductive medicine technology that allows the genetic characteristics of embryos to be examined. Created through in vitro fertilization, embryos are grown in a Petri dish for ...

McDonough, Maureen (Maureen Ann)



Pathologic diagnosis of large cell neuroendocrine carcinoma of the lung in an axillary lymph node: a case report with immunohistochemical and molecular genetic studies.  


The author herein reports a large cell neuroendocrine carcinoma (LCNEC) of the lung diagnosed in an axillary lymph node without clinical data, with an emphasis of KIT and PDGFRA. A 64-year-old woman presented with axillary and cervical lymph nodes swelling. An excisional biopsy of an axillary lymph node was performed under the clinical diagnosis of malignant lymphoma. The HE section showed a presence of large malignant cells arranged in a medullary pattern. The tumor cells had nucleoli. The HE diagnosis was large cell lymphoma or metastatic undifferentiated carcinoma, in particular large cell carcinoma of the lung. The tumor cells were positive for cytokeratins, p53 protein, thyroid transcriptional factor-1, neuron-specific enolase, synaptophysin, CD56, KIT, and PDGFRA. In contrast, they were negative for CD3, CD15, CD30, CD45, CD20, CD45RO, CEA, CA19-9, and chromogranin (Dako). Ki-67 labeling (Dako) was 100%. Therefore, a diagnosis of LCNEC of the lung was made. A molecular genetic analysis for KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) identified no mutations. Later, a lung tumor and pleural effusion were detected, and the cytology of the effusion and sputum revealed carcinoma cells compatible with LCNEC. The patient was diagnosed as lung LCNEC, and treated by chemotherapy (cisplatin) and radiation (45 Gray). The present report is the first one with an examination of protein expression and gene mutations of KIT and PDGFRA in a metastatic focus of LCNEC of the lung. PMID:23696939

Terada, Tadashi



Combined examination of sequence and copy number variations in human deafness genes improves diagnosis for cases of genetic deafness  

PubMed Central

Background Copy number variations (CNVs) are the major type of structural variation in the human genome, and are more common than DNA sequence variations in populations. CNVs are important factors for human genetic and phenotypic diversity. Many CNVs have been associated with either resistance to diseases or identified as the cause of diseases. Currently little is known about the role of CNVs in causing deafness. CNVs are currently not analyzed by conventional genetic analysis methods to study deafness. Here we detected both DNA sequence variations and CNVs affecting 80 genes known to be required for normal hearing. Methods Coding regions of the deafness genes were captured by a hybridization-based method and processed through the standard next-generation sequencing (NGS) protocol using the Illumina platform. Samples hybridized together in the same reaction were analyzed to obtain CNVs. A read depth based method was used to measure CNVs at the resolution of a single exon. Results were validated by the quantitative PCR (qPCR) based method. Results Among 79 sporadic cases clinically diagnosed with sensorineural hearing loss, we identified previously-reported disease-causing sequence mutations in 16 cases. In addition, we identified a total of 97 CNVs (72 CNV gains and 25 CNV losses) in 27 deafness genes. The CNVs included homozygous deletions which may directly give rise to deleterious effects on protein functions known to be essential for hearing, as well as heterozygous deletions and CNV gains compounded with sequence mutations in deafness genes that could potentially harm gene functions. Conclusions We studied how CNVs in known deafness genes may result in deafness. Data provided here served as a basis to explain how CNVs disrupt normal functions of deafness genes. These results may significantly expand our understanding about how various types of genetic mutations cause deafness in humans. PMID:25342930



New diagnosis of multiple myeloma in a patient with mantle cell lymphoma: Shared genetic factors or simple coincidence?  

PubMed Central

Multiple Myeloma and Mantle Cell Lymphoma are well defined hematological malignancies. Understanding of their pathogeneses has led to new therapies and increased survival. We report on a 64-yr-old female who was diagnosed with mantle cell lymphoma in 2003, then multiple myeloma in 2010. We identified only few other cases of concomitant MM and MCL. We also explored the importance of t(11;14)(q13;q32). The development of these two disorders in the same patient may simply be due to chance; however, it may also represent a common genetic hit affecting the B-cell population leading to development of two different malignancies. PMID:24371760

Sikuyayenga, Mutende J.; Reeder, Craig B.; Mikhael, Joseph R.



Do recent US Supreme Court rulings on patenting of genes and genetic diagnostics affect the practice of genetic screening and diagnosis in prenatal and reproductive care?  


Thousands of patents have been awarded that claim human gene sequences and their uses, and some have been challenged in court. In a recent high-profile case, Association for Molecular Pathology, et al. v. Myriad Genetics, Inc., et al., the US Supreme Court ruled that genes are natural occurring substances and therefore not patentable through 'composition of matter' claims. The consequences of this ruling will extend well beyond ending Myriad's monopoly over BRCA testing and may affect similar monopolies of other commercial laboratories for tests involving other genes. It could also simplify intellectual property issues surrounding genome-wide clinical sequencing, which can generate results for genes covered by intellectual property. Non-invasive prenatal testing (NIPT) for common aneuploidies using cell-free fetal (cff) DNA in maternal blood is currently offered through commercial laboratories and is also the subject of ongoing patent litigation. The recent Supreme Court decision in the Myriad case has already been invoked by a lower district court in NIPT litigation and resulted in invalidation of primary claims in a patent on currently marketed cffDNA-based testing for chromosomal aneuploidies. © 2014 John Wiley & Sons, Ltd. PMID:24989832

Chandrasekharan, Subhashini; McGuire, Amy L; Van den Veyver, Ignatia B



Prenatal diagnosis of spinal muscular atrophy: clinical experience and molecular genetics of SMN gene analysis in 36 cases  

PubMed Central

Summary Introduction prenatal diagnosis in families at risk for spinal muscular atrophy (SMA) mainly of type 1 is often applied due to the high incidence, most severe and newborn outcome of the disease. Case we present our clinical experience for 36 families with history of having at least one child with homozygous deletions of the SMN1 gene between. Seventeen families requested for prenatal prediction and of these cases, 8 fetuses were diagnosed to be at risk of developing the disease and the parents decided to terminate the pregnancy. Nine fetuses were detected with no homozygous deletion of the SMN1 and reached to full term delivery. Follow-up of live born children and abortion products never led to false or negative result. Conclusion therefore, application of SMN1 deletion detection by simple PCR assay in families with homozygous deletion of the SMN1 gene could be suggested for prenatal prediction in such families. PMID:24175014

Khaniani, Mahmoud Shekari; Derakhshan, Sima Mansoori; Abasalizadeh, Shamsei



Accurate and rapid novel genetic diagnosis for detection of sentinel lymph node metastasis in breast cancer patients  

PubMed Central

Background: The transcription-reverse transcription concerted reaction (TRC) test is a novel molecular-based procedure, which can assess nodal metastasis accurately and quickly. We examined the usefulness of the TRC test with a double marker, cytokeratin 19 (CK19) and carcinoembryonic antigen (CEA) mRNA, to detect sentinel lymph nodes (SLN) metastasis in breast cancer patients. Methods: A total of 264 SLNs from 131 breast cancer patients were assigned to a training set (109 SLNs from 50 patients) and validation set (155 SLNs from 81 patients). Cytokeratin 19 and CEA mRNA were detected by TRC tests, and the sensitivity and specificity of the SLN metastasis between the TRC and histology cohorts were compared. Results: Mean copy numbers of CK19 and CEA by TRC tests were increased according to the metastatic size. In the training set, TRC test showed 100% sensitivity, specificity and concordance rates against the permanent histopathology test. In the validation set, sensitivity was 97.1%, specificity was 99.2% and the concordance rate was 99.4%. Conclusion: Our results showed that the detection of CK19 and CEA mRNA using the TRC test is, an accurate and rapid method for detection of SLN metastasis and can be applied as an intraoperative molecular diagnosis in breast cancer patients. PMID:22782345

Iinuma, H; Tamura, J; Omoto, D; Kamo, N; Ohnaka, S; Mitoma, Y; Miyazawa, Y; Okinaga, K; Imamura, T; Fukushima, R; Watanabe, T; Ikeda, T



microRNA-18a is a genetic marker for the early diagnosis of cerebral injury induced by type 2 diabetes  

PubMed Central

The present study aimed to investigate the value of microRNA (miRNA)-18a for the early diagnosis of cerebral injury in patients with type 2 diabetes. Blood samples were collected from patients with type 2 diabetes, admitted to hospital between January and December 2013. The patients were randomly divided into three groups, which included one control and two experimental groups of severely and mildly diabetic patients (33 individuals per group). The levels of biochemical indicators in the serum, including S100 protein, neuron-specific enolase, myelin basic protein and endothelin-1, were determined. The mRNA and protein expression levels of hypoxia-inducible factor (HIF)-1? in the serum were measured by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. In addition, the serum expression levels of miRNA-18a were determined by qPCR. The concentrations of the biochemical indicators in the severe diabetes group were significantly higher compared with those from the other two groups. Furthermore, the mRNA and protein expression levels of HIF-1? in the severe diabetes group were significantly upregulated compared with the other groups. However, the levels of miRNA-18a in the severe diabetes group were significantly downregulated compared with the other groups. The present study demonstrated that the elevation of biochemical indicators in the serum and the upregulation of HIF-1? mRNA and protein expression are associated with the downregulation of miRNA-18a. Therefore, miRNA-18a may be a potential genetic marker for the early diagnosis of cerebral injury induced by type 2 diabetes. PMID:25371752




Genetics Home Reference: Hyperlysinemia  


... symptoms of the condition. Where can I find information about diagnosis or management of hyperlysinemia? These resources address the diagnosis or ... Genetic Testing Registry: Saccharopinuria You might also find information on the ... of hyperlysinemia in Educational resources and Patient support . ...


How Are Genetic Conditions Diagnosed?  


... facial features, can suggest the diagnosis of a genetic disorder. A geneticist will do a thorough physical examination ... and biochemical genetic testing are used to diagnose genetic disorders. Other laboratory tests that measure the levels of ...


Genetics Home Reference: Northern epilepsy  


... Recent literature OMIM Genetic disorder catalog Conditions > Northern epilepsy On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed September 2013 What is Northern epilepsy? Northern epilepsy is a genetic condition that causes ...


Genetics Home Reference: Narcolepsy  


... Genetic Testing Registry: Narcolepsy 5, susceptibility to Narcolepsy Network: Treatment You might also find information on the diagnosis or management of narcolepsy in Educational resources and Patient support . ...


Genetics Home Reference: Phenylketonuria  


... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Phenylketonuria On this page: Description Genetic changes Inheritance Diagnosis ... names Glossary definitions Reviewed February 2012 What is phenylketonuria? Phenylketonuria (commonly known as PKU) is an inherited ...


Genetics Home Reference: Neuroblastoma  


... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Neuroblastoma On this page: Description Genetic changes Inheritance Diagnosis ... names Glossary definitions Reviewed March 2011 What is neuroblastoma? Neuroblastoma is a type of cancer that most ...


Genetics Home Reference: Hemophilia  


... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Hemophilia On this page: Description Genetic changes Inheritance Diagnosis ... names Glossary definitions Reviewed August 2012 What is hemophilia? Hemophilia is a bleeding disorder that slows the ...


Genetic variation in cultivars of diploid ryegrass, Lolium perenne and L. multiflorum , at five enzyme systems  

Microsoft Academic Search

Samples of approximately 100 plants from each of 22 populations ofLolium perenne representing 15 cultivars, and from 13 populations ofLolium multiflorum representing six cultivars were scored for iso-zyme variants in five enzyme systems, PGI, GOT, ACP, PGM and 6-PGD. From the individual banding patterns a genetic interpretation of the variation was formulated and population studies of the resulting six polymorphic

H. Østergaard; G. Nielsen; H. Johansen



Malva sylvestris L. extract suppresses desferrioxamine-induced PGE? and PGD? release in differentiated U937 cells: the development and validation of an LC-MS/MS method for prostaglandin quantification.  


Malva sylvestris is a species used worldwide as an alternative to anti-inflammatory therapies; however, its mechanism of action remains unknown. In this paper, the anti-inflammatory effects of M. sylvestris alcoholic extracts were evaluated by measuring the pro-inflammatory mediators PGE? and PGD? in desferrioxamine-stimulated phorbol 12-myristate 13-acetate-differentiated U937 cells. An HPLC-DAD fingerprint of the M. sylvestris extract was performed and caffeic acid, ferulic acid and scopoletin were identified and quantified. An HPLC-MS/MS method was developed and validated to separate and measure the prostaglandins. The lower limits of detection (~0.5 ng/mL for PGE? and PGD?) and quantification (1.0 ng/mL for PGE? and PGD?) indicated that the method is highly sensitive. The calibration curves showed excellent coefficients of correlation (r > 0.99) over the range of 1.0-500.0 ng/mL, and at different levels, the accuracy ranged from 96.4 to 106.4% with an RSD < 10.0% for the precision study. This method was successfully applied using U937-d cells. A significant dose-dependent reduction of PGE2 and PGD2 levels occurred using 10 µg/mL (10.74 ± 2.86 and 9.60 ± 6.89%) and 50 µg/mL of extract (48.37 ± 3.24 and 53.06 ± 6.15%), suggesting that the anti-inflammatory mechanisms evoked by M. sylvestris may be related to modulation of these mediators. PMID:24403179

Martins, Cleverson Antonio Ferreira; Weffort-Santos, Almeriane Maria; Gasparetto, João Cleverson; Trindade, Angela Cristina Leal Badaró; Otuki, Michel Fleith; Pontarolo, Roberto



Scabies Diagnosis  


... . Parasites - Scabies Parasites Home Share Compartir Diagnosis Diagnosis of a scabies infestation usually is made based ... and the presence of burrows. Whenever possible, the diagnosis of scabies should be confirmed by identifying the ...


Genetics Home Reference: Familial dilated cardiomyopathy  


... studies OMIM Genetic disorder catalog Conditions > Familial dilated cardiomyopathy On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed December 2013 What is familial dilated cardiomyopathy? Familial dilated cardiomyopathy is a genetic form of ...


Genetics Home Reference: Familial restrictive cardiomyopathy  


... studies OMIM Genetic disorder catalog Conditions > Familial restrictive cardiomyopathy On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed January 2011 What is familial restrictive cardiomyopathy? Familial restrictive cardiomyopathy is a genetic form of ...


Genetics Home Reference: Czech dysplasia  


... Recent literature OMIM Genetic disorder catalog Conditions > Czech dysplasia On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed July 2008 What is Czech dysplasia? Czech dysplasia is an inherited condition that affects ...


Genetics Home Reference: Geleophysic dysplasia  


... Recent literature OMIM Genetic disorder catalog Conditions > Geleophysic dysplasia On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed December 2009 What is geleophysic dysplasia? Geleophysic dysplasia is an inherited condition that affects ...


Genetics Home Reference: Cleidocranial dysplasia  


... Recent literature OMIM Genetic disorder catalog Conditions > Cleidocranial dysplasia On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed January 2008 What is cleidocranial dysplasia? Cleidocranial dysplasia is a condition that primarily affects ...


Genetics Home Reference: Campomelic dysplasia  


... Recent literature OMIM Genetic disorder catalog Conditions > Campomelic dysplasia On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed June 2014 What is campomelic dysplasia? Campomelic dysplasia is a severe disorder that affects ...


Genetics Home Reference: Osteoglophonic dysplasia  


... Recent literature OMIM Genetic disorder catalog Conditions > Osteoglophonic dysplasia On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed July 2013 What is osteoglophonic dysplasia? Osteoglophonic dysplasia is a condition characterized by abnormal ...


Genetics Home Reference: Thanatophoric dysplasia  


... Recent literature OMIM Genetic disorder catalog Conditions > Thanatophoric dysplasia On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed October 2012 What is thanatophoric dysplasia? Thanatophoric dysplasia is a severe skeletal disorder characterized ...


Genetics Home Reference: Kniest dysplasia  


... Recent literature OMIM Genetic disorder catalog Conditions > Kniest dysplasia On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed July 2008 What is Kniest dysplasia? Kniest dysplasia is a disorder of bone growth ...


Genetics Home Reference: Mandibuloacral dysplasia  


... Recent literature OMIM Genetic disorder catalog Conditions > Mandibuloacral dysplasia On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed August 2013 What is mandibuloacral dysplasia? Mandibuloacral dysplasia is a condition that causes a ...


Genetics Home Reference: Diastrophic dysplasia  


... Recent literature OMIM Genetic disorder catalog Conditions > Diastrophic dysplasia On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed February 2008 What is diastrophic dysplasia? Diastrophic dysplasia is a disorder of cartilage and ...


Genetics Home Reference: Boomerang dysplasia  


... Recent literature OMIM Genetic disorder catalog Conditions > Boomerang dysplasia On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed September 2011 What is boomerang dysplasia? Boomerang dysplasia is a disorder that affects the ...


Genetics Home Reference: Metatropic dysplasia  


... Recent literature OMIM Genetic disorder catalog Conditions > Metatropic dysplasia On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed April 2012 What is metatropic dysplasia? Metatropic dysplasia is a skeletal disorder characterized by ...


Genetics Home Reference: Greenberg dysplasia  


... Recent literature OMIM Genetic disorder catalog Conditions > Greenberg dysplasia On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed February 2012 What is Greenberg dysplasia? Greenberg dysplasia is a severe condition characterized by ...


Genetics Home Reference: Congenital hypothyroidism  


... Research studies OMIM Genetic disorder catalog Conditions > Congenital hypothyroidism On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed May 2006 What is congenital hypothyroidism? Congenital hypothyroidism is a condition that affects infants ...


Genetics Home Reference: Breast cancer  


... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Breast cancer On this page: Description Genetic changes Inheritance Diagnosis ... names Glossary definitions Reviewed August 2007 What is breast cancer? Breast cancer is a disease in which certain ...


Genetics Home Reference: Fanconi anemia  


... Recent literature OMIM Genetic disorder catalog Conditions > Fanconi anemia On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed January 2012 What is Fanconi anemia? Fanconi anemia is a condition that affects many ...


Complement-coated antibody-transfer (CCAT); serum IgA1 antibodies intercept and transport C4 and C3 fragments and preserve IgG1 deployment (PGD).  


In periodontal disease, IgG1 and IgA1 antibodies produced in situ deposit on antigens in the affected tissues. Thus, there is an interest in the effect of co-deposited IgA1 antibodies on complement activation by IgG1-immune complexes. In the present study, we first analyzed the effect of IgA1-immune complexes on complement using human IgA1 antibodies to dansyl (with dansylated human serum albumin serving as the immobilized antigen). It was observed that these IgA1-immune complexes when incubated for prolonged times with 33% human serum as a source of complement received C4b and C3b deposition. As C4b and C3b deposited on the IgA1 antibodies and on the antigenic surface, the complement-coated IgA1 antibodies departed. These fluid-phase complement-coated IgA1 antibodies were transferred to antigen-coated microtiter-ELISA plates, where they became bound to the antigens. Thus, the complement-coated IgA1 antibodies retained their antigen-binding function, especially as a proportion of their covalently bound C3b progressively degraded to iC3b and C3d. Genetically engineered carbohydrate-deficient mutant human IgA1 antibodies were used to assess the role of carbohydrate in accepting the C4b and C3b depositions, and these studies indicated that the carbohydrate on the Fc-region of IgA1 played a positive role. Another interesting finding generated by this study was that when IgA1 was co-deposited with IgG1 antibodies, and serum complement was added, the IgG1 antibodies tended to remain on the antigenic surface. The co-deposited IgA1 antibodies not only controlled (reduced) the rate of the consumption of the first component of complement (C1) and of classical complement pathway activation by IgG1-immune complexes (and therein reduced the rate of complement-mediated dissolution of the IgG1-immune complexes), but also the co-deposited IgA1 antibodies simultaneously intercepted/accepted C4b and C3b, then departed, as complement began to cover the antigenic surfaces. The process in which complement-coated IgA1 antibodies transferred to non-complement-coated antigens is termed complement-coated antibody-transfer/transport (CCAT). In this way, IgA1 antibodies extended the efficiency of the complement system by insuring the specific IgA1 antibody-mediated transport of the captured biologically active complement fragments to those antigens stimulating the IgA1 antibody response but not yet neutralized (completely coated) with complement. Simultaneously by impeding the rate of C1 consumption and by intercepting C4b and C3b, IgA1 antibodies slowed C4b and C3b deposition on the antigenic surface and on the co-deposited IgG1 antibodies. Thus, in the presence of ongoing complement activation, the deposition of serum IgA1 antibodies enabled the co-deposited IgG1 antibodies to better maintain their ability to interact with antigens. We termed this latter phenomenon, preservation of IgG antibody deployment (PGD). In summary, co-deposited IgA1 antibodies maximized the efficiency of the complement system, transported their covalently bound complement fragments to specific antigens and sustained the effective deployment of IgG1 antibodies directed to those same antigens. PMID:16199260

Boackle, Robert J; Nguyen, Quang L; Leite, Renata S; Yang, Xiaofeng; Vesely, Jana



Fabrication of 1-dimensional nanowires from genetically modified M13 phage through surfactant-mediated hybridization and the applications in medical diagnosis, energy devices, and catalysis  

E-print Network

Biological building blocks served as excellent templates for the preparation of various nano-materials due to their beneficial interactions at the molecular level. The bio-mineralization of genetically engineered M13 ...

Lee, Youjin



Dermatomyositis: Diagnosis  


... to Help MDA Search form Search Dermatomyositis (DM) Diagnosis As with other muscle diseases, a doctor diagnoses ... biopsy can enable the physician to pinpoint the diagnosis to a type of myositis. In DM, the ...


Polymyositis: Diagnosis  


... to Help MDA Search form Search Polymyositis (PM) Diagnosis As with other muscle diseases, a doctor diagnoses ... biopsy can enable the physician to pinpoint the diagnosis to a type of myositis. In PM, the ...


Carrier Diagnosis  


... Bleeding Symptoms Carrier Diagnosis When to Test for Carrier Status Family Planning and Pregnancy Conception Options Prenatal Diagnosis Fetal Sex Determination Labour and Delivery Treatment of Bleeding Quality of Life Resources Inhibitors ...


Population genetics and structure of Buryats from the Lake Baikal Region of Siberia.  


Genetic polymorphisms of blood groups, serum proteins, red cell enzymes, PTC tasting, and cerumen types are reported for five Mongoloid populations of Buryats from the Lake Baikal region of Siberia (Russia). These groups are characterized by relatively high frequencies of alleles ABO*B, RH*D, cerumen D, GC*1F, ACP1*B, ESD*2, and PGD*C. Significant genetic heterogeneity between populations was demonstrated for the loci RH, MN, cerumen, PGD, ABO, GC, GLO, TF, and PGM1. Genetic distance analyses using five loci revealed a lower level of genetic microdifferentiation within the Buryat populations compared with other native Siberian groups. The distribution of gene markers in Buryats is similar to that found in neighboring Central Asian groups, such as the Yakuts and the Mongols. Intrapopulational analyses of the five Buryat subdivisions, based on R matrix and rii, indicate that one of the subdivisions is reproductively more isolated than the others and that two of the communities have received considerable gene flow. A nonlinear relationship was demonstrated between geographic and genetic distances of Buryat population subdivisions. PMID:8262501

Novoradovsky, A G; Spitsyn, V A; Duggirala, R; Crawford, M H



[Genetic cholestasis].  


During the last 11 years, advances in molecular genetics have changed our approach to children with intrahepatic cholestasis. Progress in identification of mutated genes now allows genetic diagnosis for several forms of cholestasis previously grouped into PFIC (progressive familial intrahepatic cholestasis). Three distinct forms: PFIC1, PFIC2, and PFIC3 are the result of mutations in the ATP8B1, ABCB11, and ABCB4 genes. The diagnosis is supported on clinical, biochemical and histological features. The therapeutic goals in theses diseases are alleviate symptoms and improve quality of life. Inborn errors of bile acid synthesis represent a subset of familial intrahepatic cholestasis. Replacement therapy with ursodeoxycholic acid and cholic acid avoids progression of the liver injury. PMID:19753442

Ciocca, Mirta; Alvarez, Fernando



17b-Hydroxysteroid Dehydrogenase3 Deficiency: Diagnosis, Phenotypic Variability, Population Genetics, and Worldwide Distribution of Ancient and de Novo Mutations  

Microsoft Academic Search

b-Hydroxysteroid dehydrogenase-3 (17bHSD3) deficiency is an autosomal recessive form of male pseudohermaphroditism caused by mutations in the HSD17B3 gene. In a nationwide study on male pseudohermaphroditism among all pediatric endocrinol- ogists and clinical geneticists in The Netherlands, 18 17bHSD3- deficient index cases were identified, 12 of whom initially had received the tentative diagnosis androgen insensitivity syndrome (AIS). The phenotypes and



Genetic Screening  

PubMed Central

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

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



17Beta-hydroxysteroid dehydrogenase-3 deficiency: diagnosis, phenotypic variability, population genetics, and worldwide distribution of ancient and de novo mutations  

Microsoft Academic Search

17Beta-hydroxysteroid dehydrogenase-3 (17betaHSD3) deficiency is an\\u000a autosomal recessive form of male pseudohermaphroditism caused by mutations\\u000a in the HSD17B3 gene. In a nationwide study on male pseudohermaphroditism\\u000a among all pediatric endocrinologists and clinical geneticists in The\\u000a Netherlands, 18 17betaHSD3-deficient index cases were identified, 12 of\\u000a whom initially had received the tentative diagnosis androgen insensitivity\\u000a syndrome (AIS). The phenotypes and genotypes of

A. L. M. Boehmer; D. J. J. Halley; Ruiter de P. E; M. F. Niermeijer; S. Andersson; Jong de F. H; H. H. Bode; S. L. S. Drop; H. Kayserili; Vroede de M. A; C. Rodrigues; B. J. Otten; B. B. Mendonça; H. A. Delemarre-van de Waal; C. W. Rouwé; A. O. Brinkmann; L. A. Sandkuijl



The Impact of Advances in Molecular Genetic Pathology on the Classification, Diagnosis and Treatment of Selected Soft Tissue Tumors of the Head and Neck  

PubMed Central

Recent advances in molecular pathology have had a significant impact on the diagnosis, classification, and treatment of soft tissue tumors. The practical application of these discoveries promises to assist greatly in the evaluation and treatment of soft tissue neoplasms in the head and neck region—an area characterized by exceedingly complex anatomy that often restricts the ample sampling of lesions and complete surgical resection. This reviews details some ways in which molecular techniques have strengthened conventional diagnostic and management approaches to low-grade fibromyxoid sarcoma, angiomatoid (malignant) fibrous histiocytoma, and dermatofibrosarcoma protuberans, all of which may involve the head and neck region. PMID:20237992

Garcia, Joaquin J.



High Frequency of Copy Number Variations and Sequence Variants at CYP21A2 Locus: Implication for the Genetic Diagnosis of 21-Hydroxylase Deficiency  

PubMed Central

Background The systematic study of the human genome indicates that the inter-individual variability is greater than expected and it is not only related to sequence polymorphisms but also to gene copy number variants (CNVs). Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (21OHD) is the most common autosomal recessive disorder with a carrier frequency of 1?25 to 1?10. The gene that encodes 21-hydroxylase enzyme, CYP21A2, is considered to be one of the most polymorphic human genes. Copy number variations, such as deletions, which are severe mutations common in 21OHD patients, or gene duplications, which have been reported as rare events, have also been described. The correct characterization of 21OHD alleles is important for disease carrier detection and genetic counselling Methodology and Findings CYP21A2 genotyping by sequencing has been performed in a random sample of the Spanish population, where 144 individuals recruited from university students and employees of the hospital were studied. The frequency of CYP21A2 mutated alleles in our sample was 15.3% (77.3% were mild mutations, 9% were severe mutations and 13.6% were novel variants). Gene dosage assessment was also performed when CYP21A2 gene duplication was suspected. This analysis showed that 7% of individuals bore a chromosome with a duplicated CYP21A2 gene, where one of the copies was mutated. Conclusions As far as we know, the present study has shown the highest frequency of 21OHD carriers reported by a genotyping analysis. In addition, a high frequency of alleles with CYP21A2 duplications, which could be misinterpreted as 21OHD alleles, was found. Moreover, a high frequency of novel genetic variations with an unknown effect on 21-hydroxylase activity was also found. The high frequency of gene duplications, as well as novel variations, should be considered since they have an important involvement in carrier testing and genetic counseling. PMID:18478071

Parajes, Silvia; Quinteiro, Celsa; Dominguez, Fernando; Loidi, Lourdes



Dual diagnosis  

Microsoft Academic Search

Dual diagnosis in psychiatry and addiction refers to the presence of a substance use disorder coexisting with another major psychiatric disorder. This article reviews the prevalence and timing of occurrence of the various disorders and their combinations. The problems in diagnosis and management associated with these diagnoses are explored both from the point of view of the patient and of

Michael Finbar Sheehan; CAROLINE HAWKINGS



Dual diagnosis  

Microsoft Academic Search

Dual diagnosis denotes the co-occurrence of severe mental illness and substance use disorder. This contribution summarizes the literature on dual diagnosis by reviewing epidemiology, phenomenology, clinical correlates, assessment, treatment and current research. Epidemiological data from several countries show that substance abuse or dependence is common (approximately 50%) among persons disabled by severe mental disorders such as schizophrenia, bipolar disorder or

Robert E. Drake



Genetics Home Reference: Mucopolysaccharidosis type VII  


... Where can I find information about diagnosis or management of mucopolysaccharidosis type VII? These resources address the diagnosis or management of mucopolysaccharidosis type VII and may include treatment providers. Genetic Testing ...


Genetics Home Reference: CHST3-related skeletal dysplasia  


... OMIM Genetic disorder catalog Conditions > CHST3-related skeletal dysplasia On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed October 2012 What is CHST3-related skeletal dysplasia? CHST3 -related skeletal dysplasia is a genetic condition ...


Genetics Home Reference: Lennox-Gastaut syndrome  


... Genetic Testing Registry: Epileptic encephalopathy Lennox-Gastaut type National Institute of Neurological Disorders and Stroke: Diagnosis and Treatment of Epilepsy News Release: FDA Approves New Drug ...


Genetics Home Reference: Early-onset glaucoma  


... studies OMIM Genetic disorder catalog Conditions > Early-onset glaucoma On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed February 2009 What is early-onset glaucoma? Glaucoma is a group of eye disorders in ...


Genetics Home Reference: Optic atrophy type 1  


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Genetics Home Reference: Atelosteogenesis type 1  


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Genetics Home Reference: Distal arthrogryposis type 1  


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Genetics Home Reference: Otopalatodigital syndrome type 1  


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Genetics Home Reference: Giant axonal neuropathy  


... literature OMIM Genetic disorder catalog Conditions > Giant axonal neuropathy On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed October 2007 What is giant axonal neuropathy? Giant axonal neuropathy is an inherited condition involving ...


Genetics Home Reference: Langer mesomelic dysplasia  


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Genetics Home Reference: Multiple epiphyseal dysplasia  


... literature OMIM Genetic disorder catalog Conditions > Multiple epiphyseal dysplasia On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed February 2008 What is multiple epiphyseal dysplasia? Multiple epiphyseal dysplasia is a disorder of cartilage ...


Genetics Home Reference: Septo-optic dysplasia  


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Genetics Home Reference: Mitochondrial trifunctional protein deficiency  


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Genetics Home Reference: Bietti crystalline dystrophy  


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Genetics Home Reference: Sjögren-Larsson syndrome  


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Genetics Home Reference: Spastic paraplegia type 4  


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Genetics Home Reference: Congenital diaphragmatic hernia  


... literature OMIM Genetic disorder catalog Conditions > Congenital diaphragmatic hernia On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed September 2013 What is congenital diaphragmatic hernia? Congenital diaphragmatic hernia is a defect in the ...


Genetics Home Reference: Pyridoxine-dependent epilepsy  


... literature OMIM Genetic disorder catalog Conditions > Pyridoxine-dependent epilepsy On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed February 2013 What is pyridoxine-dependent epilepsy? Pyridoxine-dependent epilepsy is a condition that involves ...


Genetics Home Reference: Lafora progressive myoclonus epilepsy  


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Genetics Home Reference: Diamond-Blackfan anemia  


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Genetics Home Reference: Acute promyelocytic leukemia  


... literature OMIM Genetic disorder catalog Conditions > Acute promyelocytic leukemia On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed April 2011 What is acute promyelocytic leukemia? Acute promyelocytic leukemia is a form of acute ...


Genetics Home Reference: Atelosteogenesis type 3  


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Genetics Home Reference: Intrahepatic cholestasis of pregnancy  


... OMIM Genetic disorder catalog Conditions > Intrahepatic cholestasis of pregnancy On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed June 2012 What is intrahepatic cholestasis of pregnancy? Intrahepatic cholestasis of pregnancy is a liver disorder ...


PRENATAL DIAGNOSIS Prenat Diagn (2011)  

E-print Network

to address questions around the translation and use of non- invasive prenatal testing using cell-free fetal of comprehensive, non-invasive prenatal genetic testing (Lo et al., 1997). Over the past decade, innovativePRENATAL DIAGNOSIS Prenat Diagn (2011) Published online in Wiley Online Library (wileyonlinelibrary


Autoinflammatory syndromes: diagnosis and management  

Microsoft Academic Search

During the last decades the description of autoinflammatory syndromes induced great interest among the scientific community. Mainly rheumatologists, immunologists and pediatricians are involved in the discovery of etiopathogenesis of these syndromes and in the recognition of affected patients. In this paper we will discuss the most important clues of monogenic and non-genetic inflammatory syndromes to help pediatricians in the diagnosis

Sara De Sanctis; Manuela Nozzi; Marianna Del Torto; Alessandra Scardapane; Stefania Gaspari; Giuseppina de Michele; Luciana Breda; Francesco Chiarelli



An Interesting Prenatal Diagnosis: Double Aneuploidy  

PubMed Central

Double aneuploidy, the existence of two chromosomal abnormalities in the same individual, is a rare condition. Early diagnosis of this condition is important to offer termination of pregnancy in genetic counselling. Cytogenetic analysis with amniocentesis and ultrasound examination is valuable for diagnosis of double aneuploidy. In this report we present a case with the karyotype of 48XXY+21 diagnosed prenatally. PMID:24368953

Aydin, Cetin; Yalcin, Yakup; Sen Selim, Halime



[Cryptorchidism: diagnosis and treatment].  


Cryptorchidism corresponds to the extra-scrotal position of the testis, and can be found in 3% of the term newborns and 0.5 to 1.0% of adults. It is usually an isolated clinical feature, but in around 10% of the cases can be associated to hypothalamic-pituitary dysfunction and genetic or embryonic disorders. The presence of additional genital abnormalities, such as hypospadia or micropenis, increases the probability of the diagnosis of an intersex condition. Detailed description of the testicular anatomic position is essential to adequate diagnosis, treatment and prognostic evaluation. The diagnosis of cryptorchidism is made by clinical examination. The complementary exams, such as image analysis, add limited information on the diagnosis. Gonadotropins and testicular hormones measurement can be useful if the hypothalamic-pituitary-gonadal axis is activated, as observed during the first 6 months of life or during puberty. Clinical treatment is indicated in patients with retained testis or in severely retractile testis. In these cases, human chorionic gonadotropin is employed at a dose of 50 IU/kg/week for 6 consecutive weeks. Clinical treatment cannot be used in cases of confirmed inguinal hernia, varicocele or spermatic cord cysts. Surgical correction is indicated after failure of clinical treatment or for ectopic testes. The long-term prognosis of cryptorchidism seems to be related to the precocity of the therapy. Therefore, recognition and treatment of cryptorchid testes should be done during the first 2 years of life, potentially improving the risks of infertility and gonadal neoplasia. PMID:16544048

Longui, Carlos Alberto



Human prenatal diagnosis  

SciTech Connect

Advances in the field of prenatal diagnosis have been rapid during the past decade. Moreover, liberal use of birth control methods and restriction of family size have placed greater emphasis on optimum outcome of each pregnancy. There are many prenatal diagnostic techniques of proven value; the risks, including false negatives and false positives, are known. With the rapid proliferation of new and experimental techniques, many disorders are potential diagnosable or even treatable; however, risk factors are unknown and issues relating to quality control have not been resolved. These problems are readily appreciated in the dramatic new techniques involving recombinant DNA, chorion villus sampling, and fetal surgery. Unfortunately, clinicians may not appreciate the difficulties that may also be encountered in the more mundane prenatal diagnostic tests such as ultrasonography or enzymatic testing. The aim of this volume is to clarify and rationalize certain aspects of diagnosis, genetic counseling, and intervention. New and experimental techniques are presented in the light of current knowledge.

Filkins, K.; Russo, J.F.



Jewish bioethics and medical genetics  

Microsoft Academic Search

Man has been aware of the science of genetics, i.e, how living things transport heritable traits to their offspring, since\\u000a biblical times. However, knowledge regarding genetic disorders has increased greatly in recent years. Advances have been made\\u000a with respect to both the methodology of genetic diagnosis and the treatment of genetic diseases. Both Jewish and secular ethicists,\\u000a in general, approve

Elliott Perlin



Diagnostic exome sequencing identifies two novel IQSEC2 mutations associated with X-linked intellectual disability with seizures: implications for genetic counseling and clinical diagnosis.  


Intellectual disability is a heterogeneous disorder with a wide phenotypic spectrum. Over 1,700 OMIM genes have been associated with this condition, many of which reside on the X-chromosome. The IQSEC2 gene is located on chromosome Xp11.22 and is known to play a significant role in the maintenance and homeostasis of the brain. Mutations in IQSEC2 have been historically associated with nonsyndromic X-linked intellectual disability. Case reports of affected probands show phenotypic overlap with conditions associated with pathogenic MECP2, FOXG1, CDKL5, and MEF2C gene mutations. Affected individuals, however, have also been identified as presenting with additional clinical features including seizures, autistic-behavior, psychiatric problems, and delayed language skills. To our knowledge, only 5 deleterious mutations and 2 intragenic duplications have been previously reported in IQSEC2. Here we report two novel IQSEC2 de novo truncating mutations identified through diagnostic exome sequencing in two severely affected unrelated male probands manifesting developmental delay, seizures, hypotonia, plagiocephaly, and abnormal MRI findings. Overall, diagnostic exome sequencing established a molecular diagnosis for two patients in whom traditional testing methods were uninformative while expanding on the mutational and phenotypic spectrum. In addition, our data suggests that IQSEC2 may be more common than previously appreciated, accounting for approximately 9 % (2/22) of positive findings among patients with seizures referred for diagnostic exome sequencing. Further, these data supports recently published data suggesting that IQSEC2 plays a more significant role in the development of X-linked intellectual disability with seizures than previously anticipated. PMID:24306141

Gandomi, Stephanie K; Farwell Gonzalez, K D; Parra, M; Shahmirzadi, L; Mancuso, J; Pichurin, P; Temme, R; Dugan, S; Zeng, W; Tang, Sha



Dual Diagnosis  

Microsoft Academic Search

It is estimated that 10 million persons in me United States have at least one mental disorder and at least one substance-related disorder in any given year. Dual disorders are common in psychiatry, but misdiagnosis may be even more common. Drug and alcohol testing should be expanded from routine use in the Olympics and intercollegiate athletics to psychiatric diagnosis of

Mark S. Gold



Genetics of anxiety disorders  

Microsoft Academic Search

There is considerable evidence that genetic determinants play a major role in the etiology of anxiety. Investigations into\\u000a susceptibility genes for anxiety are well underway, particularly for panic disorder and obsessive-compulsive disorder and\\u000a more broadly defined anxiety-related traits, such as neuroticism and harm avoidance. This review will discuss some of the\\u000a core issues related to diagnosis and molecular genetic methodology,

Paul D. Arnold; Gwyneth Zai; Margaret A. Richter



Melanoma Diagnosis  

NASA Astrophysics Data System (ADS)

The chapter deals with the diagnosis of the malignant melanoma of the skin. This aggressive type of cancer with steadily growing incidence in white populations can hundred percent be cured if it is detected in an early stage. Imaging techniques, in particular dermoscopy, have contributed significantly to improvement of diagnostic accuracy in clinical settings, achieving sensitivities for melanoma experts of beyond 95% at specificities of 90% and more. Automatic computer analysis of dermoscopy images has, in preliminary studies, achieved classification rates comparable to those of experts. However, the diagnosis of melanoma requires a lot of training and experience, and at the time being, average numbers of lesions excised per histology-proven melanoma are around 30, a number which clearly is too high. Further improvements in computer dermoscopy systems and their competent use in clinical settings certainly have the potential to support efforts of improving this situation. In the chapter, medical basics, current state of melanoma diagnosis, image analysis methods, commercial dermoscopy systems, evaluation of systems, and methods and future directions are presented.

Horsch, Alexander


Autoinflammatory syndromes: diagnosis and management.  


During the last decades the description of autoinflammatory syndromes induced great interest among the scientific community. Mainly rheumatologists, immunologists and pediatricians are involved in the discovery of etiopathogenesis of these syndromes and in the recognition of affected patients. In this paper we will discuss the most important clues of monogenic and non-genetic inflammatory syndromes to help pediatricians in the diagnosis and treatment of these diseases. PMID:20813071

De Sanctis, Sara; Nozzi, Manuela; Del Torto, Marianna; Scardapane, Alessandra; Gaspari, Stefania; de Michele, Giuseppina; Breda, Luciana; Chiarelli, Francesco



Autoinflammatory syndromes: diagnosis and management  

PubMed Central

During the last decades the description of autoinflammatory syndromes induced great interest among the scientific community. Mainly rheumatologists, immunologists and pediatricians are involved in the discovery of etiopathogenesis of these syndromes and in the recognition of affected patients. In this paper we will discuss the most important clues of monogenic and non-genetic inflammatory syndromes to help pediatricians in the diagnosis and treatment of these diseases. PMID:20813071



New Genetics  


... NIGMS Home > Science Education > The New Genetics The New Genetics Living Laboratories Classroom Poster Order a Free ... CRISPR Computing Genetics Model Organisms RNA Interference The New Genetics is a science education booklet explains the ...


Genetics Home Reference: Hereditary sensory neuropathy type 1  


... Genetic disorder catalog Conditions > Hereditary sensory neuropathy type 1 On this page: Description Genetic changes Inheritance Diagnosis ... December 2009 What is hereditary sensory neuropathy type 1? Hereditary sensory neuropathy type 1 is a condition ...


Genetics Home Reference: X-linked chondrodysplasia punctata 1  


... Genetic disorder catalog Conditions > X-linked chondrodysplasia punctata 1 On this page: Description Genetic changes Inheritance Diagnosis ... November 2011 What is X-linked chondrodysplasia punctata 1? X-linked chondrodysplasia punctata 1 is a disorder ...


Genetics Home Reference: Leukocyte adhesion deficiency type 1  


... Genetic disorder catalog Conditions > Leukocyte adhesion deficiency type 1 On this page: Description Genetic changes Inheritance Diagnosis ... April 2014 What is leukocyte adhesion deficiency type 1? Leukocyte adhesion deficiency type 1 is a disorder ...


Genetics Home Reference: Schimke immuno-osseous dysplasia  


... OMIM Genetic disorder catalog Conditions > Schimke immuno-osseous dysplasia On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed November 2008 What is Schimke immuno-osseous dysplasia? Schimke immuno-osseous dysplasia is a condition characterized ...


Genetics Home Reference: SOST-related sclerosing bone dysplasia  


... Genetic disorder catalog Conditions > SOST-related sclerosing bone dysplasia On this page: Description Genetic changes Inheritance Diagnosis ... June 2009 What is SOST-related sclerosing bone dysplasia? SOST -related sclerosing bone dysplasia is a disorder ...


Genetics Home Reference: Malonyl-CoA decarboxylase deficiency  


... gov Research studies PubMed Recent literature OMIM Genetic disorder catalog Conditions > Malonyl-CoA decarboxylase deficiency On this page: Description Genetic changes Inheritance Diagnosis Additional information Other names Glossary definitions Reviewed January ...


Genetics Home Reference: Peroxisomal acyl-CoA oxidase deficiency  


... gov Research studies PubMed Recent literature OMIM Genetic disorder catalog Conditions > Peroxisomal acyl-CoA oxidase deficiency On this page: Description Genetic changes Inheritance Diagnosis Additional information Other names Glossary definitions Reviewed April ...


Genetics Home Reference: GRN-related frontotemporal dementia  


... OMIM Genetic disorder catalog Conditions > GRN-related frontotemporal dementia On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed September 2010 What is GRN-related frontotemporal dementia? GRN -related frontotemporal dementia is a progressive brain ...


Genetics Home Reference: Pyridoxal 5'-phosphate-dependent epilepsy  


... Genetic disorder catalog Conditions > Pyridoxal 5'-phosphate-dependent epilepsy On this page: Description Genetic changes Inheritance Diagnosis ... June 2008 What is pyridoxal 5'-phosphate-dependent epilepsy? Pyridoxal 5'-phosphate-dependent epilepsy is a condition ...


Genetics Home Reference: Myostatin-related muscle hypertrophy  


... OMIM Genetic disorder catalog Conditions > Myostatin-related muscle hypertrophy On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed December 2008 What is myostatin-related muscle hypertrophy? Myostatin-related muscle hypertrophy is a rare condition ...


Genetics Home Reference: X-linked sideroblastic anemia  


... OMIM Genetic disorder catalog Conditions > X-linked sideroblastic anemia On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed April 2009 What is X-linked sideroblastic anemia? X-linked sideroblastic anemia is an inherited disorder ...


Genetics Home Reference: Iron-refractory iron deficiency anemia  


... Genetic disorder catalog Conditions > Iron-refractory iron deficiency anemia On this page: Description Genetic changes Inheritance Diagnosis ... July 2014 What is iron-refractory iron deficiency anemia? Iron-refractory iron deficiency anemia is one of ...


Genetics Home Reference: DMD-associated dilated cardiomyopathy  


... OMIM Genetic disorder catalog Conditions > DMD-associated dilated cardiomyopathy On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed February 2012 What is DMD-associated dilated cardiomyopathy? DMD -associated dilated cardiomyopathy is a form of ...


Challenges in the diagnosis of Marfan syndrome.  


Marfan syndrome (MFS) is a multisystem disorder of connective tissue that is inherited in an autosomal dominant fashion, and results from mutations in the FBN1 gene on chromosome 15. Diagnosis is challenging as it requires definition of diverse clinical features and input from a variety of specialists. Genetic testing of FBN1 is time consuming, expensive and complex, and may not solve the diagnostic dilemma. Failure to make a diagnosis or making an inappropriate diagnosis of MFS has social, lifestyle and medical consequences for the individual as well as the family. PMID:16803443

Summers, Kim M; West, Jennifer A; Peterson, Madelyn M; Stark, Denis; McGill, James J; West, Malcolm J



Fine-scale genetic structure and clinal variation in silene acaulis despite high gene flow  


We investigated whether the distribution of genes reflects the patchy distribution of individuals of Silene acaulis on Pennsylvania Mountain in central Colorado. Five polymorphic protein loci were analysed using both F-statistics and spatial autocorrelation. Low thetaPOP (FST) indicated little genetic differentiation between populations approximately 1 km apart. This indicates high gene flow within our study site, perhaps as a result of long-distance pollen dispersal. Despite little differentiation between populations, there was clinal variation at the 6-Pgd-1 locus and significant within-population genetic structure (indicated by both thetaPATCH and spatial autocorrelation). We infer that this fine-scale genetic structure is the result of limited seed dispersal combined with genetic drift. The level of genetic structure varied markedly among populations, with the greatest genetic structure (highest Moran's I and thetaPATCH values) in two low-altitude, small, low-density populations. Intensive sampling such as used in this study may reveal similar patterns of fine-scale genetic differentiation in other patchily distributed plant species, particularly those with limited seed dispersal. PMID:10383684

Gehring; Delph



Genetic Algorithms and Genetic Linkage  

Microsoft Academic Search

This chapter provides a summary of fundamental materials on genetic algorithms. It presents definitions of genetic algorithm terms and briefly describes how a simple genetic algorithm works. Then, it introduces the term genetic linkage and the so-called linkage problem that exists in common genetic algorithm practice. The importance of genetic linkage is often overlooked, and this chapter helps explain why

Ying-ping Chen


Genetics for the ophthalmologist  

PubMed Central

The eye has played a major role in human genomics including gene therapy. It is the fourth most common organ system after integument (skin, hair and nails), nervous system, and musculoskeletal system to be involved in genetic disorders. The eye is involved in single gene disorders and those caused by multifactorial etiology. Retinoblastoma was the first human cancer gene to be cloned. Leber hereditary optic neuropathy was the first mitochondrial disorder described. X-Linked red-green color deficiency was the first X-linked disorder described. The eye, unlike any other body organ, allows directly visualization of genetic phenomena such as skewed X-inactivation in the fundus of a female carrier of ocular albinism. Basic concepts of genetics and their application to clinical ophthalmological practice are important not only in making a precise diagnosis and appropriate referral, but also in management and genetic counseling. PMID:23439654

Sadagopan, Karthikeyan A.; Capasso, Jenina; Levin, Alex V.



Diabetic Retinopathy Diagnosis  


... Disorders > Diabetic Retinopathy > Diabetic Retinopathy Diagnosis Diabetic Retinopathy Diagnosis Diagnosing Diabetic Retinopathy You've come a long ... no better than 50/50. Today, the same diagnosis gives you a 90% chance of saving your ...


Diagnosis and evaluation of hypogonadism.  


Hypogonadism is defined as defects in gonadal response to gonadotropins or sex hormone biosynthesis. Clinical evaluation and diagnosis of patients is challenging, particularly before puberty. Basal determinations of the gonadotropins luteinizing hormone, follicle-stimulating hormone, the gonadal sex steroids testosterone and/or estrogen and markers of gonadal function including inhibin B and anti-Müllerian hormone are useful, but only at specific ages, thus necessitating combined hormonal tests with meticulous physical examination. GnRH testing can be useful, and may be used in combination with hCG testing to discriminate between isolated hypogonadotropic hypogonadism and constitutional delay of growth and puberty. Urine steroid profiles may be helpful in the diagnosis of androgen biosynthetic defects. Also increasingly important is genotypic screening for genetic or chromosomal abnormalities, together with detailed family and medical histories including antecedent substance abuse, chronic disease, and exposure to chemotherapy or radiotherapy. This chapter explores the diagnosis and evaluation of patients with hypogonadism and reviews the genetic/chromosomal factors involved in the condition. PMID:24683946

McCabe, Mark J; Bancalari, Rodrigo E; Dattani, Mehul T



[Genetic differentiation in plants of the genus Cypripedium from Russia inferred from allozyme data].  


Ten gene loci of nine enzyme systems (PGI, 6-PGD, NADHD, SKDH, GDH, PGM, DIA, ADH, GOT-1, and GOT-2) were analyzed in Cypripedium calceolus, C. macranthon, C. shanxiense, and C. ventricosum plants from the south of the Russian Far East. Alleles of loci 6-PGD, NADHD, GDH, ADH, GOT-1, and PGIproved to be diagnostic for C. calceolus and C. macranthon. Plants of C. shanxiense from Primorye and Sakhalin Island were monomorphic at all of the loci examined, and their allelic structure can be regarded as diagnostic for the species. The allelic structure for fragments of the C. calceolus population from the western and eastern parts of the species range differed in two loci, PGl and SKDH: alleles absent in C. calceolus plants from the western part of the range occurred at a high frequency in the plants of this species from the eastern part of the range (28 and 55 plants or 41% and 68%, respectively). These alleles were found in C. shanxiense. The genetic structure of C. shanxiense was similar to that of C. calceolus from the eastern part of the range, i.e., the region when these species are sympartic. The additional alleles in C. calceolus from the eastern part of the range might have appeared as a result of hybridization with C. shanxiense. Our results indicate that C. calceolus plants occuring on the territory of Russia form two groups that represent two different units of genetic diversity preservation. We suggest that C. x ventricosum plants in southern Primorye were formed by hybridization between C. macranthon and C. calceolus x C. shanxiense hybrids. Thus, they differ from plants inhabiting the Urals and West Siberia, which originated by hybridization between C. macranthon and C. calceolus. The population of C. x ventricosum presumably also consists of two plant groups differing in genetic structure, which should be regarded as two different units of preservation of this taxon. PMID:21786667

Filippov, E G; Andronova, E V



Human herpesvirus infections: Pathogenesis, diagnosis, and treatment  

SciTech Connect

This book contains 24 selections. Some of the titles are: Molecular Biology of Latent HSV-1; Molecular Genetics of Antiviral Chemotherapy of Herpes Viruses; Molecular Basis of Foscarnet Action; Use of Vaccinia Virus as a Vector for Expression of Herpesvirus Genes; and Diagnosis of Herpesvirus with Monoclonal Antibodies.

Lopez, C.; Roizman, B.



Biological substrates underpinning diagnosis of major depression  

E-print Network

Biological substrates underpinning diagnosis of major depression Etienne Sibille1,2 and Beverly, University of Pittsburgh, PA, USA Abstract Major depression is characterized by low mood, a reduced ability for complex illnesses. Indeed, genetic, molecular and cellular findings in major depression suggest shared

Sibille, Etienne


PRENATAL DIAGNOSIS Prenat Diagn 2002; 22: 11301134.  

E-print Network

PRENATAL DIAGNOSIS Prenat Diagn 2002; 22: 1130­1134. Published online in Wiley InterScience (www presented here provide the first single-cell genetic assay for Tay-Sachs disease based on real-time PCR attempted tests and an efficiency of 97%, as 7 of the 235 samples were excluded from further analysis

Wangh, Lawrence J.


Genetic algorithms  

NASA Technical Reports Server (NTRS)

Genetic algorithms are mathematical, highly parallel, adaptive search procedures (i.e., problem solving methods) based loosely on the processes of natural genetics and Darwinian survival of the fittest. Basic genetic algorithms concepts are introduced, genetic algorithm applications are introduced, and results are presented from a project to develop a software tool that will enable the widespread use of genetic algorithm technology.

Wang, Lui; Bayer, Steven E.



Noninvasive prenatal diagnosis: pregnant women's interest and expected uptake  

E-print Network

this testing. As such, adequate discussion of the implications of prenatal diagnostic testing will be critical. Copyright © 2011 John Wiley & Sons, Ltd. KEY WORDS: prenatal testing; noninvasive prenatal diagnosis prenatal diagnosis (NIPD) would allow fetal genetic testing through a sample of the mother's blood


Genetic Counseling  


Genetic counseling provides information and support to people who have, or may be at risk for, genetic disorders. A ... meets with you to discuss genetic risks. The counseling may be for yourself or a family member. ...


Osteogenesis imperfecta: diagnosis and treatment.  


Osteogenesis imperfecta (OI) is a genetic bone fragility disorder characterized by low bone mass, skeletal deformity, and variable short stature. OI is predominantly caused by dominant mutations affecting type 1 collagen synthesis, with a number of other genes implicated in OI over recent years. The clinical severity of OI can vary greatly, even within families who share a common mutation. Optimal management of OI requires a multidisciplinary approach involving pediatrician, endocrinologist (bone and mineral physician), rehabilitation specialist, orthopedic surgeon, dentist, geneticist, social worker/psychologist, physiotherapist, and occupational therapist. Bisphosphonate therapy remains the mainstay of medical treatment in OI and has been shown to decrease bone pain, enhance well-being, improve muscle strength and mobility and decrease fracture incidence. Novel therapies are beginning to emerge as more is understood about the signaling pathways involved in bone formation. The following summarizes the diagnosis, genetic heterogeneity and management of OI in pediatric practice. PMID:24964776

Biggin, A; Munns, C F




E-print Network

BREAST CANCER DETECTION USING GENETIC PROGRAMMING Hong Guo, Qing Zhang and Asoke K. Nandi, Feature Extraction, Classification, Breast Cancer Diagnosis. Abstract: Breast cancer diagnosis have been investigated by different machine learning methods. This paper proposes a new method for breast cancer

Fernandez, Thomas


Parental Choices and Ethical Dilemmas Involving Disabilities: Special Education and the Problem of Deliberately Chosen Disabilities  

ERIC Educational Resources Information Center

Ethical issues regarding children with disabilities have long involved their treatment after they are born. These issues remain important, but children may be deliberately created with or without characteristics that are usually thought of as disabilities. Preimplantation genetic diagnosis (PGD) and related technologies that involve human…

Kauffman, James M.; Hallahan, Daniel P.



Human embryonic stem cell lines derived from single blastomeres  

Microsoft Academic Search

The derivation of human embryonic stem (hES) cells currently requires the destruction of ex utero embryos. A previous study in mice indicates that it might be possible to generate embryonic stem (ES) cells using a single-cell biopsy similar to that used in preimplantation genetic diagnosis (PGD), which does not interfere with the embryo's developmental potential. By growing the single blastomere

Irina Klimanskaya; Young Chung; Sandy Becker; Shi-Jiang Lu; Robert Lanza



Symbiotic relationships: saviour siblings, family rights and biomedicine.  


It is now possible to combine the use of preimplantation genetic diagnosis (PGD) and tissue matching to select an IVF embryo that will, after birth, be a compatible tissue donor for an existing individual. This article analyses the ethical issues and the regulatory frameworks that intersect around the creation of tissue compatible children. PMID:17058348

Bennett, Belinda



Designing babies: what the future holds  

Microsoft Academic Search

Advances in reproductive technology have opened new opportunities to avoid inherited diseases in offspring. The preimplantation genetic diagnosis (PGD) of human embryos permits those embryos carrying gene disorders or a non-diploid chromosome constitution to be identified. Numerous disease genes including those with a late onset have been identified and the conditions averted in children. Risks of abortion have been reduced,

Yury Verlinsky



Prenatal diagnosis in congenital contractural arachnodactyly.  


Congenital contractural arachnodactyly (CCA) is a heritable connective tissue disorder caused by defects in the gene encoding fibrillin-2 (FBN2). People with CCA typically have a marfanoid habitus, flexion contractures, severe kyphoscoliosis, abnormal pinnae, and muscular hypoplasia. Because of the relative infrequency of the syndrome and its generally mild to moderate severity, prenatal diagnosis had not previously been sought. Here we report prenatal diagnosis in a family with CCA. Because the course of the disease in the proband was rather severe, she had requested genetic counseling as early as age 17. She delayed childbearing until prenatal diagnosis for CCA became possible. This decision was supported by her mother and later her husband. Because she shared the same genotype with her husband, genetic linkage analysis of this family did not alter the a priori 50% risk of having an affected child. The possibility of unambiguously ascertaining the affected status of a fetus homozygous for the tested FBN2 marker was sufficient for the family to pursue prenatal diagnosis. This case strongly points to the importance of informed decisions now that genetic testing is becoming commonplace. PMID:10464661

Belleh, S; Spooner, L; Allanson, J; Godfrey, M


Genetics of Age-Related Macular Degeneration  

Microsoft Academic Search

\\u000a Age-related Macular Degeneration (AMD) is a multifactorial disease involving genetic and environmental influences. Complement\\u000a Factor H (CFH) and HTRA1\\/LOC387715 are the two main loci associated with AMD. A genetic understanding of AMD may allow for\\u000a early diagnosis and treatment.

Daniel T. Kasuga; Yuhong Chen; Kang Zhang


Genetic counseling and ethical issues for autism  

Microsoft Academic Search

Exciting progress is being made in the journey toward discovery of genes conferring risk for autism and autism spectrum disorders. Currently, genetic counseling for idiopathic autism rests on clinical diagnosis and empiric risk estimates. While no genetic test for risk of autism currently exists, it is possible that such a test may emerge in the near future, and that commercial

William M. McMahon; Bonnie Jeanne Baty; Jeffrey Botkin



Diagnosis of endocrine disease: Biochemical diagnosis of phaeochromocytoma and paraganglioma.  


Adrenal phaechromocytomas and extra-adrenal sympathetic paragangliomas (PPGLs) are rare neuroendocrine tumours, characterised by production of the catecholamines: noradrenaline, adrenaline and dopamine. Tumoural secretion of catecholamines determines their clinical presentation which is highly variable among patients. Up to 10-15% of patients present entirely asymptomatic and in 5% of all adrenal incidentalomas a PPGL is found. Therefore, prompt diagnosis of PPGL remains a challenge for every clinician. Early consideration of the presence of a PPGL is of utmost importance, because missing the diagnosis can be devastating due to potential lethal cardiovascular complications of disease. First step in diagnosis is proper biochemical analysis to confirm or refute the presence of excess production of catecholamines or their metabolites. Biochemical testing is not only indicated in symptomatic patients but also in asymptomatic patients with adrenal incidentalomas or identified genetic predispositions. Measurements of metanephrines in plasma or urine offer the best diagnostic performance and are the tests of first choice. Paying attention to sampling conditions, patient preparation and use of interfering medications is important, as these factors can largely influence test results. When initial test results are inconclusive, additional tests can be performed, such as the clonidine suppression test. Test results can also be used for estimation of tumour size or prediction of tumour location and underlying genotype. Furthermore, tumoural production of 3-methoxytyramine is associated with presence of an underlying SDHB mutation and may be a biomarker of malignancy. PMID:24347425

van Berkel, A; Lenders, J W M; Timmers, H J L M



Risks of reproducing with a genetic disorder.  


Male-factor infertility is the cause of reproductive issues in many couples. For approximately 15% of these men, the origin of the infertility is genetic. These causes include both chromosomal and single-gene disorders frequently impacting spermatogenesis. By identifying the genetic mechanism behind the infertility, we determine the ability of the couple to use assisted reproduction technologies. Use of these methods has ignited a new spectrum of concerns for the genetic competence of the offspring. By knowing what specific genetic risks exist for the offspring of men with these particular disorders, we are able to use preimplantation genetic diagnosis to detect these problems. PMID:23775381

Byler, Melissa Ciano; Lebel, Robert Roger



Genetic modification and genetic determinism  

Microsoft Academic Search

In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and

David B. Resnik; Daniel B. Vorhaus



Apolipoprotein E Genotyping in the Diagnosis and Differential Diagnosis of Alzheimer's Disease  

Microsoft Academic Search

Background : There is a growing interest in the use of genetic markers in predicting the various types of dementia such as Alzheimer's disease (AD) and vascular dementia (VD). It is important to differentiate AD from other causes of dementia because the early diagnosis of AD or VD could lead to early therapeutic intervention. This study is to confirm the

Oh-Young Bang; Yong-Tae Kwak



Ethical dilemmas in clinical genetics  

Microsoft Academic Search

This paper discusses the results of a survey of medical and paramedical opinion relating to various difficult ethical issues in clinical genetics. These include the confidentiality of the doctor-patient relationship, prenatal diagnosis and termination, and Huntington's chorea. It is suggested that this method provides a useful means of assessing what is ethically acceptable in contemporary society.

I D Young



EEG and Autism Diagnosis  

MedlinePLUS Videos and Cool Tools

... hand corner of the player. EEG and Autism Diagnosis HealthDay September 24, 2014 Related MedlinePlus Page Autism ... 1 in 68 children has autism spectrum disorder. Diagnosis is currently based on behavioral characteristics and symptoms. ...


Diagnosis of Ataxia  


... Time (GMT) Donate to the National Ataxia Foundation Diagnosis of Ataxia Being diagnosed with Ataxia can be ... Ataxia Foundation's primary emphases. How is Ataxia Diagnosed? Diagnosis is based on a person's medical history, family ...


Communication of psychiatric diagnosis.  


We examined whether psychiatric patients knew their diagnosis, the significance they attached to it, and the impact of being informed in a systematic fashion according to their wishes. We also assessed whether the nature of the psychiatric diagnosis influenced what patients were told by their psychiatrists. The three parts of the study included questionnaire responses from 28 consultant psychiatrists: case-note reviews and questionnaire responses of 200 adult psychiatric in-patients: and a pilot study informing 28 adult psychiatric day hospital patients of their diagnosis according to their wishes. The results showed that of 126 in-patients, 53% had not been told their diagnosis, although most wanted to know. Of those informed, 75% agreed with their diagnosis. The majority of patients considered a psychiatric diagnosis to be as real as a physical diagnosis and helpful in their treatment. Patients with schizophrenia were less likely to have been informed of their diagnosis, and psychiatrists were also more reticent regarding the diagnosis of personality disorder. All patients who were systematically informed, in the pilot study agreed with their diagnosis. We conclude that most patients agree with their diagnosis and its usefulness. All patients should be asked whether they want to know their diagnosis and be informed appropriately. PMID:9448443

Shergill, S S; Barker, D; Greenberg, M



Parental attitudes toward genetic testing for prelingual deafness in China  

Microsoft Academic Search

ObjectiveRecent advances in molecular biology of hearing and deafness have made genetic testing an option for deaf individuals and their families. In China, DNA microarray and other genetic testing method has been applied to rapid genetic diagnosis of non-syndromic hearing loss. However, there is no information about the interests in such testing in China. The purpose of this study is

Siqing Fu; Jiashu Dong; Chunfang Wang; Guanming Chen



During the course of the Medical Genetics residency training program, each trainee must acquire an understanding of basic genetic principles and familiarity with all of the major  

E-print Network

or have a genetic component, (3) familiarity with the tests used in evaluation of genetic disorders will cover general medical genetics, dysmorphology and teratology, prenatal diagnosis and screening of the appropriate genetic testing laboratories. While the program will include enough flexibility to accommodate

Stephens, Matthew


[Is systemic diagnosis possible?].  


The authors discuss the concept of systemic diagnosis and its logical and scientific validity. A diagnosis is the result of the "diagnostic process", with the presence of the acting object (the person making the diagnosis) and the subject (the individual or group patient, such as family), between whom there is a skew relation. They also wonder, to which part of this diagnostic process is the term "systemic" applied--to the clinician or to the subject of the diagnosis, their relation or the effect of the process. The authors also stress the crucial effect of the constructivism and social constructionism on the process of the systemic diagnosis. PMID:18567400

Siewierska, Anna; Sliwczy?ska, Jadwiga; Namys?owska, Irena



Genetic modification and genetic determinism  

PubMed Central

In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884

Resnik, David B; Vorhaus, Daniel B



Consumerism in prenatal diagnosis: a challenge for ethical guidelines  

PubMed Central

The ethical guidelines for prenatal diagnosis proposed by the World Health Organisation (WHO), as well as by national regulations, only refer to paternity and gender of the fetus as unacceptable, disease-unrelated criteria for prenatal selection, as no other such parameters are at hand so far. This perspective is too narrow because research on complex genetic systems such as cognition and ageing is about to provide clinically applicable tests for genetic constituents of potentially desirable properties such as intelligence or longevity which could be misused as parameters for prenatal diagnosis. Moreover, there is an increasing number of prenatally testable genetic traits, such as heritable deafness, which are generally regarded as pathological but desired by some prospective parents and taken into account as parameters for pro-disability selection. To protect prenatal diagnosis from ethically unacceptable genetic consumerism, guidelines must be clarified as soon as possible and updated towards a worldwide restriction of prenatal genetic testing to immediately disease-determining traits. Key Words: Genetics • prenatal diagnosis • ethics • consumerism PMID:11129845

Henn, W.



Wissensverarbeitung Model Based Diagnosis-Model-Based Diagnosis -  

E-print Network

Wissensverarbeitung Model Based Diagnosis- Model-Based Diagnosis - Alexander Felfernig and Gerald Description (Model) Physical SystemDiagnosis Ob d B h iD i d B h i Di Observed BehaviorDesiered Behavior problems C t d ti Cost reduction -8- #12;Definitions 1 Diagnosis System:A diagnosis system1. Diagnosis


Genetic Screening  

NSDL National Science Digital Library

Many genetic disorders can be detected with tests of blood and chromosomes. Genetic screening is the large-scale use of these tests as part of the public health program. Different members of society, worldwide, have advocated genetic screening to achieve different goals. This chapter provides a critical analysis of this controversial issue.

Slesnick, Irwin



Imaging Genetics  

ERIC Educational Resources Information Center

Imaging genetics is an experimental strategy that integrates molecular genetics and neuroimaging technology to examine biological mechanisms that mediate differences in behavior and the risks for psychiatric disorder. The basic principles in imaging genetics and the development of the field are discussed.

Munoz, Karen E.; Hyde, Luke W.; Hariri, Ahmad R.



Copyright 0 1984 by the Genetics Society of America DEVELOPMENTAL GENETICS OF T H E 2E-F REGION OF  

E-print Network

-F area Rearrangement Cytology References Df1)Pgd kz Df1)Pgd 35 Df(1)64cl8 Df1)pn'" Df1)TEM 304 Df1)278.4B rearrangement are noted. a CRAYMERand ROY(1980) list the cytology of Df1)Pg~i'~as Df1)2D?-2F5; we believe

Perrimon, Norbert


Genetics Lab 3 Mendelian Genetics  

E-print Network

Genetics Lab 3 Mendelian Genetics Monohybrid, Dihybrid and Test crosses Mendel made bold (and was the first to describe "particulate unit factors" which control expression of specific traits. Mendel based, and his quantitative data served as the cornerstone of modern genetic discoveries. Mendel went


[Differential diagnosis of hearing disorders].  


Hearing impairment is considered as the most common impairment of a human sense system. According to WHO, 360 Million people worldwide were affected by hearing loss in 2012, out of which 91% were adults and 9% children.Hearing impairment can be triggered by various mechanisms, such as locally destructive processes (chronic otitis media, cholesteatoma or traumatic lesions) or systemic influences like infectious or ototoxic substances (measles, mumps, meningococcal meningitis or medication and industrial agents). Congenital dysplasia, perinatal complications and genetic modifications can lead to hearing loss as well. Moreover, the acute or chronic noise exposure associated with the changing spare time activities in industrial nations represents an increasingly significant source of hearing impairment. In order to achieve the best hearing rehabilita-tion, a specific differential diagnosis in each case is of significant importance. PMID:25302598

Schulze, A; Zahnert, T



Mitochondrial genetics and disease.  


Mitochondrial disease resulting in reduced bioenergetic output can be due to mutations in either nuclear DNA-encoded or mitochondrial DNA-encoded gene products. We summarize some of the underlying principles of mitochondrial genetics that impact the diagnosis and pathogenesis of mitochondrial disorders. In addition, we present a brief overview of a new frontier in the field, namely, mitochondrial "dynamics," which controls organellar fusion, fission, trafficking, and positioning, and exerts mitochondrial "quality control" by maintaining organellar integrity and viability. Analysis of mutations in gene products associated with this latter area has opened up new vistas in the study of disorders associated with compromised energy production. PMID:25028417

Area-Gomez, Estela; Schon, Eric A



Advances in human genetics  

SciTech Connect

This book has five chapters covering peroxisomal diseases, X-linked immunodeficiencies, genetic mutations affecting human lipoproteins and their receptors and enzymes, genetic aspects of cancer, and Gaucher disease. The chapter on peroxisomes covers their discovery, structure, functions, disorders, etc. The chapter on X-linked immunodeficiencies discusses such diseases as agammaglobulinemia, severe combined immunodeficiency, Wiskott-Aldrich syndrome, animal models, linkage analysis, etc. Apolipoprotein formation, synthesis, gene regulation, proteins, etc. are the main focus of chapter 3. The chapter on cancer covers such topics as oncogene mapping and the molecular characterization of some recessive oncogenes. Gaucher disease is covered from its diagnosis, classification, and prevention, to its organ system involvement and molecular biology.

Harris, H.; Hirschhorn, K. (eds.)



Recommendations for reporting results of diagnostic genetic testing (biochemical, cytogenetic and molecular genetic)  

PubMed Central

Genetic test results can have considerable importance for patients, their parents and more remote family members. Clinical therapy and surveillance, reproductive decisions and genetic diagnostics in family members, including prenatal diagnosis, are based on these results. The genetic test report should therefore provide a clear, concise, accurate, fully interpretative and authoritative answer to the clinical question. The need for harmonizing reporting practice of genetic tests has been recognised by the External Quality Assessment (EQA), providers and laboratories. The ESHG Genetic Services Quality Committee has produced reporting guidelines for the genetic disciplines (biochemical, cytogenetic and molecular genetic). These guidelines give assistance on report content, including the interpretation of results. Selected examples of genetic test reports for all three disciplines are provided in an annexe. PMID:23942201

Claustres, Mireille; Kozich, Viktor; Dequeker, Els; Fowler, Brain; Hehir-Kwa, Jayne Y; Miller, Konstantin; Oosterwijk, Cor; Peterlin, Borut; van Ravenswaaij-Arts, Conny; Zimmermann, Uwe; Zuffardi, Orsetta; Hastings, Ros J; Barton, David E



Preimplantation Genetic Testing: Indications and Controversies  

PubMed Central

Synopsis In the last two decades, the use of preimplantation genetic testing has increased dramatically. It is used for single gene disorders, chromosomal abnormalities, mitochondrial disorders, gender selection in non-Mendelian disorders with unequal gender distribution, aneuploidy screening, and other preconceptually identified genetic abnormalities in prospective parents. Genetic testing strategies and diagnostic accuracy continues to improve. Yet, it does not come without risks or controversies. In this review we discuss the techniques and clinical application of preimplantation genetic diagnosis and the debate surrounding its associated uncertainty and expanded use. PMID:20638568

Cooper, Amber R.; Jungheim, Emily S.



Scitable: Genetics  

NSDL National Science Digital Library

A free science library and personal learning tool brought to you by Nature Publishing Group, the world's leading publisher of science. Scitable currently concentrates on genetics, the study of evolution, variation, and the rich complexity of living organisms. As you cultivate your understanding of modern genetics on Scitable, you will explore not only what we know about genetics and the ways it impacts our society, but also the data and evidence that supports our knowledge.


Population Genetics  

Microsoft Academic Search

Understanding population genetics is critical to designing and interpreting results for human genetic studies. Much research\\u000a has been done in this area in the past century, often involving sophisticated mathematical and computational tools. However,\\u000a there has been a detachment between theoretical developments and real data analyses primarily due to the lack of data for\\u000a population genetics studies. The landscape has

Bruce Weir


Celiac disease diagnosis and gluten-free food analytical control  

Microsoft Academic Search

Celiac disease (CD) is an autoimmune enteropathy, characterized by an inappropriate T-cell-mediated immune response to the\\u000a ingestion of certain dietary cereal proteins in genetically susceptible individuals. This disorder presents environmental,\\u000a genetic, and immunological components. CD presents a prevalence of up to 1% in populations of European ancestry, yet a high\\u000a percentage of cases remain underdiagnosed. The diagnosis and treatment should

Marta Maria Pereira da Silva Neves; Maria Begoña González-Garcia; Hendrikus Petrus Antonius Nouws; Cristina Delerue-Matos; Alice Santos-Silva; Agustín Costa-García



Diagnosis of instrument fault  

Microsoft Academic Search

The diagnosis of faults in instrumentation equipment can often be confused with faults in the system. The correct diagnosis of instrument faults is of importance. Here it is described how to detect instrument faults in non-linearity. Time-varying processes that include uncertainties such as modelling error, parameter ambiguity, and input and output noise. The design of state estimation filters with zero

K. Watanabe; A. Komori; T. Kiyama



Rabies Diagnosis in Human  

Microsoft Academic Search

Rabies diagnosis in humans can be made by obtaining a history of exposure particularly to an animal bite, clinical symptoms and signs, neuroimaging such as magnetic resonance imaging (MRI) and laboratory testing. Although diagnosis made by clinical grounds alone can be useful, this can only be limited to furious rabies. Owing to the fact that there is more than one

Supaporn Wacharapluesadee


Computerized dermatopathologic diagnosis.  


A practical, transferable microcomputer system for differential diagnosis in dermatopathology, called TEGUMENT, has been developed for use by dermatologists on the standard IBM PC, Compaq, and other compatible personal microcomputers. In an interactive computer program a set of information is abstracted from the microscopic study of each specimen by a dermatologist, to compare with a structured knowledge base. The process leads through a relevant sequence of descriptive phrases until the findings can be allocated to a disease class. The microscopic description and diagnosis are then combined with clinical information by the computer and printed, optionally, as a pathology report. The identification and diagnosis of each case are preserved in permanent memory to enable future search and sorting. The results of independent validation are that a pathologist made the same diagnosis as the machine or a similar differential diagnosis in 91.8%, disagreed in 4.8%, and was unable to make a diagnosis from the description furnished by the machine in 3.4% of 147 actual cases. We conclude that a certain critical minimum of information is required for objective diagnosis; more information is needed for definitive than for differential diagnosis; a characteristic feature is necessary to distinguish between differential diagnoses; an objective description may admit of more than one diagnosis; ambiguity may be reduced by presenting for consideration all distinguishing features that characterize closely related diagnoses; and the personal microcomputer, programmed in this way, is of considerable assistance to the dermatologist in the histopathologic diagnosis of diseases and neoplasms of the skin. PMID:3301922

Potter, B; Ronan, S G



Genetics Home Reference: Spinal muscular atrophy with progressive myoclonic epilepsy  


... catalog Conditions > Spinal muscular atrophy with progressive myoclonic epilepsy On this page: Description Genetic changes Inheritance Diagnosis ... What is spinal muscular atrophy with progressive myoclonic epilepsy? Spinal muscular atrophy with progressive myoclonic epilepsy (SMA- ...


Genetics Home Reference: PDGFRB-associated chronic eosinophilic leukemia  


... PubMed Recent literature Conditions > PDGFRB-associated chronic eosinophilic leukemia On this page: Description Genetic changes Inheritance Diagnosis ... February 2013 What is PDGFRB-associated chronic eosinophilic leukemia? PDGFRB -associated chronic eosinophilic leukemia is a type ...


Genetics Home Reference: Cytogenetically normal acute myeloid leukemia  


... PubMed Recent literature Conditions > Cytogenetically normal acute myeloid leukemia On this page: Description Genetic changes Inheritance Diagnosis ... January 2014 What is cytogenetically normal acute myeloid leukemia? Cytogenetically normal acute myeloid leukemia (CN-AML) is ...


Genetic Research  

PubMed Central

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) was founded 40 years ago to help elucidate the biological underpinnings of alcohol dependence, including the potential contribution of genetic factors. Twin, adoption, and family studies conclusively demonstrated that genetic factors account for 50 to 60 percent of the variance in risk for developing alcoholism. Case–control studies and linkage analyses have helped identify DNA variants that contribute to increased risk, and the NIAAA-sponsored Collaborative Studies on Genetics of Alcoholism (COGA) has the expressed goal of identifying contributing genes using state-of-the-art genetic technologies. These efforts have ascertained several genes that may contribute to an increased risk of alcoholism, including certain variants encoding alcohol-metabolizing enzymes and neurotransmitter receptors. Genome-wide association studies allowing the analysis of millions of genetic markers located throughout the genome will enable discovery of further candidate genes. In addition to these human studies, genetic animal models of alcohol’s effects and alcohol use have greatly advanced our understanding of the genetic basis of alcoholism, resulting in the identification of quantitative trait loci and allowing for targeted manipulation of candidate genes. Novel research approaches—for example, into epigenetic mechanisms of gene regulation—also are under way and undoubtedly will further clarify the genetic basis of alcoholism. PMID:23579937

Foroud, Tatiana; Edenberg, Howard J.; Crabbe, John C.



Genetic Counseling.  

ERIC Educational Resources Information Center

Information is presented on a number of tests used in genetic counseling (e.g., genetic evaluation, chromosome evaluation, consideration of multifactorial conditions, prenatal testing, and chorionic villus sampling) which help parents with one disabled child make family planning decisions. (CB)

Exceptional Parent, 1987



Genetic Library  

Microsoft Academic Search

The first three articles of this Genetic Library are from a special issue of the Journal of Health Psychology , which is published in the UK. This particular issue is devoted to studies using interpretative phenomenological analysis(IPA) to examine several psychological and social issues in the “new genetics” (the clinical advances of the human genome project.) Its intended audience is

Martha D. MacMillin



Landscape Genetics  

NSDL National Science Digital Library

Landscape genetics is a rapidly evolving interdisciplinary field that integrates approaches from population genetics and landscape ecology. In the context of habitat fragmentation, the current focus of landscape genetics is on assessing the degree to which landscapes facilitate the movement of organisms (landscape connectivity) by relating gene-flow patterns to landscape structure. Neutral genetic variation among individuals or direct estimates of current gene flow are statistically related to landscape characteristics such as the presence of hypothesized barriers or the least-cost distance for an organism to move from one habitat patch to another, given the nature of the intervening matrix or habitat types. In the context of global change, a major challenge for landscape genetics is to address the spread of adaptive variation across landscapes. Genome scans combined with genetic sample collection along environmental gradients or in different habitat types attempt to identify molecular markers that are statistically related to specific environmental conditions, indicating adaptive genetic variation. The landscape genetics of adaptive variation may also help answer fundamental questions about the collective evolution of populations.

Rolf Holderegger (Swiss Federal Research Institute;); Helene H. Wagner (University of Toronto;)



Genetic Engineering  

ERIC Educational Resources Information Center

Presents a review of genetic engineering, in which the genotypes of plants and animals (including human genotypes) may be manipulated for the benefit of the human species. Discusses associated problems and solutions and provides an extensive bibliography of literature relating to genetic engineering. (JR)

Phillips, John



Advances in gene technology: Human genetic disorders  

SciTech Connect

This book discusses the papers presented at the conference on the subject of ''advances in Gene technology: Human genetic disorders''. Molecular biology of various carcinomas and inheritance of metabolic diseases is discussed and technology advancement in diagnosis of hereditary diseases is described. Some of the titles discussed are-Immunoglobulin genes translocation and diagnosis; hemophilia; oncogenes; oncogenic transformations; experimental data on mice, hamsters, birds carcinomas and sarcomas.

Scott, W.A.; Ahmad, F.; Black, S.; Schultz, J.; Whelan, W.J.



Approach to the diagnosis of congenital myopathies.  


Over the past decade there have been major advances in defining the genetic basis of the majority of congenital myopathy subtypes. However the relationship between each congenital myopathy, defined on histological grounds, and the genetic cause is complex. Many of the congenital myopathies are due to mutations in more than one gene, and mutations in the same gene can cause different muscle pathologies. The International Standard of Care Committee for Congenital Myopathies performed a literature review and consulted a group of experts in the field to develop a summary of (1) the key features common to all forms of congenital myopathy and (2) the specific features that help to discriminate between the different genetic subtypes. The consensus statement was refined by two rounds of on-line survey, and a three-day workshop. This consensus statement provides guidelines to the physician assessing the infant or child with hypotonia and weakness. We summarise the clinical features that are most suggestive of a congenital myopathy, the major differential diagnoses and the features on clinical examination, investigations, muscle pathology and muscle imaging that are suggestive of a specific genetic diagnosis to assist in prioritisation of genetic testing of known genes. As next generation sequencing becomes increasingly used as a diagnostic tool in clinical practise, these guidelines will assist in determining which sequence variations are likely to be pathogenic. PMID:24456932

North, Kathryn N; Wang, Ching H; Clarke, Nigel; Jungbluth, Heinz; Vainzof, Mariz; Dowling, James J; Amburgey, Kimberly; Quijano-Roy, Susana; Beggs, Alan H; Sewry, Caroline; Laing, Nigel G; Bönnemann, Carsten G



New Genetic Insights into Congenital Heart Disease  

PubMed Central

There has been remarkable progress in understanding the genetic basis of cardiovascular malformations. Chromosome microarray analysis has provided a new tool to understand the genetic basis of syndromic cardiovascular malformations resulting from microdeletion or microduplication of genetic material, allowing the delineation of new syndromes. Improvements in sequencing technology have led to increasingly comprehensive testing for aortopathy, cardiomyopathy, single gene syndromic disorders, and Mendelian-inherited congenital heart disease. Understanding the genetic etiology for these disorders has improved their clinical recognition and management and led to new guidelines for treatment and family-based diagnosis and surveillance. These new discoveries have also expanded our understanding of the contribution of genetic variation, susceptibility alleles, and epigenetics to isolated congenital heart disease. This review summarizes the current understanding of the genetic basis of syndromic and non-syndromic congenital heart disease and highlights new diagnostic and management recommendations. PMID:22822471

Ware, Stephanie M.; Jefferies, John Lynn



Batten disease: features to facilitate early diagnosis  

PubMed Central

Aims To ascertain the clinical and electrophysiological features in patients with juvenile neuronal ceroid lipofuscinosis (jNCL/Batten disease) and to identify those features that facilitate early diagnosis. Methods Nine patients with jNCL were identified retrospectively and their case notes reviewed. All had undergone an extensive clinical examination, including electrophysiology. Blood and molecular genetic testing confirmed the diagnosis. Results Age at onset ranged from 4–8?years. At presentation, two of nine patients had normal fundi; only two of nine patients had a bull's eye maculopathy. The electroretinogram (ERG) findings in this series included undetectable rod specific ERGs, an electronegative maximal response, reduced and delayed cone flicker ERGs, reduction in the b:a ratio in the photopic single flash ERG, and an undetectable pattern ERG. Vacuolated lymphocytes on peripheral blood film testing were present in eight of nine patients. Five of eight patients were homozygous for the 1.02?kb deletion on the CLN3 gene on molecular genetic testing; two of eight patients were heterozygous for that deletion. Conclusion jNCL should be considered in children of 10?years and under presenting with visual loss and fundal changes ranging from normal through to pigmentary/atrophic changes or a bull's eye maculopathy. Electrophysiology may suggest jNCL. Although currently untreatable, early diagnosis is important to institute appropriate counselling and support. PMID:16754648

Collins, J; Holder, G E; Herbert, H; Adams, G G W



Irritable bowel syndrome: Diagnosis and pathogenesis  

PubMed Central

Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder that considerably reduces the quality of life. It further represents an economic burden on society due to the high consumption of healthcare resources and the non-productivity of IBS patients. The diagnosis of IBS is based on symptom assessment and the Rome III criteria. A combination of the Rome III criteria, a physical examination, blood tests, gastroscopy and colonoscopy with biopsies is believed to be necessary for diagnosis. Duodenal chromogranin A cell density is a promising biomarker for the diagnosis of IBS. The pathogenesis of IBS seems to be multifactorial, with the following factors playing a central role in the pathogenesis of IBS: heritability and genetics, dietary/intestinal microbiota, low-grade inflammation, and disturbances in the neuroendocrine system (NES) of the gut. One hypothesis proposes that the cause of IBS is an altered NES, which would cause abnormal GI motility, secretions and sensation. All of these abnormalities are characteristic of IBS. Alterations in the NES could be the result of one or more of the following: genetic factors, dietary intake, intestinal flora, or low-grade inflammation. Post-infectious IBS (PI-IBS) and inflammatory bowel disease-associated IBS (IBD-IBS) represent a considerable subset of IBS cases. Patients with PI- and IBD-IBS exhibit low-grade mucosal inflammation, as well as abnormalities in the NES of the gut. PMID:23066308

El-Salhy, Magdy



A Diagnostic Technique for Multilevel Inverters Based on a Genetic-Algorithm to Select  

E-print Network

A Diagnostic Technique for Multilevel Inverters Based on a Genetic-Algorithm to Select a Principal principal component neural network method for fault diagnosis system in a multilevel inverter is proposed%. Index Terms -- Fault diagnosis, genetic algorithm, multilevel inverter, neural network, principal

Tolbert, Leon M.


A Place for Genetic Uncertainty: Parents Valuing an Unknown in the Meaning of Disease  

PubMed Central

Klinefelter, Turner, and fragile X syndromes are conditions defined by a genetic or chromosomal variant. The timing of diagnosis, tests employed, specialists involved, symptoms evident, and prognoses available vary considerably within and across these syndromes, but all three share in common a diagnosis verified through a molecular or cytogenetic test. The genetic or chromosomal variant identified designates a syndrome, even when symptoms associated with the particular syndrome are absent. This article analyzes interviews conducted with parents and grandparents of children with these syndromes from across the US to explore how they interpret a confirmed genetic diagnosis that is associated with a range of possible symptoms that may never be exhibited. Parents’ responses indicate that they see the genetic aspects of the syndrome as stable, permanent and authoritative. But they allow, and even embrace, uncertainty about the condition by focusing on variation between diagnosed siblings, the individuality of their diagnosed child, his or her accomplishments, and other positive aspects that go beyond the genetic diagnosis. Some families counter the genetic diagnosis by arguing that in the absence of symptoms, the syndrome does not exist. They use their own expertise to question the perceived certainty of the genetic diagnosis and to employ the diagnosis strategically. These multiple and often conflicting evaluations of the diagnostic label reveal the rich ways families make meaning of the authority attributed to genetic diagnosis. PMID:17561324

Whitmarsh, Ian; Davis, Arlene M.; Skinner, Debra; Bailey, Donald B



Eugenic selection benefits embryos.  


The primary question to be addressed here is whether pre-implantation genetic diagnosis (PGD), used for both negative and positive trait selection, benefits potential supernumerary embryos. The phrase 'potential supernumerary embryos' is used to indicate that PGD is typically performed on a set of embryos, only some of which will be implanted. Prior to any testing, each embryo in the set is potentially supernumerary in the sense that it may not be selected for implantation. Those embryos that are not selected, and hence destroyed or frozen, are 'actually supernumerary'. The argument to be advanced is hypothetical: If embryos may be said to benefit or be harmed by our actions, then PGD used to select for an embryo or embryos with the highest expected Wellbeing benefits potential supernumerary embryos. The argument shows that the 'non-identity' problem is not sufficient to show that eugenic selection does not benefit supernumerary embryos. PMID:22845885

Walker, Mark



Differential diagnosis of Charcot-Marie-Tooth disease and related neuropathies  

Microsoft Academic Search

The diagnosis of Charcot-Marie-Tooth disease (CMT) and related neuropathies (e. g. Déjèrine-Sottas disease; hereditary neuropathy with liability to pressure palsies) appears to be easy. However, the incredible advances in molecular genetics have greatly complicated the classification of these disorders, and the proper diagnosis of the CMT subtype may be important for correct genetic counselling and prognosis. Moreover, these diseases may

D. Pareyson



Molecular Diagnosis of Putative Stargardt Disease by Capture Next Generation Sequencing  

PubMed Central

Stargardt Disease (STGD) is the commonest genetic form of juvenile or early adult onset macular degeneration, which is a genetically heterogeneous disease. Molecular diagnosis of STGD remains a challenge in a significant proportion of cases. To address this, seven patients from five putative STGD families were recruited. We performed capture next generation sequencing (CNGS) of the probands and searched for potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes. Seven disease-causing mutations in ABCA4 and two in PROM1 were identified by CNGS, which provides a confident genetic diagnosis in these five families. We also provided a genetic basis to explain the differences among putative STGD due to various mutations in different genes. Meanwhile, we show for the first time that compound heterozygous mutations in PROM1 gene could cause cone-rod dystrophy. Our findings support the enormous potential of CNGS in putative STGD molecular diagnosis. PMID:24763286

Shi, Wei; Huang, Ping; Min, Qingjie; Li, Minghan; Yu, Xinping; Wu, Yaming; Zhao, Guangyu; Tong, Yi; Jin, Zi-Bing; Qu, Jia; Gu, Feng



Shingles: Diagnosis, Treatment, and Outcome  


... Diseases and treatments Q - T Shingles Diagnosis, treatment Shingles: Diagnosis, treatment, and outcome How do dermatologists diagnose shingles? To diagnose shingles, a dermatologist will look at ...


Melasma: Diagnosis, Treatment, and Outcome  


... Diseases and treatments M - P Melasma Diagnosis, treatment Melasma: Diagnosis, treatment, and outcome How do dermatologists diagnose melasma? Dermatologists can diagnose most patients by looking at ...


Salmonella Diagnosis and Treatment  


... About . Salmonella Share Compartir Diagnosis and Treatment How Can Salmonella Infections Be Diagnosed? Many different ... Typhi (Typhoid Fever) Associated with Frozen Mamey Fruit Pulp Case Count Map Epi Curve Hartford and Baildon ...


Medical Genetics and Genetics Is Medical Genetics or Genetics right for me?  

E-print Network

Medical Genetics and Genetics Is Medical Genetics or Genetics right for me? If you are interested Genetics or Genetics are subjects you should strongly consider. You will be expected to have a strong Genetics or Genetics are wide-ranging and provide a good basis for employment in varied sectors. Are all

Harman, Neal.A.


Diagnosis of urticaria  

PubMed Central

Acute urticaria do not need extensive diagnostic procedures. Urticaria activity score is a useful tool for evaluation of urticaria. Complete blood count, Erythrocyte sedimentation rate and C reactive protein are important investigations for diagnosis of infections in urticaria. Autologous serum skin test is a simple office procedure for diagnosis of auto reactive urticaria. Closed ball point pen tip is a simple test to diagnose dermographism. PMID:23723473

Schoepke, Nicole; Doumoulakis, Georgios; Maurer, Marcus



Clinical Features, Diagnosis, Pathology  

Microsoft Academic Search

\\u000a This chapter will review the clinical and histopathologic features associated with the presentation and diagnosis of retinoblastoma.\\u000a A thorough appreciation of the differential and a detailed clinical assessments is the cornerstone of arriving at the proper\\u000a diagnosis. Unlike most cancers, retinoblastoma is unique, as tissue is generally not necessary for diagnostic and treatment\\u000a purposes. However, once the eye is enucleated,

P. Chévez-Barrios; D. S. Gombos


Progress in molecular diagnosis of Charcot-Marie-Tooth-disease type 1 (CMT 1, HMSN I) and hereditary neuropathy with liability to pressure palsies (HNPP) by fluorescence in situ hybridization (FISH)-detection of a potential genetic mosaicism  

SciTech Connect

We tested 20 CMT 1 patients characterized according to the criteria of the European CMT consortium by Southern hybridization of MspI restricted genomic DNA with probes pVAW409R1, pVAW412Hec and pEW401HE. In 11 of the 20 CMT 1 cases (55%), we observed a duplication in 17q11.2; one patient had a dinucleotide insertion in exon 6 of the PO-gene (5%). One HNPP case had a typical 17p11.2 deletion. Analysis of CA-repeats was performed with primers RM11GT and Mfd41; SSCP-analysis of the PO, PMP22 and Cx32-genes is in progress. FISH was carried out with probe pVAW409R1. 125 interphase nuclei were analyzed for each proband by counting the signals per nucleus. Normal cells show a characteristic distribution of signals: 1 signal in 5.9% of nuclei, 2 in 86.3% and 3 in 7.8%. A duplication is indicated by a shift to 3 signals in more than approximately 60% and 2 in less than 25% of the nuclei. In contrast, the 17p11.2 deletion of the HNPP patient shifts to 82.4% of nuclei with a single hybridization signal versus 14.4% with 2 signals. We detected one case with significantly abnormal distribution of interphase nuclei hybridization signals compared to cultures of normal cells and to those with 17p11.2 duplication or deletion: 3.2% nuclei revealed 1 signal, 48.0% two signals and 48.8% 3 signals, indicating a pathogenic but moderate dosis increase compared to the throughout duplicated cases. FISH with probe pVAW409R1 is a versatile tool to detect the HNPP deletion both in interphase nuclei and in metaphase chromosomes. In CMT 1 disease interphase nuclei are required for FISH analysis due to the small duplication of 1.5 Mbp. In contrast to Southern techniques, FISH is able to detect genetic mosaicism.

Bathke, K.; Liehr. T.; Ekici, A. [Institute for Human Genetics, Erlange (Germany)] [and others



Microfluidic digital PCR enables rapid prenatal diagnosis of fetal aneuploidy  

E-print Network

of fetal chromo- somal abnormalities is the most com- mon indication for invasive prenatal testing.2GENETICS Microfluidic digital PCR enables rapid prenatal diagnosis of fetal aneuploidy H. Christina to have normal ploidy for the chromosomes tested. CONCLUSION: Microfluidic digital PCR allows detection

Quake, Stephen R.


Significance of Immunologic Markers in the Diagnosis of Lymphoma  

Microsoft Academic Search

The malignant lymphomas with indolent course present numerous diagnostic controversies, the frequent involvement of viral etiopathogeny, which can be followed up serologically, making these lymphomas an ideal topic for further study. The phenotypical and genetic heterogenity of the lymphomas make it difficult to elucidate the molecular mechanisms which concur in initiation and growth of these neoplasms. Therefore, the classification, diagnosis

M. Sathiya; K. Muthuchelian


Genetic Counseling Training  


Genetic Counseling Training Find out the answers the questions you may have about becoming a genetic counselor with these Frequently Asked ... Graduate School Simulated Genetic Counseling Sessions Genetic Counseling Training Programs Applying Interviewing Acceptance Learn More about Genetic ...


Biology 4250 Evolutionary Genetics  

E-print Network

Evolutionary Genetics Estimating genetic relationships: - clone mates from non-clone mates - genetic parentage among species - phylogenetic connections among more distantly related taxa Sexual reproduction + genetic: - realized reproductive success - genetic mating system vs. social mating systems (ie. monogamous) Empirical

Innes, David J.


New Insights on Taxonomy, Phylogeny and Population Genetics of Leishmania (Viannia) Parasites Based on Multilocus Sequence Analysis  

PubMed Central

The Leishmania genus comprises up to 35 species, some with status still under discussion. The multilocus sequence typing (MLST)—extensively used for bacteria—has been proposed for pathogenic trypanosomatids. For Leishmania, however, a detailed analysis and revision on the taxonomy is still required. We have partially sequenced four housekeeping genes—glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), mannose phosphate isomerase (MPI) and isocitrate dehydrogenase (ICD)—from 96 Leishmania (Viannia) strains and assessed their discriminatory typing capacity. The fragments had different degrees of diversity, and are thus suitable to be used in combination for intra- and inter-specific inferences. Species-specific single nucleotide polymorphisms were detected, but not for all species; ambiguous sites indicating heterozygosis were observed, as well as the putative homozygous donor. A large number of haplotypes were detected for each marker; for 6PGD a possible ancestral allele for L. (Viannia) was found. Maximum parsimony-based haplotype networks were built. Strains of different species, as identified by multilocus enzyme electrophoresis (MLEE), formed separated clusters in each network, with exceptions. NeighborNet of concatenated sequences confirmed species-specific clusters, suggesting recombination occurring in L. braziliensis and L. guyanensis. Phylogenetic analysis indicates L. lainsoni and L. naiffi as the most divergent species and does not support L. shawi as a distinct species, placing it in the L. guyanensis cluster. BURST analysis resulted in six clonal complexes (CC), corresponding to distinct species. The L. braziliensis strains evaluated correspond to one widely geographically distributed CC and another restricted to one endemic area. This study demonstrates the value of systematic multilocus sequence analysis (MLSA) for determining intra- and inter-species relationships and presents an approach to validate the species status of some entities. Furthermore, it contributes to the phylogeny of L. (Viannia) and might be helpful for epidemiological and population genetics analysis based on haplotype/diplotype determinations and inferences. PMID:23133690

Boite, Mariana C.; Mauricio, Isabel L.; Miles, Michael A.; Cupolillo, Elisa



Pervasive Diagnosis: Integration of Active Diagnosis into Production Plans  

E-print Network

Pervasive Diagnosis: Integration of Active Diagnosis into Production Plans Lukas Kuhn, Bob Price goals. The same model can be used by model-based diagnosis to indirectly infer the condition of components in a sys- tem from partially informative sensors. Existing work has demonstrated that diagnosis

de Kleer, Johan


Genetic testing.  


There have been rapid advances in genetics in recent years. DNA tests available on the Medicare Benefits Schedule (MBS) include HFE (haemochromatosis), Fragile X syndrome and Factor V Leiden. PMID:25006599

Pollack, Allan; Miller, Graeme



Genetics (image)  


... chromosome. The inheritance of genetic diseases, abnormalities, or traits is described by both the type of chromosome the abnormal gene resides on (autosomal or sex chromosome), and by whether the gene itself is dominant or recessive.


Genetic Alliance  


... Health Genes In Life Advocacy Publications Events Contact Main menu About Us - Council - Staff - Jobs and Internships - Press Releases - Annual Reports - Archives & History -- Introduction -- Genetic Alliance Archives -- Celebrating Our ...


Arthropod Genetics.  

ERIC Educational Resources Information Center

Introduces an activity on arthropod genetics that involves phenotype and genotype identification of the creature and the construction process. Includes a list of required materials and directions to build a model arthropod. (YDS)

Zumwalde, Sharon



Mutational Screening and Prenatal Diagnosis in Cornelia de Lange syndrome.  


Phenotypic variability and the lack of a diagnostic marker have complicated the rapid diagnosis and genetic counseling for Cornelia de Lange syndrome (CdLS). The clinical features of CdLS are striking and easily recognizable by characteristic facial dysmorphism, upper-extremity malformations, hirsutism, cardiac defects, growth and cognitive retardation, and gastrointestinal abnormalities with severe mental retardation. The molecular diagnosis is essential for predicting prognosis and genetic counseling in the affected family, especially while planning the next pregnancy. We report here from India six cases of CdLS and how precise mutational screening in two cases helped in prenatal diagnosis and proved significant in prevention of recurrence in the affected family. PMID:24587603

Dave, Usha; Shetty, Dhanlaxmi



Image processing for medical diagnosis using CNN  

NASA Astrophysics Data System (ADS)

Medical diagnosis is one of the most important area in which image processing procedures are usefully applied. Image processing is an important phase in order to improve the accuracy both for diagnosis procedure and for surgical operation. One of these fields is tumor/cancer detection by using Microarray analysis. The research studies in the Cancer Genetics Branch are mainly involved in a range of experiments including the identification of inherited mutations predisposing family members to malignant melanoma, prostate and breast cancer. In bio-medical field the real-time processing is very important, but often image processing is a quite time-consuming phase. Therefore techniques able to speed up the elaboration play an important rule. From this point of view, in this work a novel approach to image processing has been developed. The new idea is to use the Cellular Neural Networks to investigate on diagnostic images, like: Magnetic Resonance Imaging, Computed Tomography, and fluorescent cDNA microarray images.

Arena, Paolo; Basile, Adriano; Bucolo, Maide; Fortuna, Luigi



Diagnosis and management of primary ciliary dyskinesia.  


Primary ciliary dyskinesia (PCD) is an inherited autosomal-recessive disorder of motile cilia characterised by chronic lung disease, rhinosinusitis, hearing impairment and subfertility. Nasal symptoms and respiratory distress usually start soon after birth, and by adulthood bronchiectasis is invariable. Organ laterality defects, usually situs inversus, occur in ?50% of cases. The estimated prevalence of PCD is up to ?1 per 10,000 births, but it is more common in populations where consanguinity is common. This review examines who to refer for diagnostic testing. It describes the limitations surrounding diagnosis using currently available techniques and considers whether recent advances to genotype patients with PCD will lead to genetic testing and screening to aid diagnosis in the near future. It discusses the challenges of monitoring and treating respiratory and ENT disease in children with PCD. PMID:24771309

Lucas, Jane S; Burgess, Andrea; Mitchison, Hannah M; Moya, Eduardo; Williamson, Michael; Hogg, Claire



Diagnosis and management of primary ciliary dyskinesia  

PubMed Central

Primary ciliary dyskinesia (PCD) is an inherited autosomal-recessive disorder of motile cilia characterised by chronic lung disease, rhinosinusitis, hearing impairment and subfertility. Nasal symptoms and respiratory distress usually start soon after birth, and by adulthood bronchiectasis is invariable. Organ laterality defects, usually situs inversus, occur in ?50% of cases. The estimated prevalence of PCD is up to ?1 per 10?000 births, but it is more common in populations where consanguinity is common. This review examines who to refer for diagnostic testing. It describes the limitations surrounding diagnosis using currently available techniques and considers whether recent advances to genotype patients with PCD will lead to genetic testing and screening to aid diagnosis in the near future. It discusses the challenges of monitoring and treating respiratory and ENT disease in children with PCD. PMID:24771309

Lucas, Jane S; Burgess, Andrea; Mitchison, Hannah M; Moya, Eduardo; Williamson, Michael; Hogg, Claire



Guidelines for diagnosis and management of Beta-thalassemia intermedia.  


Beta-thalassemia intermedia (?-TI) is a genetic variant of beta-thalassemias with a clinical disorder whose severity falls between thalassemia minor and thalassemia major. Different genetic defects are involved in this disorder and, based on severity of disease, clinical complications like skeletal deformities and growth retardation, splenomegaly, extramedullary hematopoiesis, heart failure, and endocrine disorders may be present in untreated patients. Precise diagnosis and management are essential in these patients for prevention of later clinical complications. Diagnosis of TI is based on clinical and laboratory data. There are some treatment strategies like modulation of gamma-globulin chain production with hydroxyurea or other drugs, transfusion, splenectomy, and stem cell transplantation. Iron chelation therapy is also needed in many of these patients even if they are not transfused. The aim of this manuscript is to review the clinical manifestations, complications, genetic defects, and unmet treatments needs in TI. PMID:25247665

Karimi, Mehran; Cohan, Nader; De Sanctis, Vincenzo; Mallat, Naji S; Taher, Ali



Genetics Home Reference: CHMP2B-related frontotemporal dementia  


... OMIM Genetic disorder catalog Conditions > CHMP2B-related frontotemporal dementia On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed August 2010 What is CHMP2B-related frontotemporal dementia? CHMP2B -related frontotemporal dementia is a progressive brain ...


Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood  

E-print Network

of new noninvasive prenatal genetic tests for a variety of traits (11, 12). However, measuring aneuploidy, Stanford University, 300 Pasteur Drive, Room HH333, Stanford, CA 94305; and Division of Medical Genetics-generation sequencing noninvasive prenatal diagnosis Down syndrome trisomy Fetal aneuploidy and other chromosomal

Quake, Stephen R.


Genetics Home Reference: Genetic Conditions  


... the U.S. National Library of Medicine® Home Conditions Genes Chromosomes Handbook Glossary Resources Conditions Find a specific ... Act Copyright Privacy Accessibility Indicates a page outside Genetics Home Reference. Links to web sites outside the ...


Utility of RAPD markers in identifying genetic linkages to genes of economic interest in peach.  


The identification of molecular markers linked to economically important traits for use in crop improvement is very important in long-lived perennial species. Three-hundred-and-sixty RAPD primers were used with bulked segregant analysis to identify markers linked to loci of specific interest in peach [(Prunus persica) L. Batch] and peach x almond [(Prunus dulcis) Batch] crosses. The traits analyzed included flesh color, adhesion, and texture; pollen fertility; plant stature; and three isozyme loci. The Mendelian behavior of the RAPD loci was established, and RAPD markers were mapped relative to the loci controlling flesh color, adhesion, and texture, and the isozyme loci Mdh-1, 6Pgd-2 and Aat-1, as well as the existing RFLP genetic linkage map constructed previously using a peach x almond F2 population. This technique has facilitated rapid identification of RAPD and RFLP markers that are linked to the traits under study. Loci controlling these traits mapped predominantly to linkage groups 2 and 3 of the peach genetic linkage map. Linkages to genes with both dominant and co-dominant alleles were identified, but linkages to dominant genes were more difficult to find. In several crosses, RAPD marker bands proved to be allelic. One co-dominant RAPD formed a heteroduplex band in heterozygous individuals and in mixtures of alternate homozygotes. The Mendelian behavior of the RAPD loci studied was established and the results suggest that RAPD markers will be useful for plant improvement in peach. PMID:24162426

Warburton, M L; Becerra-Velásquez, V L; Goffreda, J C; Bliss, F A



International Symposium Genetic And Cellular Mechanisms  

E-print Network

International Symposium KFO 250 Genetic And Cellular Mechanisms In Autoimmune Diseases MHH Sitemap Diagnosis and therapy of autoimmune diseases require substantial medical experience with a risk of severe side effects. Comprehension of the etiology of systemic autoimmune diseases is rather

Manstein, Dietmar J.


Genetic Factors in Athetoid Cerebral Palsy  

Microsoft Academic Search

Within the cerebral palsy syndromes, athetosis is most commonly causally associated with serious perinatal complications. Genetic factors are thought to play a lesser role, although the risk of recurrence in siblings has been suggested to be as high as 10%. We have conducted a clinical study of 22 subjects with a diagnosis of athetoid cerebral palsy and a review of

David J. Amor; Jan E. Craig; Martin B. Delatycki; Dinah Reddihough



Remote diagnosis server  

NASA Technical Reports Server (NTRS)

A network-based diagnosis server for monitoring and diagnosing a system, the server being remote from the system it is observing, comprises a sensor for generating signals indicative of a characteristic of a component of the system, a network-interfaced sensor agent coupled to the sensor for receiving signals therefrom, a broker module coupled to the network for sending signals to and receiving signals from the sensor agent, a handler application connected to the broker module for transmitting signals to and receiving signals therefrom, a reasoner application in communication with the handler application for processing, and responding to signals received from the handler application, wherein the sensor agent, broker module, handler application, and reasoner applications operate simultaneously relative to each other, such that the present invention diagnosis server performs continuous monitoring and diagnosing of said components of the system in real time. The diagnosis server is readily adaptable to various different systems.

Deb, Somnath (Inventor); Ghoshal, Sudipto (Inventor); Malepati, Venkata N. (Inventor); Kleinman, David L. (Inventor); Cavanaugh, Kevin F. (Inventor)



[Diagnosis of human toxocarosis].  


Human toxocarosis is an important parasitic zoonosis caused by larval stages of Toxocara species, the roundworms from dogs and cats. Larval migration through different soft tissues in the human generates several clinical entities in the patient, such as visceral larva migrans, ocular toxocarosis, and neurotoxocarosis. Definitive diagnosis by histopathological methods is very difficult or almost impossible and, nowadays, the diagnosis is usually made by clinical signs/symptoms, epidemiological background of the patient and the use of hematological and immunological tests which finally help to confirm the clinical suspicion of the illness. The purpose of this paper was to update the available knowledge on the use of different tools for both the diagnosis and following up of human toxocarosis. PMID:21308204

Roldán, William H; Espinoza, Yrma A; Huapaya, Pedro E; Jiménez, Susana



Case for diagnosis*  

PubMed Central

Human scabies is an intensely pruritic skin infestation caused by Sarcoptes scabiei var. hominis. Crusted scabies (previously known as Norwegian scabies) is a rare form, very contagious and transmitted by direct contact with the skin. Despite being readily treatable, a delayed diagnosis often leads to widespread infestation of contacts, and therefore difficult to restrain. This case concerns a patient where dermoscopy (with scabetic burrows and a visible hand-glider structure), together with direct microscopic examination, allowed a prompt diagnosis, thereby reinforcing the increasing importance of this technique in daily practice. PMID:24173196

Cabral, Rita; Coutinho, Inês; Reis, José Pedro



Basal cell carcinoma - diagnosis  

PubMed Central

Basal cell carcinoma is the most common skin cancer in the Caucasian population. The cancer arises in sun exposed areas of the skin. The incidence of morbidity is high and it is still growing. The metastatic rate is low, but the enlarging tumor may cause severe tissue disfigurement and a poor cosmetic outcome. The diagnosis is usually clinical but there are many subtypes of this carcinoma and correct diagnosis is the clue to appropriate treatment of the lesion. The main problem in basal cell carcinoma management is the high recurrence rate. PMID:24592119

Bowszyc-Dmochowska, Monika; Strzelecka-Weklar, Daria; Danczak-Pazdrowska, Aleksandra; Adamski, Zygmunt



Vulvodynia. Definition, diagnosis and treatment.  


Vulvodynia is a chronic painful disorder with an estimated prevalence of 9-12%. A rising incidence of the condition constitutes a growing problem. This has lead to an increased focus on etiology and treatment, while the definition also requires attention. Previous assumptions stating that the problem is solely a psychological disorder have been abandoned, because inflammatory mechanisms and genetic factors have been found to be involved in the pathogenesis as well as psychosexual contributors. This article describes the terminology and definition of the condition, theories on patho-physiological mechanisms underlying the disorder, methods of diagnosis and evidence and recommendations on clinical management. A critical examination of the literature regarding vulvodynia reveals numerous strategies and recommendations for treatment, many of which are not evidence-based, and a lack of effective treatment for all patients. Research is being undertaken internationally to find more specific and unequivocal causes of the disorder, as well as to develop evidence-based methods of treatment. PMID:18720031

Petersen, Christina Damsted; Lundvall, Lene; Kristensen, Ellids; Giraldi, Annamaria



Pulmonary Hypertension: Diagnosis and Management  

PubMed Central

Pulmonary arterial hypertension is a progressive, symptomatic, and ultimately fatal disorder for which substantial advances in treatment have been made during the past decade. Effective management requires timely recognition and accurate diagnosis of the disorder and appropriate selection among therapeutic alternatives. Despite progress in treatment, obstacles remain that impede the achievement of optimal outcomes. The current article provides an overview of the pathobiologic mechanisms of pulmonary arterial hypertension, including genetic substrates and molecular and cellular mechanisms, and describes the clinical manifestations and classification of pulmonary arterial hypertension. The article also reviews established approaches to evaluation and treatment, with emphasis on the appropriate application of calcium channel blockers, prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors. In addition, the authors discuss unresolved issues that may complicate patient management, such as the clinical importance of mild or exercise-related pulmonary arterial hypertension, and they identify avenues by which treatment may advance in the future through the use of combination treatment, outcomes assessment, and exploration of alternative pharmacologic strategies. PMID:19181654

McGoon, Michael D.; Kane, Garvan C.




PubMed Central

Thyroid cancer exists in several forms. Differentiated thyroid cancers include papillary and follicular histologies. These tumors exist along a spectrum of differentiation, and their incidence continues to climb. A number of advances in the diagnosis and treatment of differentiated thyroid cancers now exist. These include molecular diagnostics and more advanced strategies for risk stratification. Medullary cancer arises from the parafollicular cells and not the follicular cells. Therefore, diagnosis and treatment differs from differentiated thyroid tumors. Genetic testing and newer adjuvant therapies has changed the diagnosis and treatment of medullary thyroid cancer. This review will focus on the epidemiology, diagnosis, work-up, and treatment of both differentiated and medullary thyroid cancers, focusing specifically on newer developments in the field. PMID:23797834

Schneider, David F.; Chen, Herbert



[Diagnosis, differential diagnosis and therapy of lymphedema].  


Swellings in the legs, caused by lymphedema, are encountered quite frequently in everyday orthopedic practice. The swellings are hard, pale in color and usually painful. Swellings of this kind occasionally atrain a completely disproportionate size and are the referred to as elephantiasis. Lymphedemas fall into two categories: 1. Congenital lymphedemas. These comprise lymphedemas occuring as a result of aplasias or dysplasias of lymph vessels. 2. Acquired lymphedemas: In such cases the edema may be due to mechanical causes, or it may be the result of a disturbance of lymph drainage, e.g., due to the destruction of lymph vessels by metastases, following extirpation of lymph nodes and radiation therapy; or it may be the result of inflammatory processes, e.g., following erysipelas, in filariasis or after a wound infection. Four stages of lymphedema are also distinguished: Stage I - latent lymphedema Stage II - reversible lymphedema Stage III - irreversible lymphedema Stage IV - Elephantiasis. Apart from clinical diagnosis the most comprehensive and reliable diagnostic procedure is lymphangiography. A simple and well-tried method of diagnosing lymphedema is to inject lymphotropic dye subcutaneously. The technique is outlined. The differential diagnosis of lymphedema is described. With regard to treatment, reference is made to surgical possibilities. However, these do not always augur success and the complication rate is high. Massive lymphedemas, therefore, are usually treated conservatively, by Van der Molen's tube method, with intermittent cuff pressure (pressure-curve therapy) and manual lymph drainage. The various treatment methods are described and some of the disadvantage and risks involved are pointed out. PMID:7080630

Dustmann, H O



Lymphangioleiomyomatosis: differential diagnosis and optimal management  

PubMed Central

Lymphangioleiomyomatosis (LAM) is an uncommon disease presented as diffuse thin-walled cystic changes in the lung. The main differential diagnoses include pulmonary Langerhans’ histiocytosis (PLCH), Birt-Hogg-Dubé syndrome (BHD), lymphoid interstitial pneumonia (LIP), and amyloidosis. A combination of clinical, radiological, and pathological approaches as well as genetic testing will clarify the diagnosis in most cases. LAM is a disease almost exclusively in women. Dyspnea, pneumothorax, and hemoptysis are common presentations in LAM patients. LAM is also a lymphatic disorder affecting lymphatic vessels and lymph nodes. Chylothorax, chylous ascites, and lymphangiomyomas are frequently seen. LAM can present sporadically as a single entity or as part of tuberous sclerosis complex (TSC). Angiomyolipoma (AML) is a characteristic extra-pulmonary lesion, either found in association with sporadic or TSC-related LAM. High-risk populations should be screened for LAM, including adult women with TSC and female patients with spontaneous pneumothorax, AMLs in the kidney, and diffuse cystic lung diseases. Definitive diagnosis of LAM is based on a high level of clinical suspicion on presentation supported by pathological findings or by a distinct feature, such as a history of TSC, AMLs in the kidney, chylothorax, or chylous ascites. Vascular endothelial growth factor-D (VEGF-D) in serum is a noninvasive and reliable diagnostic biomarker. In experienced centers, trans-bronchial lung biopsy (TBLB) provides a convenient and safe way to obtain lung specimens for diagnostic purposes. An effective treatment for LAM is now available, namely using a mechanistic target of rapamycin (mTOR) inhibitor such as sirolimus. Efficacy of sirolimus has been confirmed in clinical trials. Research in other molecular-targeted therapies is under investigation. A previously little-known rare disease with no cure is now better understood with regards to its pathogenesis, diagnosis, and management. In this review, current knowledge in diagnosis and differential diagnosis of LAM will be discussed, followed by the discussion of therapy with mTOR inhibitors. PMID:25187723

Xu, Kai-Feng; Lo, Bee Hong



Genetic Engineering  

NSDL National Science Digital Library

The Discovery Education website serves as a repository of instructional materials for educators seeking to help their charges learn about everything from the solar system to genetically modified organisms. This particular lesson plan deals with the science and technology of genetic engineering and it is intended to be used by advanced high school and community college students. Users will appreciate the fact that the entire plan is well-organized and divided into 12 sections including Objectives, Discussion Questions, and Procedures. The Discussion Questions are thoughtful and well-articulated and one can imagine that each query might generate more than a bit of meditation and close consideration.

Morrissette-Johnson, Winona


Discrimination as a consequence of genetic testing.  

PubMed Central

Genetic discrimination refers to discrimination directed against an individual or family based solely on an apparent or perceived genetic variation from the "normal" human genotype. We describe here the results of a case history study designed to assess whether or not genetic discrimination exists. Using the above definition of genetic discrimination and applying stringent criteria for case selection, we find that genetic discrimination exists and is manifested in many social institutions, especially in the health and life insurance industries. Stigmatization, and denial of services or entitlements to individuals who have a genetic diagnosis but who are asymptomatic or who will never become significantly impaired, is noted. Follow-up comprehensive studies on the significance and varieties of genetic discrimination are needed. In order to avoid creating a new social underclass based on genetic discrimination (the "asymptomatic ill"), existing and future genetic testing or screening programs need review by medical, scientific, legal, and social policy experts, as well as the public, and may require modification. PMID:1539589

Billings, P R; Kohn, M A; de Cuevas, M; Beckwith, J; Alper, J S; Natowicz, M R



Genetic determinants of plasma triglycerides  

PubMed Central

Plasma triglyceride (TG) concentration is reemerging as an important cardiovascular disease risk factor. More complete understanding of the genes and variants that modulate plasma TG should enable development of markers for risk prediction, diagnosis, prognosis, and response to therapies and might help specify new directions for therapeutic interventions. Recent genome-wide association studies (GWAS) have identified both known and novel loci associated with plasma TG concentration. However, genetic variation at these loci explains only ?10% of overall TG variation within the population. As the GWAS approach may be reaching its limit for discovering genetic determinants of TG, alternative genetic strategies, such as rare variant sequencing studies and evaluation of animal models, may provide complementary information to flesh out knowledge of clinically and biologically important pathways in TG metabolism. Herein, we review genes recently implicated in TG metabolism and describe how some of these genes likely modulate plasma TG concentration. We also discuss lessons regarding plasma TG metabolism learned from various genomic and genetic experimental approaches. Treatment of patients with moderate to severe hypertriglyceridemia with existing therapies is often challenging; thus, gene products and pathways found in recent genetic research studies provide hope for development of more effective clinical strategies. PMID:21041806

Johansen, Christopher T.; Kathiresan, Sekar; Hegele, Robert A.



Genetic Susceptibility to Pancreatic Cancer  

PubMed Central

Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States. However, it has the poorest prognosis of any major tumor type, with a 5-yr survival rate of approximately 5%. Cigarette smoking, increased body mass index, heavy alcohol consumption, and a diagnosis of diabetes mellitus have all been demonstrated to increase risk of pancreatic cancer. A family history of pancreatic cancer has also been associated with increased risk suggesting inherited genetic factors also play an important role, with approximately 5–10% of pancreatic cancer patients reporting family history of pancreatic cancer. While the genetic basis for the majority of the familial clustering of pancreatic cancer remains unclear, several important pancreatic cancer genes have been identified. These consist of high penetrance genes including BRCA2 or PALB2, to more common genetic variation associated with a modest increase risk of pancreatic cancer such as genetic variation at the ABO blood group locus. Recent advances in genotyping and genetic sequencing have accelerated the rate at which novel pancreatic cancer susceptibility genes have been identified with several genes identified within the past few years. This review addresses our current understanding of the familial aggregation of pancreatic cancer, established pancreatic cancer susceptablity genes and how this knowledge informs risk assessment and screening for high-risk families. PMID:22162228

Klein, Alison P.



Assessment, Diagnosis, and Treatment.  

ERIC Educational Resources Information Center

The purpose of this paper is to provide an overview of assessment, diagnosis, and treatment planning for individuals with substance abuse problems. The intent is to provide information to professional counselors in school, rehabilitation, school psychology, social work, public mental health, and private treatment settings. Information to be…

Mullis, Thomas


[Urticaria: diagnosis and treatment].  


Urticaria is a common inflammatory skin disease. It is clinically defined as the occurrence of transient papular skin and/or mucosal lesions or subcutaneous lesions called angioedema. Chronic urticaria is defined as a clinical course over more than 6weeks. Different clinical forms of urticaria can coexist in the same patient. Urticaria results of mast cell activation. The diagnosis of urticaria is based on clinical examination. An allergic etiology for acute urticaria, although rare, is always to find and remove. Chronic urticaria is not allergic. Diagnosis is based on questioning and a careful clinical examination to rule out differential diagnoses. Few diagnostic tests are necessary for diagnosis and management, and are especially useful in case of doubtful diagnosis. The treatment of urticaria is symptomatic and based on anti-H1 second generation antihistamines as first-line therapy. In some chronic urticarial, antihistamines up dosing may be necessary. In the majority of patients, this treatment is sufficient to control chronic urticaria. In case of antihistamines failure, other treatment particularly immunomodulatory treatments can be offered in specialized departments. PMID:24581819

Soria, A; Francès, C



What Makes Diagnosis Hard?  

ERIC Educational Resources Information Center

This essay uses a case study to explore some of the reasons why understanding failures associated with diagnosis seems to have lagged behind the attention and understanding directed at failures in other aspects of healthcare (e.g., wrong patient/procedure, medication misadministration, etc). The goal is not to pose an alternative to many of the…

Wears, Robert L.



Prenatal diagnosis: whose right?  

PubMed Central

The question who is the subject of the right to prenatal diagnosis may be answered in four ways: the parents, the child, society, or no one. This article investigates the philosophical issues involved in each of these answers, which touch upon the conditions of personal identity, the principle of privacy, the scope of social responsibility, and the debate about impersonalism in ethics. PMID:8558544

Heyd, D



Multi-Disciplinary Diagnosis.  

ERIC Educational Resources Information Center

The diagnosis of severely retarded pupils as an interdisciplinary concern is discussed. Descriptions of the severe reading disability syndrome given by various disciplines are presented under the following headings: Neurological Factors--minimal brain damage, lateral dominance; Physical Factors--endocrine and metabolic disorders, optical and…

Schiffman, Gilbert B.


Cutaneous sarcoidosis: differential diagnosis  

Microsoft Academic Search

Sarcoidosis is a multisystem disease with cutaneous lesions present in 20%-35% of patients. Given the wide variability of clinical manifestations, it is one of the “great imitators,” making it necessary to consider clinical, epidemiological, radiographic, laboratory, and histopathological criteria to make the diagnosis.Cutaneous lesions have been classified as specific and nonspecific, depending on the presence of noncaseating granulomas on histologic

Esteban Fernandez-Faith; Jonelle McDonnell



An overview of the role of genotyping in the diagnosis of the primary hyperoxalurias.  


The aim of this paper is to give an overview of our current state of knowledge with respect to genotyping for the primary hyperoxalurias and the role of molecular genetics alongside the more traditional biochemical and enzymatic tests for the diagnosis and prognosis of these disorders. The published literature was reviewed to establish the frequency of different mutations and thus the value of testing for a limited number of these mutations in patients with clinical suspicion of primary hyperoxaluria (PH). This approach was compared with whole gene sequencing of the AGXT and GRHPR genes. A limited genetic screen can provide a first line test for PH1 and PH2 in symptomatic patients and can provide a full diagnosis in approximately a third of cases. Molecular genetic analysis is essential for carrier testing and prenatal diagnosis. The value of molecular genetics in prognosis requires a wider evidence base. PMID:16208537

Rumsby, Gill



Reasons for Adult Referrals for Genetic Counseling at a Genetics Center in Izmir, Turkey: Analysis of 8965 Cases over an Eleven-Year Period  

Microsoft Academic Search

A limited numbers of published studies evaluate the referral reasons for genetic counseling services in the literature. These\\u000a studies are focused on prenatal genetic counseling services, in particular, prenatal diagnosis. In order to provide the most\\u000a effective and helpful genetic counseling services, genetics professionals need adequate knowledge about the profile of individuals\\u000a referred for these services. In addition, physicians need

Ozgur Cogulu; Ferda Ozkinay; Haluk Akin; Huseyin Onay; Emin Karaca; Asude Alpman Durmaz; Burak Durmaz; Ayca Aykut; Erhan Pariltay; Ozgur Kirbiyik; Cumhur Gunduz; Cihangir Ozkinay



Huntington's disease: pathogenesis, diagnosis and treatment.  

PubMed Central

This review of the clinical features of Huntington's disease incorporates recent developments in pathophysiology, preclinical diagnosis and treatment. Although the mechanism initiating and guiding the cell destruction in this illness is currently unknown, the excitatory neurotoxin and the energy metabolism models may provide a valuable direction for future research. Similarly, although the precise relation between the neuroanatomical damage in Huntington's disease and the functional disability is not clear, applications of recently developed neural connection models have implicated a number of important brain-behavior associations. Preclinical diagnostic procedures have evolved through successive iterations that have each contributed to increased reliability. New functional brain imaging techniques are sure to add to this promising domain in the future. Preclinical diagnosis has been stimulated by the recent isolation of the Huntington's gene which has also rekindled awareness of the importance of informed genetic counselling and the inherent ethical dilemmas in genetic testing. Treatment approaches to Huntington's disease have been confined to palliative care with secondary symptom management and psychotherapeutic support. Experimental therapeutic strategies for the illness itself have had a rather disappointing record to date. Further developments in NMDA antagonism and neural cell grafting may provide some hope for the future. PMID:7528535

Purdon, S E; Mohr, E; Ilivitsky, V; Jones, B D



Genetic Testing  


... In some cases, there is no treatment. But test results might help a person make life decisions, such as family planning or insurance coverage. A genetic counselor can provide information about the pros and cons of testing. NIH: National Human Genome Research Institute


Genetic Drift  

NSDL National Science Digital Library

In this biology simulation, students use a mathematical simulation of genetic drift to answer questions about the factors that influence this evolutionary process. Students run a series of simulations varying allele frequency and population size and then analyze their data and propose a model to explain their results.

Cooper, Scott


Genetics and \\  

Microsoft Academic Search

This essay argues that the influence of medical pseudo-science in a number of passages in The Merchant of Venice is much stronger than Shakespeare scholars generally acknowledge. Early modern notions of genetics in the play have a bearing on its conceptualization of \\

Martin Japtok; Winfried Schleiner



Understanding Genetics  

NSDL National Science Digital Library

While most people may retain a smattering of information and basic concepts about the field of genetics, some may also wish to refresh their knowledge base, and the Understanding Genetics website is a fine way to get back up to speed. Created and maintained by the good people at the Tech Museum of Innovation in San Jose, the homepage is well thought out, and provides a nice entry point to many of the features available here. Visitors can peruse the questions posed to geneticists in the "Ask a Geneticist" feature, browse a selection of recent news stories regarding genetics, and take a survey on the ethical questions posed by the issues of stem cell research and genetically modified foods. The feature story is a fine resource as well, as it provides basic, non-jargon-laden answers to such question as "What is a gene?" and "How do genes work?". The site also contains a number of activities that can be done at home, including a fun exercise that teaches users how to extract DNA from strawberries.


Genetic Determinants of Urolithiasis  

PubMed Central

Urolithiasis affects approximately 10% of individuals in Western societies by the seventh decade of life. The most common form, idiopathic calcium oxalate urolithiasis, results from the interaction of multiple genes and their interplay with dietary and environmental factors. To date, considerable progress has been made identifying the metabolic risk factors predisposing to this complex trait, among which hypercalciuria predominates. The specific genetic and epigenetic factors have remained less clear, in part due to the candidate gene and linkage methods available until now, which are inherently low in their power of resolution and in assessing modest effects in complex traits. Even so, this approach, together with investigations of rare, Mendelian forms of urolithiasis associated with various metabolic risk factors has afforded insights into biological pathways that appear to underlie the development of stones in the urinary tract. Monogenic diseases account for a greater proportion of stone formers in childhood and adolescence than in adults. Early diagnosis of monogenic forms of urolithiasis is of importance due to associated renal injury and other potentially treatable disease manifestations, but is often delayed due to lack of familiarity with these rare disorders. Genetic advances in polygenic and monogenic forms of urolithiasis are reviewed. PMID:22183508

Monico, Carla G.; Milliner, Dawn S.



Genetics of SCID  

PubMed Central

Human SCID (Severe Combined Immunodeficiency) is a prenatal disorder of T lymphocyte development, that depends on the expression of numerous genes. The knowledge of the genetic basis of SCID is essential for diagnosis (e.g., clinical phenotype, lymphocyte profile) and treatment (e.g., use and type of pre-hematopoietic stem cell transplant conditioning). Over the last years novel genetic defects causing SCID have been discovered, and the molecular and immunological mechanisms of SCID have been better characterized. Distinct forms of SCID show both common and peculiar (e.g., absence or presence of nonimmunological features) aspects, and they are currently classified into six groups according to prevalent pathophysiological mechanisms: impaired cytokine-mediated signaling; pre-T cell receptor defects; increased lymphocyte apoptosis; defects in thymus embryogenesis; impaired calcium flux; other mechanisms. This review is the updated, extended and largely modified translation of the article "Cossu F: Le basi genetiche delle SCID", originally published in Italian language in the journal "Prospettive in Pediatria" 2009, 156:228-238. PMID:21078154



Genetics Home Reference: Acatalasemia  


... and researchers. Genetic Testing Registry - Repository of genetic test information (2 links) PubMed - Recent literature OMIM - Genetic disorder catalog What other names do people use for acatalasemia? acatalasia catalase deficiency For more information about naming genetic conditions, ...


Genetics Home Reference: Aniridia  


... Reviews - Clinical summary Genetic Testing Registry - Repository of genetic test information (1 link) - Linking patients to medical ... Diseases Information Center . Where can I find general information about genetic conditions? The Handbook provides basic information about genetics ...


Genetic Counseling Program Information  

E-print Network

Genetic Counseling Program Information for Potential Applicants #12;Wayne State Genetic Counseling Program Overview "Genetic counseling is the process of helping people understand and adapt to the medical, psychological, and familial implications of genetic contributions to disease. The process integrates

Berdichevsky, Victor


Early diagnosis of spondyloarthritis  

Microsoft Academic Search

The term 'spondyloarthritis', which is preferred to 'spondyloarthropathy', refers to a group of similar diseases with distinct clinical features and a common genetic predisposition, rather than one disease with different clinical presentations. Mainly for clinical purposes, five disease subtypes are recognized: ankylosing spondylitis (AS), psoriatic spondyloarthritis, reactive spondyloarthritis, spondyloarthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthritis. Irrespective of the

Jürgen Braun; Joachim Sieper



[Diagnosis and treatment of multiple endocrine neoplasia type 2A: a case report and literature review].  


We report a case of multiple endocrine neoplasia (MEN) type 2A and summarize the clinical characteristics, diagnosis and treatment of this condition. The diagnosis of MEN type 2A relies on a comprehensive evaluation of the findings of ultrasound, CT and laboratory examinations, and early diagnosis and treatment is critical to improving the prognosis. Genetic testing of RET is the gold standard for diagnosis of MEN type 2A and 2B. Surgical intervention currently remains the primary choice of treatments of this disease. PMID:24968855

Yu, Ruofei; Wu, Ziqing; Li, Aimin; Jin, Guoping; Luo, Rongcheng



Inclusion-Body Myositis: Diagnosis  


... MDA Search form Search Inclusion-Body Myositis (IBM) Diagnosis As with other muscle diseases, a doctor diagnoses ... biopsy can enable the physician to pinpoint the diagnosis to a type of myositis. The biopsy sample ...


Aicardi syndrome: Neonatal diagnosis by means of transfontanellar ultrasound.  


Aicardi syndrome is a rare genetic disease characterized by a characteristic classical trio of neurological clinical abnormalities (spasms), agenesis of the corpus callosum and ophthalmological abnormalities (chorioretinal lacunae). The diagnosis can be suspected by prenatal ultrasound with color Doppler identifying the agenesis of the corpus callosum. Usually, the diagnosis is confirmed in the neonate period by transfontanellar ultrasound and ophthalmological examination. We present a case of newborn with Aicardi syndrome, being the transfontanellar identified partial dysgenesis of the corpus callosum and a cyst in the inter-hemispheric fissure. Ophthalmological examination showed bilateral chorioretinal lacunae. PMID:25071893

Pires, Claudio Rodrigues; Araujo Júnior, E; Czapkowski, Adriano; Zanforlin Filho, Sebastião Marques



Genetic Testing in Presymptomatic Diagnosis of Multiple Endocrine Neoplasia  

Microsoft Academic Search

Multiple endocrine neoplasias (MEN) are familial diseases characterized by endocrine neoplasms and transmitted in an autosomal dominant manner. In MEN type I, the major lesions affect parathyroid glands, pancreatic islet cells and anterior pituitary. The MEN-1 gene has been mapped to chomosome 11q13 and a set of DNA-polymorphic markers localized close to this region provides a useful tool for presymptomatic

A. Calender; S. Giraud; I. Schuffenecker; G. M. Lenoir; P. Gaudray; A. Courseaux; N. Porchet; J. P. Aubert; C. X. Zhang



Molecular genetics and diagnosis of phenylketonuria: state of the art.  


Detection of individuals with phenylketonuria (PKU), an autosomal recessively inherited disorder in phenylalanine degradation, is straightforward and efficient due to newborn screening programs. A recent introduction of the pharmacological treatment option emerged rapid development of molecular testing. However, variants responsible for PKU do not all suppress enzyme activity to the same extent. A spectrum of over 850 variants, gives rise to a continuum of hyperphenylalaninemia from very mild, requiring no intervention, to severe classical PKU, requiring urgent intervention. Locus-specific and genotypes database are today an invaluable resource of information for more efficient classification and management of patients. The high-tech molecular methods allow patients' genotype to be obtained in a few days, especially if each laboratory develops a panel for the most frequent variants in the corresponding population. PMID:24882081

Blau, Nenad; Shen, Nan; Carducci, Carla



Molecular Karyotyping: Array CGH Quality Criteria for Constitutional Genetic Diagnosis  

Microsoft Academic Search

Array CGH (comparative genomic hybridization) enables the identification of chromosomal copy number changes. The availability of clone sets covering the human genome opens the possibility for the widespread use of array CGH for both research and diagnostic purposes. In this manuscript we report on the parameters that were critical for successful implementation of the technology, assess quality criteria, and discuss

Joris R. Vermeesch; Cindy Melotte; Guy Froyen; Steven Van Vooren; Binita Dutta; Nicole Maas; Stefan Vermeulen; Björn Menten; Frank Speleman; Bart De Moor; Paul Van Hummelen; Peter Marynen; Jean-Pierre Fryns; Koen Devriendt



Diagnosis of scrub typhus.  


Scrub typhus is an acute febrile illness that, if untreated, can result in considerable morbidity and mortality. One of the primary reasons for delays in the treatment of this potentially fatal infection is the difficulty in diagnosing the condition. Diagnosis is often complicated because of the combination of non-specific symptoms that overlap with other infections commonly found in endemic areas and the poor available diagnostics. In the majority of the endemic settings, diagnosis still relies on the Weil-Felix test, which is neither sensitive nor specific. Other methods of testing have become available, but at this time, these remain insufficient to provide the rapid point-of-care diagnostics that would be necessary to significantly change the management of this infection by providers in endemic areas. This article reviews the currently available diagnostic tools for scrub typhus and their utility in the clinical setting. PMID:25359599

Janardhanan, Jeshina; Trowbridge, Paul; Varghese, George M



Hemobilia: computed tomographic diagnosis  

SciTech Connect

A case of postbiopsy hemobilia is presented in which computed tomographic (CT) scanning showed blood within the gallbladder appearing as high-density material measuring 67-91 HU. Residual clots were seen by CT and ultrasound 8 days after the acute episode. These findings were confirmed by serial CT scans in two monkeys in whom blood was experimentally injected into the gallbladder. When the cystic duct is patent, the diagnosis of hemobilia may be excluded if bile of normal density (0-20 HU) is demonstrated by CT scanning. However, when homogeneous or inhomogeneous material of high attenuation (50+ HU) is present in the gallbladder on CT scanning, the diagnosis of hemobilia is strongly suggested if other causes such as stone or contrast material have been eliminated. CT may show residual blood for days after the acute episode.

Krudy, A.G.; Doppman, J.L.; Bissonette, M.B.; Girton, M.



Cutaneous sarcoidosis: differential diagnosis.  


Sarcoidosis is a multisystem disease with cutaneous lesions present in 20%-35% of patients. Given the wide variability of clinical manifestations, it is one of the "great imitators," making it necessary to consider clinical, epidemiological, radiographic, laboratory, and histopathological criteria to make the diagnosis. Cutaneous lesions have been classified as specific and nonspecific, depending on the presence of noncaseating granulomas on histologic studies. Specific lesions include maculopapules, plaques, nodules, lupus pernio, scar infiltration, alopecia, ulcerative lesions, and hypopigmentation among others. Nail, mucosal, and childhood sarcoidosis represent a distinct subset of the disease process. The most common nonspecific lesion is erythema nodosum. Others include calcifications, prurigo, erythema multiforme, nail clubbing, and Sweet syndrome. The importance of considering cutaneous sarcoidosis in the clinical differential diagnosis of a given skin lesion relies on the association with systemic involvement and the convenience of the skin as a tissue source for histologic analysis. PMID:17560305

Fernandez-Faith, Esteban; McDonnell, Jonelle



Diagnosis of Prostate Cancer  

Microsoft Academic Search

The contemporary challenge of prostate cancer diagnosis has been changed in the past decade from the endeavor to increase\\u000a detection to that of detecting only those tumors that are clinically significant. Better interpretation of the role of prostate-specific\\u000a antigen (PSA) and its kinetics as a diagnostic tool, the adoption of extended prostate biopsy schemes, and perhaps implementation\\u000a of new transrectal

Jehonathan H. Pinthus; Dalibor Pacik; Jacob Ramon


Deformation Zone Diagnosis  

NSDL National Science Digital Library

Following an analysis of the main features of a deformation zone, the diagnosis of temporal and spatial changes in these features can be used to deduce underlying meteorological processes and their progression. In turn, this knowledge can then be used in the forecast process to adjust the forecast accordingly. This module takes 35-45 minutes to complete. It is part of the series: "Dynamic Feature Identification: The Satellite Palette".




Karyotypes to Predict Genetic Disorders- A Lesson on Genetics  

NSDL National Science Digital Library

This teaching resource was developed by a K-12 science teacher in the American Physiological SocietyÃÂs 2008 Frontiers in Physiology Program. For more information on this program, please visit The purpose of this activity is to explain how a human karyotype is used to identify specific genetic disorders. During this lab students will research new treatments, the inheritance, diagnosis, and their application to biology, and symptoms or complications of a specific genetic disorder. Also, students will hypothesize what will happen to the frequencies of two alleles as a result of the presence of malaria in a population. Students should already have prior knowledge of the use of a pedigree and the similarities and differences of sex chromosomes and autosomes. Upon completion of this activity, students will be able to: identify chromosome pairs based upon band patterns and location of centromere and observe how selective forces can change allele frequencies in a population and cause evolution to occur.

Karen Walton (Chapin High School)



Culture and psychiatric diagnosis.  


Since the publication of DSM-IV in 1994, neurobiologists and anthropologists have criticized the rigidity of its diagnostic criteria that appear to exclude whole classes of alternate illness presentations, as well as the lack of attention in contemporary psychiatric nosology to the role of contextual factors in the emergence and characteristics of psychopathology. Experts in culture and mental health have responded to these criticisms by revising the very process of diagnosis for DSM-5. Specifically, the DSM-5 Cultural Issues Subgroup has recommended that concepts of culture be included more prominently in several areas: an introductory chapter on Cultural Aspects of Psychiatric Diagnosis - composed of a conceptual introduction, a revised Outline for Cultural Formulation, a Cultural Formulation Interview that operationalizes this Outline, and a glossary on cultural concepts of distress - as well as material directly related to culture that is incorporated into the description of each disorder. This chapter surveys these recommendations to demonstrate how culture and context interact with psychiatric diagnosis at multiple levels. A greater appreciation of the interplay between culture, context, and biology can help clinicians improve diagnostic and treatment planning. PMID:23816860

Lewis-Fernández, Roberto; Aggarwal, Neil Krishan



Publications Fish Disease Diagnosis and  

E-print Network

Publications Fish Disease Diagnosis and Basic Fishery Computer Programs The second edition of "Disease Diagnosis and Control in North American Marine Aquaculture," edited by Carl J. Sindermann on correct diagnosis, proper preventive measures, and proper treatment, and this vastly updated second


The Diagnosis of Mitochondrial Diseases  

E-print Network

The Diagnosis of Mitochondrial Diseases #12;Front cover: Mitochondrial morphology in human of Dr. Estela Area-Gomez. The Diagnosis of Mitochondrial Diseases at Columbia University Medical Center consultation and diagnosis Full range of enzyme diagnostics Analysis of mitochondrial DNA Research

Qian, Ning


Cerebellar hypoplasia: differential diagnosis and diagnostic approach.  


Cerebellar hypoplasia (CH) refers to a cerebellum with a reduced volume, and is a common, but non-specific neuroimaging finding. The etiological spectrum of CH is wide and includes both primary (malformative) and secondary (disruptive) conditions. Primary conditions include chromosomal aberrations (e.g., trisomy 13 and 18), metabolic disorders (e.g., molybdenum cofactor deficiency, Smith-Lemli-Opitz syndrome, and adenylosuccinase deficiency), genetic syndromes (e.g., Ritscher-Schinzel, Joubert, and CHARGE syndromes), and brain malformations (primary posterior fossa malformations e.g., Dandy-Walker malformation, pontine tegmental cap dysplasia and rhombencephalosynapsis, or global brain malformations such as tubulinopathies and ?-dystroglycanopathies). Secondary (disruptive) conditions include prenatal infections (e.g., cytomegalovirus), exposure to teratogens, and extreme prematurity. The distinction between malformations and disruptions is important for pathogenesis and genetic counseling. Neuroimaging provides key information to categorize CH based on the pattern of involvement: unilateral CH, CH with mainly vermis involvement, global CH with involvement of both vermis and hemispheres, and pontocerebellar hypoplasia. The category of CH, associated neuroimaging findings and clinical features may suggest a specific disorder or help plan further investigations and interpret their results. Over the past decade, advances in neuroimaging and genetic testing have greatly improved clinical diagnosis, diagnostic testing, recurrence risk counseling, and information about prognosis for patients and their families. In the next decade, these advances will be translated into deeper understanding of these disorders and more specific treatments. PMID:24839100

Poretti, Andrea; Boltshauser, Eugen; Doherty, Dan



Modern Genetics  

NSDL National Science Digital Library

This initial module from the GENIQUEST project introduces the dragons and the inheritance of their traits, then delves into meiosis and its relationship to inherited traits. Students examine the effects of choosing different gametes on dragon offspring, and learn about genetic recombination by creating recombination events to generate specific offspring from two given parent dragons. Students learn about inbred strains and breed an inbred strain of dragons themselves.

Consortium, The C.



Mitochondrial genetics  

PubMed Central

Introduction In the last 10 years the field of mitochondrial genetics has widened, shifting the focus from rare sporadic, metabolic disease to the effects of mitochondrial DNA (mtDNA) variation in a growing spectrum of human disease. The aim of this review is to guide the reader through some key concepts regarding mitochondria before introducing both classic and emerging mitochondrial disorders. Sources of data In this article, a review of the current mitochondrial genetics literature was conducted using PubMed ( In addition, this review makes use of a growing number of publically available databases including MITOMAP, a human mitochondrial genome database (, the Human DNA polymerase Gamma Mutation Database ( and (, a repository of global mtDNA variation. Areas of agreement The disruption in cellular energy, resulting from defects in mtDNA or defects in the nuclear-encoded genes responsible for mitochondrial maintenance, manifests in a growing number of human diseases. Areas of controversy The exact mechanisms which govern the inheritance of mtDNA are hotly debated. Growing points Although still in the early stages, the development of in vitro genetic manipulation could see an end to the inheritance of the most severe mtDNA disease. PMID:23704099

Chinnery, Patrick Francis; Hudson, Gavin



Update 2011: Clinical and Genetic Issues in Familial Dilated Cardiomyopathy  

PubMed Central

A great deal of progress has recently been made in the discovery and understanding of the genetics of familial dilated cardiomyopathy (FDC). A consensus has emerged that with a new diagnosis of idiopathic dilated cardiomyopathy (IDC), the clinical screening of 1st degree family members will reveal FDC in at least 20-35% of cases. Point mutations in 31 autosomal and 2 X-linked genes representing diverse gene ontogeny have been implicated in causing FDC, but account for only 30-35% of genetic cause. Next generation sequencing (NGS) methods have dramatically decreased sequencing costs, making clinical genetic testing feasible for extensive panels of DCM genes. NGS also provides opportunities to discover additional genetic cause of FDC and IDC. Guidelines for evaluation and testing of FDC and IDC are now available, and when combined with FDC genetic testing and counseling will bring FDC/IDC genetics to the forefront of cardiovascular genetic medicine. PMID:21492761

Hershberger, Ray E.; Siegfried, Jill D.



Genetic causes of spermatogenic failure  

PubMed Central

Approximately 10%–15% of couples are infertile, and a male factor is involved in almost half of these cases. This observation is due in part to defects in spermatogenesis, and the underlying causes, including genetic abnormalities, remain largely unknown. Until recently, the only genetic tests used in the diagnosis of male infertility were aimed at detecting the presence of microdeletions of the long arm of the Y chromosome and/or chromosomal abnormalities. Various other single-gene or polygenic defects have been proposed to be involved in male fertility. However, their causative effects often remain unproven. The recent evolution in the development of whole-genome-based techniques and the large-scale analysis of mouse models might help in this process. Through knockout mouse models, at least 388 genes have been shown to be associated with spermatogenesis in mice. However, problems often arise when translating this information from mice to humans. PMID:22138898

Massart, Annelien; Lissens, Willy; Tournaye, Herman; Stouffs, Katrien



Judaism, Genetic Screening and Genetic Therapy  

Microsoft Academic Search

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



Parkinson's Disease: From Genetics to Clinical Practice  

PubMed Central

Breakthroughs in genetics over the last decade have radically advanced our understanding of the etiological basis of Parkinson's disease (PD). Although much research remains to be done, the main genetic causes of this neurodegenerative disorder are now partially unraveled, allowing us to feel more confident that our knowledge about the genetic architecture of PD will continue to increase exponentially. How and when these discoveries will be introduced into general clinical practice, however, remains uncertain. In this review, we provide a general summary of the progress in the genetics of PD and discuss how this knowledge will contribute to the diagnosis and clinical management of patients with, or at risk of this disorder. PMID:24532987

Clarimon, Jordi; Kulisevsky, Jaime



Genetic analysis in bartter syndrome from India.  


Bartter syndrome is a group of inherited, salt-losing tubulopathies presenting as hypokalemic metabolic alkalosis with normotensive hyperreninemia and hyperaldosteronism. Around 150 cases have been reported in literature till now. Mutations leading to salt losing tubulopathies are not routinely tested in Indian population. The authors have done the genetic analysis for the first time in the Bartter syndrome on two cases from India. First case was antenatal Bartter syndrome presenting with massive polyuria and hyperkalemia. Mutational analysis revealed compound heterozygous mutations in KCNJ1(ROMK) gene [p(Leu220Phe), p(Thr191Pro)]. Second case had a phenotypic presentation of classical Bartter syndrome however, genetic analysis revealed only heterozygous novel mutation in SLC12A gene p(Ala232Thr). Bartter syndrome is a clinical diagnosis and genetic analysis is recommended for prognostication and genetic counseling. PMID:24696311

Sharma, Pradeep Kumar; Saikia, Bhaskar; Sharma, Rachna; Ankur, Kumar; Khilnani, Praveen; Aggarwal, Vinay Kumar; Cheong, Hae



Striving for Harmonisation and Living Without it  

Microsoft Academic Search

In the last decade human embryo research, i.e. stem cell research, therapeutic cloning, reproductive cloning and Preimplantation\\u000a Genetic Diagnosis (PGD), has become one of the most controversial bioethical issues scientists as well as ethicists, legal\\u000a experts, politicians and the public have been confronted with. Besides various national debates there have been a number of\\u000a attempts to harmonise these morally problematic

Minou Friele


Attitudes of Mothers towards Their Child with Down Syndrome before and after the Introduction of Prenatal Diagnosis  

ERIC Educational Resources Information Center

In 1970, before the introduction of prenatal diagnosis of chromosome anomalies, an unpublished questionnaire study concerning the social and emotional situation of mothers of children with Down syndrome was conducted in southern Germany. To assess the psychosocial impact of the availability of prenatal diagnosis on parents of genetically

Lenhard, Wolfgang; Breitenbach, Erwin; Ebert, Harald; Schindelhauer-Deutscher, H. Joachim; Zang, Klaus D.; Henn, Wolfram



Diagnosis of DVT  

PubMed Central

Background: Objective testing for DVT is crucial because clinical assessment alone is unreliable and the consequences of misdiagnosis are serious. This guideline focuses on the identification of optimal strategies for the diagnosis of DVT in ambulatory adults. Methods: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Results: We suggest that clinical assessment of pretest probability of DVT, rather than performing the same tests in all patients, should guide the diagnostic process for a first lower extremity DVT (Grade 2B). In patients with a low pretest probability of first lower extremity DVT, we recommend initial testing with D-dimer or ultrasound (US) of the proximal veins over no diagnostic testing (Grade 1B), venography (Grade 1B), or whole-leg US (Grade 2B). In patients with moderate pretest probability, we recommend initial testing with a highly sensitive D-dimer, proximal compression US, or whole-leg US rather than no testing (Grade 1B) or venography (Grade 1B). In patients with a high pretest probability, we recommend proximal compression or whole-leg US over no testing (Grade 1B) or venography (Grade 1B). Conclusions: Favored strategies for diagnosis of first DVT combine use of pretest probability assessment, D-dimer, and US. There is lower-quality evidence available to guide diagnosis of recurrent DVT, upper extremity DVT, and DVT during pregnancy. PMID:22315267

Jaeschke, Roman; Stevens, Scott M.; Goodacre, Steven; Wells, Philip S.; Stevenson, Matthew D.; Kearon, Clive; Schunemann, Holger J.; Crowther, Mark; Pauker, Stephen G.; Makdissi, Regina; Guyatt, Gordon H.



Toward molecular pathogenesis of an autoimmune disease: Refined genetic mapping of autoimmune polyglandular disease type I (APECED)  

SciTech Connect

Autoimmune reactions encoupled to many human diseases are still only partially understood. Unravelling the molecular pathogenesis of inherited diseases with a strong autoimmune component in their clinical expression could help to dissect individual components in the molecular background of abnormal immune response. One such genetic disorder is autosomal recessive autoimmune polyglandular disease type I (PGD I), also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, MIM 240300). The disease is especially enriched in the genetically isolated population of Finland and we have assigned the APECED locus to human chromosome 21q22.3 in 14 Finnish families by linkage analyses. The best positional lod score of 6.49 was observed with marker D21S49. Based on the history of the Finns, the gene pool of this population clearly demonstrates the consequences of a founder effect and consequent isolation. In the Finnish population, we can take advantage of linkage disequilibrium and allelic association studies to more precisely define the critical DNA region for our disease gene of interest than would be possible by linkage analyses alone. We are now able to define the chromosomal region of interest between two flanking markers locating 1 cM apart. Linkage disequilibrium is observed with three of the markers used in the analyses and this suggests a distance of less than 500 kb to the disease locus, well approachable with molecular cloning techniques. Overlapping YAC and cosmid clones spanning our region of interest will facilitate the cloning of APECED gene in the near future.

Aaltonen, J.; Bjoerses, P.; Peltonen, L. [National Public Health Institute, Helsinki (Finland)] [and others



Molecular diagnosis of putative Stargardt disease probands by exome sequencing  

PubMed Central

Background The commonest genetic form of juvenile or early adult onset macular degeneration is Stargardt Disease (STGD) caused by recessive mutations in the gene ABCA4. However, high phenotypic and allelic heterogeneity and a small but non-trivial amount of locus heterogeneity currently impede conclusive molecular diagnosis in a significant proportion of cases. Methods We performed whole exome sequencing (WES) of nine putative Stargardt Disease probands and searched for potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes. Follow-up dideoxy sequencing was performed for confirmation and to screen for mutations in an additional set of affected individuals lacking a definitive molecular diagnosis. Results Whole exome sequencing revealed seven likely disease-causing variants across four genes, providing a confident genetic diagnosis in six previously uncharacterized participants. We identified four previously missed mutations in ABCA4 across three individuals. Likely disease-causing mutations in RDS/PRPH2, ELOVL, and CRB1 were also identified. Conclusions Our findings highlight the enormous potential of whole exome sequencing in Stargardt Disease molecular diagnosis and research. WES adequately assayed all coding sequences and canonical splice sites of ABCA4 in this study. Additionally, WES enables the identification of disease-related alleles in other genes. This work highlights the importance of collecting parental genetic material for WES testing as the current knowledge of human genome variation limits the determination of causality between identified variants and disease. While larger sample sizes are required to establish the precision and accuracy of this type of testing, this study supports WES for inherited early onset macular degeneration disorders as an alternative to standard mutation screening techniques. PMID:22863181



Drug allergy diagnosis.  


Poorly documented and often self-reported drug hypersensitivity (DH) is a frequent problem in daily clinical practice and has a considerable impact on prescription choices. Little is known about the natural history of true DH. The suspicion of DH starts on clinical grounds. When assessing a patient with a presumed DH reaction in the symptomatic phase, it is mandatory to look for severity signs and, after doing so, to update the risk/benefit balance of exploring the suspected drug(s) on a case-by-case basis. With the help of allergy tests and a careful approach, a firm diagnosis is often possible. PMID:25017672

Chiriac, Anca M; Demoly, Pascal



Case for diagnosis.  


A 27-year-old mixed-raced (pardo) female patient presented with flat ovate hypochromic plaques with a rough surface on the back and upper limbs, with an aspect resembling pityriasis versicolor. She reports family history involving a brother with similar lesions. Lab tests, including anti-HIV, showed no alterations and a histopathological examination showed enlarged keratinocytes with basophilic and microvacuolated cytoplasm occupying the upper portion of the spinous layer and the granulous layer. After anatomic-clinical correlation, the diagnosis of epidermodysplasia verruciformis pityriasis versicolor like was confirmed. PMID:21603836

Ribas, Jonas; Corrêa, Clarisse de Albuquerque; Cavalcante, Melissa de Souza Melo



Case for diagnosis.  


The Osler-Weber-Rendu syndrome or Hereditary Hemorrhagic Telangiectasia (HHT) is a systemic fibrovascular dysplasia characterized by defects in the elastic and vascular walls of blood vessels, making them varicose and prone to disruptions. Lesions occur in different organs and can lead to hemorrhage in the lungs, digestive tract and brain. We describe the case of a patient with cutaneous manifestations and severe impairment of the digestive tract. It is important for the dermatologist to recognize this syndrome, since the cutaneous lesions may play a key role in diagnosis. PMID:25387512

Boza, Juliana Catucci; Dorn, Timotio Volnei; Oliveira, Fabiana Bazanella de; Bakos, Renato Marchiori



Diagnosis of leishmaniasis.  


Leishmaniasis is a clinically heterogeneous syndrome caused by intracellular protozoan parasites of the genus Leishmania. The clinical spectrum of leishmaniasis encompasses subclinical (not apparent), localized (skin lesion), and disseminated (cutaneous, mucocutaneous, and visceral) infection. This spectrum of manifestations depends on the immune status of the host, on the parasite, and on immunoinflammatory responses. Visceral leishmaniasis causes high morbidity and mortality in the developing world. Reliable laboratory methods become mandatory for accurate diagnosis, especially in immunocompromised patients such as those infected with HIV. In this article, we review the current state of the diagnostic tools for leishmaniasis, especially  the serological test. PMID:25116660

Elmahallawy, Ehab Kotb; Sampedro Martinez, Antonio; Rodriguez-Granger, Javier; Hoyos-Mallecot, Yannick; Agil, Ahamd; Navarro Mari, Jose Mari; Gutierrez Fernandez, Jose



Case for diagnosis*  

PubMed Central

The Osler-Weber-Rendu syndrome or Hereditary Hemorrhagic Telangiectasia (HHT) is a systemic fibrovascular dysplasia characterized by defects in the elastic and vascular walls of blood vessels, making them varicose and prone to disruptions. Lesions occur in different organs and can lead to hemorrhage in the lungs, digestive tract and brain. We describe the case of a patient with cutaneous manifestations and severe impairment of the digestive tract. It is important for the dermatologist to recognize this syndrome, since the cutaneous lesions may play a key role in diagnosis. PMID:25387512

Boza, Juliana Catucci; Dorn, Timotio Volnei; de Oliveira, Fabiana Bazanella; Bakos, Renato Marchiori



How genetics came to the unborn: 1960-2000.  


Prenatal diagnosis (PND) is frequently identified with genetic testing. The termination of pregnancy for foetal malformation was called 'genetic abortion', in spite of the fact that in many cases the malformation does not result from changes in the genetic material of the cell. This study argues that the 'geneticization' of PND reflected the transformation of the meaning of the term 'genetics' in the 1960s and 70s. Such transformation was linked with the definition of Down syndrome as a genetic condition, and to the key role of search for this condition in the transformation of PND into a routine approach. The identification of PND with the polysemic term 'genetics' was also favoured by hopes that cytogenetic studies will lead to cures or prevention of common birth defects, the association of genetic counsellors with prenatal diagnosis, and the raising prestige of clinical genetics. In spite of the impressive achievements of the latter specialty, more than fifty years after the first prenatal diagnoses, the main 'cure' of a severe foetal malformation remains the same as it was in the 1960s: the termination of a pregnancy. The identification of PND with genetics deflects attention from the gap between scientists' capacity to elucidate the causes of numerous birth defects and their ability (as for now) to prevent or treat these defects, and favours the maintenance of a powerful regimen of hope. PMID:24968964

Löwy, Ilana



Differential diagnosis of hyponatraemia.  


The appropriate management of hyponatraemia is reliant on the accurate identification of the underlying cause of the hyponatraemia. In the light of evidence which has shown that the use of a clinical algorithm appears to improve accuracy in the differential diagnosis of hyponatraemia, the European Hyponatraemia Network considered the use of two algorithms. One was developed from a nephrologist's view of hyponatraemia, while the other reflected the approach of an endocrinologist. Both of these algorithms concurred on the importance of assessing effective blood volume status and the measurement of urine sodium concentration in the diagnostic process. To demonstrate the importance of accurate diagnosis to the correct treatment of hyponatraemia, special consideration was given to hyponatraemia in neurosurgical patients. The differentiation between the syndrome of inappropriate antidiuretic hormone secretion (SIADH), acute adrenocorticotropic hormone (ACTH) deficiency, fluid overload and cerebral salt-wasting syndrome was discussed. In patients with SIADH, fluid restriction has been the mainstay of treatment despite the absence of an evidence base for its use. An approach to using fluid restriction to raise serum tonicity in patients with SIADH and to identify patients who are likely to be recalcitrant to fluid restriction was also suggested. PMID:22469249

Thompson, Chris; Berl, Tomas; Tejedor, Alberto; Johannsson, Gudmundur



Laboratory Diagnosis of Amebiasis  

PubMed Central

The detection of Entamoeba histolytica, the causative agent of amebiasis, is an important goal of the clinical microbiology laboratory. To assess the scope of E. histolytica infection, it is necessary to utilize accurate diagnostic tools. As more is discovered about the molecular and cell biology of E. histolytica, there is great potential for further understanding the pathogenesis of amebiasis. Molecular biology-based diagnosis may become the technique of choice in the future because establishment of these protozoa in culture is still not a routine clinical laboratory process. In all cases, combination of serologic tests with detection of the parasite (by antigen detection or PCR) offers the best approach to diagnosis, while PCR techniques remain impractical in many developing country settings. The detection of amebic markers in serum in patients with amebic colitis and liver abscess appears promising but is still only a research tool. On the other hand, stool antigen detection tests offer a practical, sensitive, and specific way for the clinical laboratory to detect intestinal E. histolytica. All the current tests suffer from the fact that the antigens detected are denatured by fixation of the stool specimen, limiting testing to fresh or frozen samples. PMID:14557296

Tanyuksel, Mehmet; Petri, William A.



Diagnosis of pseudomembranous colitis.  

PubMed Central

Twenty-eight patients with histologically proved pseudomembranous colitis have been seen in one hospital since July 1975. All patients with the disease had received antibiotics, six for infections not requiring operations; the other 22 cases all occurred after major surgery. All the patients had diarrhoea; six patients also had fever with clinical signs of sepsis, and three had abdominal pain thought to be due to anastomotic dehiscence after colonic resection. Pseudomembranous colitis was associated with white blood counts over 15 000/mm3 in 17 patients and albumin concentrations of less than 30 g/1 in 18. Pseudomembranous colitis was an incidental finding at necropsy in two of six patients who had not had an operation. Of the 22 patients who had had major surgery, nine died from this complication; in all except two of these cases the diagnosis was made only at necropsy. If pseudomembranous colitis is suspected on clinical grounds or if there is an unexplained complication after colorectal surgery repeat sigmoidoscopy and testing for faecal toxins should be carried out to establish the diagnosis so that prompt supportive treatment can be given. PMID:630292

Kappas, A; Shinagawa, N; Arabi, Y; Thompson, H; Burdon, D; Dimock, F; George, R H; Alexander-Williams, J; Keighley, M R



Outcomes of genetics services: creating an inclusive definition and outcomes menu for public health and clinical genetics services.  


Third party payers, funding agencies, and lawmakers often require clinicians and public health agencies to justify programs and services by documenting results. This article describes two assessment tools--"Defining Genetics Services Framework" and "Genetics Services Outcomes Menu," created to assist public health professionals, clinicians, family advocates, and researchers to plan, evaluate, and demonstrate the effectiveness of genetics services. The tools were developed by a work group of the Western States Genetics Services Collaborative (WSGSC) consisting of public health genetics and newborn screening professionals, family representatives, a medical geneticist, and genetic counselors from Alaska, California, Hawaii, Idaho, Oregon, and Washington. The work group created both tools by an iterative process of combining their ideas with findings from a literature and World Wide Web review. The Defining Genetics Services Framework reflects the diversity of work group members. Three over-lapping areas of genetics services from public health core functions to population screening to clinical genetics services are depicted. The Genetics Services Outcomes Menu lists sample long-term outcomes of genetics services. Menu outcomes are classified under impact areas of Knowledge and Information; Financing; Screening and Identification; Diagnosis, Treatment, and Management; and Population Health. The WSGSC incorporated aspects of both tools into their Regional Genetics Plan. PMID:19621453

Silvey, Kerry; Stock, Jacquie; Hasegawa, Lianne E; Au, Sylvia Mann



[Pheochromocytoma: update on diagnosis and therapy].  


Pheochromocytomas (P) are rare catecholamine producing neuroendocrine tumors originating from the chromaffin cells of the adrenal medulla or in 15?% of cases from extra adrenal chromaffin tissue and termed paragangliomas (PGL). Because of secretion of the catecholamines - adrenaline, noradrenaline and dopamine - the tumors are dangerous with a risk of life threating hypertensive crises. Measurements of plasma metanephrine, normetanephrine and methoxytyramine by liquid chromatography with tandem mass spectrometry provides the most accurate and precise method for biochemical diagnosis. Approximately 30-40?% of the tumors have a hereditary background due to mutations of 11 known susceptibility genes, with identification facilitated by targeted genetic testing according to clinical presentation. Apart from syndrome-dependent clinical stigmata, other hints to an underlying mutation can be provided by biochemical profiles of the catecholamine metabolites, tumor location, patient age and presence of metastatic disease. Surgery with minimal invasive procedures is the recommended therapeutic way after pretreatment with an alpha receptor blocking medication. PMID:24570195

Gruber, M; Därr, R; Eisenhofer, G



[Amyotrophic lateral sclerosis--diagnosis and treatment].  


Amyotrophic lateral sclerosis (ALS) represents the most common motoneuron disorder in adulthood. It is characterized by selective degeneration of the motoneurons. About 10% of patients have a genetically determined ALS. Clinically, ALS is characterized by coexistence of signs of the first motoneuron, such as spasticity and hyperreflexia, as well as the second motoneuron, such as muscular atrophy and fasciculations. If such signs are present in at least three regions and if other possible causes have been excluded, a definite diagnosis of ALS can be made based on the revised El-Escorial criteria. Initial manifestations are often focalized and generalization develops during the course. The glutamate antagonist riluzole is worldwide the only approved ALS treatment. However, symptomatic treatments to ameliorate spasticity, drooling, speech and swallowing problems, and assisted ventilation to treat respiratory failure are essential. PMID:22763933

Jung, H H; Neumann, M; Bloch, K E



Posttraumatic intrahepatic biloma: sonographic diagnosis  

SciTech Connect

Posttraumatic intrahepatic biliary cysts or bilomas were once thought to be rare. With increased use of sonography and /sup 99m/Tc-HIDA cholescintigraphy, this entity will probably be detected more often. Preoperative sonographic diagnosis of posttraumatic biloma was made in five patients. A well circumscribed, anechoic hepatic lesion with excellent distal sonic enhancement strongly suggests the diagnosis. Cholescintigraphy especially using delayed scans or percutaneous aspiration, can confirm the diagnosis.

Esensten, M.; Ralls, P.W.; Colletti, P.; Halls, J.



Syndromic obesity: clinical implications of a correct diagnosis  

PubMed Central

Background Although individual occurrence is rare, syndromic obesity with mental retardation has been reported in conjunction with 140 different diseases. Case presentation The patient was born at term after a pregnancy complicated by threatened miscarriage. A diagnosis of Bardet-Biedl syndrome (BBS; OMIM #209900) was made in another hospital when she was 8 years old, but other clinical problems emerged subsequently. She came to our attention for the first time when she was 14 years old. The clinical picture, characterized by the presence of ophtalmological, renal, endocrinological, and liver disorders associated with a peculiar weight growth pattern, was more suggestive for Alström syndrome (ALMS; OMIM #203800); consequently, a genetic study was performed. Genetic analysis revealed a novel compound heterozygous frameshift mutation on exon 8 of ALMS1 (c. [3251_3258delCTGACCAG] and c. [6731delA]), which has not previously been described. Conclusion Early onset of retinal degeneration associated with obesity represents a diagnostic challenge in paediatric and genetic practice, although the absence of skeletal abnormalities and developmental delay could help in addressing the clinical diagnosis. Confirmation of clinical suspicion by genetic analysis has been diriment in this case, since only a single gene is known to cause ALMS. PMID:24690487



Genetics and Neuromuscular Diseases  


Facts About Genetics and Neuromuscular Diseases Updated December 2009 2 Genetics and Neuromuscular Diseases • ©2011 MDA Dear Friends: M ost of ... appeared. What kind of sample is needed for genetic testing? Usually, only a blood sample is needed, ...


Genetics Home Reference: Cherubism  


... Research studies PubMed Recent literature OMIM Genetic disorder catalog Conditions > Cherubism On this page: Description Genetic ... however, this condition occurs as part of another genetic disorder. For example, cherubism can occur with Ramon syndrome, ...


Biology 4250 Evolutionary Genetics  

E-print Network

8. Sex and Evolution 9. Conservation Genetics 10. Human Evolutionary Genetics Estimating genetic substitutions Sexual Asexual #12;3 Protozoa, Bacteria, Fungi - agents of human disease - asexual strains polygynandry 3. Hermaphroditic: selfing outcrossing 4. Uniparental: Selfing vs. parthenogenesis Intensity

Innes, David J.


Photobacteriosis: Prevention and Diagnosis  

PubMed Central

Photobacteriosis or fish pasteurellosis is a bacterial disease affecting wild and farm fish. Its etiological agent, the gram negative bacterium Photobacterium damselae subsp. piscicida, is responsible for important economic losses in cultured fish worldwide, in particular in Mediterranean countries and Japan. Efforts have been focused on gaining a better understanding of the biology of the pathogenic microorganism and its natural hosts with the aim of developing effective vaccination strategies and diagnostic tools to control the disease. Conventional vaccinology has thus far yielded unsatisfactory results, and recombinant technology has been applied to identify new antigen candidates for the development of subunit vaccines. Furthermore, molecular methods represent an improvement over classical microbiological techniques for the identification of P. damselae subsp. piscicida and the diagnosis of the disease. The complete sequencing, annotation, and analysis of the pathogen genome will provide insights into the pathogen laying the groundwork for the development of vaccines and diagnostic methods. PMID:24982922



Hybrid Systems Diagnosis  

NASA Technical Reports Server (NTRS)

This paper reports on an on-going Project to investigate techniques to diagnose complex dynamical systems that are modeled as hybrid systems. In particular, we examine continuous systems with embedded supervisory controllers that experience abrupt, partial or full failure of component devices. We cast the diagnosis problem as a model selection problem. To reduce the space of potential models under consideration, we exploit techniques from qualitative reasoning to conjecture an initial set of qualitative candidate diagnoses, which induce a smaller set of models. We refine these diagnoses using parameter estimation and model fitting techniques. As a motivating case study, we have examined the problem of diagnosing NASA's Sprint AERCam, a small spherical robotic camera unit with 12 thrusters that enable both linear and rotational motion.

McIlraith, Sheila; Biswas, Gautam; Clancy, Dan; Gupta, Vineet



Case for diagnosis*  

PubMed Central

Intravascular papillary endothelial hyperplasia is a benign vascular lesion caused by proliferation of endothelium. It is reactive to thrombotic or inflammatory stimuli in the vessel wall.We report the case of a 14-yearold male patient with a violet-colored erythematous tumoral lesion of progressive growth in the occipital region. The diagnosis of intravascular papillary endothelial hyperplasia (IPEH) was confirmed by clinical and histopathological findings. Total lesion exeresis was performed with no recurrence up to date. IPEH presents clinical importance due to its clinical and histological resemblance to angiosarcoma. In order to differentiate it from angiosarcoma, distinguishing features of the benign disease should be considered, such as lack of cellular atypia and rare mitotic activity.Prognosis is good. PMID:25054765

Fabre, Andrea Buosi; Passos, Paola C. Vieira da Rosa; de Lima, Brunno Zeni; Fabricio, Lincoln; Fillus, Jose; Bonalumi, Aguinaldo



[Diagnosis of delayed puberty].  


Puberty is the phenomenon that conducts once to reproductive maturation. Delayed puberty (DP) is defined by the absence of testicular development in boys beyond 14 years old (or a testicular volume lower than 4 ml) and by the absence of breast development in girls beyond 13 years old. DP occurs in approximatively 3% of cases. Most cases are functional DP, with a large amount of constitutional delay of puberty. Others etiologies are hypogonadotrophic hypogonadism like Kallmann syndrome, or hypergonadotrophic hypogonadism. Turner syndrome is a diagnostic one should not forget by its frequency. Treatment is hormonal replacement therapy and of the etiology. During the last decade, many genes have been identified and elucidated the etiological diagnosis of some hypogonadotrophic hypogonadism syndrome. Further studies are required in collaboration with molecular biologists to better understand the mechanism of hypothalamic pituitary gonadal axis abnormalities and of the neuroendocrine physiology of the onset of puberty. PMID:17658248

Busiah, K; Belien, V; Dallot, N; Fila, M; Guilbert, J; Harroche, A; Leger, J



Importance of genetic evaluation and testing in pediatric cardiomyopathy  

PubMed Central

Pediatric cardiomyopathies are clinically heterogeneous heart muscle disorders that are responsible for significant morbidity and mortality. Phenotypes include hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, left ventricular noncompaction and arrhythmogenic right ventricular cardiomyopathy. There is substantial evidence for a genetic contribution to pediatric cardiomyopathy. To date, more than 100 genes have been implicated in cardiomyopathy, but comprehensive genetic diagnosis has been problematic because of the large number of genes, the private nature of mutations, and difficulties in interpreting novel rare variants. This review will focus on current knowledge on the genetic etiologies of pediatric cardiomyopathy and their diagnostic relevance in clinical settings. Recent developments in sequencing technologies are greatly impacting the pace of gene discovery and clinical diagnosis. Understanding the genetic basis for pediatric cardiomyopathy and establishing genotype-phenotype correlations may help delineate the molecular and cellular events necessary to identify potential novel therapeutic targets for heart muscle dysfunction in children.

Tariq, Muhammad; Ware, Stephanie M



Genetic contributions to pain: a review of findings in humans  

PubMed Central

Pain represents the major motivating factor for which individuals seek healthcare, and pain responses are characterized by substantial inter-individual differences. Increasing evidence suggests that genetic factors contribute significantly to individual differences in responses to both clinical and experimental pain. The purpose of this review article was to summarize the current literature regarding genetic contributions to pain, highlighting findings relevant to oral pain where available. A brief discussion of methodologic considerations is followed by a review of findings regarding genetic influences on clinical pain. Next, the literature examining genetic contributions to experimental pain responses is presented, emphasizing genetic associations that have been replicated in multiple cohorts. It is hoped that an enhanced understanding of genetic contributions to pain responses will ultimately improve diagnosis and treatment of clinical pain conditions. PMID:19193196

Fillingim, RB; Wallace, MR; Herbstman, DM; Ribeiro-Dasilva, M; Staud, R



Genetic Analysis of Inherited Leukodystrophies  

PubMed Central

Importance The leukodystrophies comprise a clinically and genetically heterogeneous group of progressive hereditary neurological disorders mainly affecting the myelin in the central nervous system. Their onset is variable from childhood to adulthood and presentation can be with a variety of clinical features that include mainly for adult-onset cases cognitive decline, seizures, parkinsonism, muscle weakness, neuropathy, spastic paraplegia, personality/behavioral problems, and dystonia. Recently, Rademakers and colleagues identified mutations in the CSF1R gene as the cause of hereditary diffuse leukoencephalopathy with spheroids (HDLS), offering the possibility for an in-life diagnosis. The detection of mutations in this gene in cases diagnosed with different clinical entities further demonstrated the difficulties in the clinical diagnosis of HDLS. Objective To better understand the genetic role of mutations in this gene, we sequenced a large cohort of adult-onset leukodystrophy cases. Design Whole-exome sequencing and follow up-screening by Sanger sequencing. Setting Collaborative study between the Institute of Neurology, University College London and the Inserm, Paris, France. Participants A total of 114 probands, mostly European patients, with a diagnosis of adult-onset leukodystrophy or atypical cases that could fit within a picture of leukodystrophy. These included 3 extended families within the spectrum of leukodystrophy phenotype. Interventions Whole-exome sequencing in a family and Sanger sequencing of CSF1R. Main Outcomes and Measures Mutations in CSF1R. Results We identified 12 probands with mutations in CSF1R. The clinical diagnoses given to these patients included dementia with spastic paraplegia, corticobasal degeneration syndrome, and stroke disorders. Our study shows that CSF1R mutations are responsible for a significant proportion of clinically and pathologically proven HDLS. Conclusions and Relevance These results give an indication of the frequency of CSF1R mutations in a European leukodystrophy series and expand the phenotypic spectrum of disorders that should be screened for this gene. PMID:23649896

Bras, Jose; Rohrer, Jonathan D.; Taipa, Ricardo; Lashley, Tammaryn; Dupuits, Celine; Gurunlian, Nicole; Mochel, Fanny; Warren, Jason D.; Hannequin, Didier; Sedel, Frederic; Depienne, Christel; Camuzat, Agnes; Golfier, Veronique; Du Boisgueheneuc, Foucaud; Schottlaender, Lucia; Fox, Nick C.; Beck, Jonathan; Mead, Simon; Rossor, Martin N.; Hardy, John; Revesz, Tamas; Brice, Alexis; Houlden, Henry



Pathogenesis, diagnosis, and management of cholangiocarcinoma.  


Cholangiocarcinomas (CCAs) are hepatobiliary cancers with features of cholangiocyte differentiation; they can be classified anatomically as intrahepatic CCA (iCCA), perihilar CCA (pCCA), or distal CCA. These subtypes differ not only in their anatomic location, but in epidemiology, origin, etiology, pathogenesis, and treatment. The incidence and mortality of iCCA has been increasing over the past 3 decades, and only a low percentage of patients survive until 5 years after diagnosis. Geographic variations in the incidence of CCA are related to variations in risk factors. Changes in oncogene and inflammatory signaling pathways, as well as genetic and epigenetic alterations and chromosome aberrations, have been shown to contribute to the development of CCA. Furthermore, CCAs are surrounded by a dense stroma that contains many cancer-associated fibroblasts, which promotes their progression. We have gained a better understanding of the imaging characteristics of iCCAs and have developed advanced cytologic techniques to detect pCCAs. Patients with iCCAs usually are treated surgically, whereas liver transplantation after neoadjuvant chemoradiation is an option for a subset of patients with pCCAs. We review recent developments in our understanding of the epidemiology and pathogenesis of CCA, along with advances in classification, diagnosis, and treatment. PMID:24140396

Rizvi, Sumera; Gores, Gregory J



Prenatal diagnosis--discrimination, deliverance or democracy?  


Prenatal diagnosis utilizes invasive procedures such as amniocentesis, chorionic villus sampling, cord blood sampling and pre-implantation genetic diagnosis. These techniques can diagnose serious foetal illnesses and this therefore provides valuable information to couples, helping them to prepare for the birth of an affected child. It also affords women the freedom to decide whether to terminate a pregnancy. The selective termination of foetuses with serious disabilities does not represent disability discrimination because women and parents are actually rejecting the disability, rather than the foetus itself. More significantly, the choice to abort a foetus with a serious illness or disability is an intensely private and personal exercise that does not and cannot be reflective of a wider public morality. Exactly the same can be said of the choice to selectively abort foetuses based solely on their sex. The private choice of women in this respect does not amount to the social devaluation of women. Firstly, it is an erroneous assumption that women in Australia prefer male babies. Secondly, even if there is a preference for male babies, banning prenatal sex selection would be treating just one of many symptoms of sexism, rather than curing the primary causes. The moral right of all women to reproductive freedom is an embodiment of their equal value in society. PMID:14696609

Bradfield, Owen



Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment.  


This review focuses on advances and updates in the epidemiology, pathogenesis, diagnosis, and treatment of food allergy over the past 3 years since our last comprehensive review. On the basis of numerous studies, food allergy likely affects nearly 5% of adults and 8% of children, with growing evidence of an increase in prevalence. Potentially rectifiable risk factors include vitamin D insufficiency, unhealthful dietary fat, obesity, increased hygiene, and the timing of exposure to foods, but genetics and other lifestyle issues play a role as well. Interesting clinical insights into pathogenesis include discoveries regarding gene-environment interactions and an increasing understanding of the role of nonoral sensitizing exposures causing food allergy, such as delayed allergic reactions to carbohydrate moieties in mammalian meats caused by sensitization from homologous substances transferred during tick bites. Component-resolved diagnosis is being rapidly incorporated into clinical use, and sophisticated diagnostic tests that indicate severity and prognosis are on the horizon. Current management relies heavily on avoidance and emergency preparedness, and recent studies, guidelines, and resources provide insight into improving the safety and well-being of patients and their families. Incorporation of extensively heated (heat-denatured) forms of milk and egg into the diets of children who tolerate these foods, rather than strict avoidance, represents a significant shift in clinical approach. Recommendations about the prevention of food allergy and atopic disease through diet have changed radically, with rescinding of many recommendations about extensive and prolonged allergen avoidance. Numerous therapies have reached clinical trials, with some showing promise to dramatically alter treatment. Ongoing studies will elucidate improved prevention, diagnosis, and treatment. PMID:24388012

Sicherer, Scott H; Sampson, Hugh A



Genetic kidney diseases  

PubMed Central

Knowledge of the primary cause of a disease is essential for understanding its mechanisms and for adequate classification, prognosis, and treatment. Recently, the etiologies of many kidney diseases have been revealed as single-gene defects. This is exemplified by steroid-resistant nephrotic syndrome, which is caused by podocin mutations in ~25% of childhood and ~15% of adult cases. Knowledge of a disease-causing mutation in a single-gene disorder represents one of the most robust diagnostic examples of “personalized medicine”, because the mutation conveys an almost 100% risk of developing the disease by a certain age. Whereas single-gene diseases are rare disorders, polygenic “risk alleles” are found in common adult-onset diseases. This review will discuss prominent renal single-gene kidney disorders and polygenic risk alleles of common disorders. We delineate how emerging techniques of total exome capture and large-scale sequencing will facilitate molecular genetic diagnosis, prognosis and specific therapy and lead to a better understanding of disease mechanisms, thus enabling development of new targeted drugs. PMID:20382325

Hildebrandt, Friedhelm



Current Diagnosis and Treatment of Anxiety Disorders  

PubMed Central

Anxiety disorders are the most prevalent mental health conditions. Although they are less visible than schizophrenia, depression, and bipolar disorder, they can be just as disabling. The diagnoses of anxiety disorders are being continuously revised. Both dimensional and structural diagnoses have been used in clinical treatment and research, and both methods have been proposed for the new classification in the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-5). However, each of these approaches has limitations. More recently, the emphasis in diagnosis has focused on neuroimaging and genetic research. This approach is based partly on the need for a more comprehensive understanding of how biology, stress, and genetics interact to shape the symptoms of anxiety. Anxiety disorders can be effectively treated with psychopharmacological and cognitive–behavioral interventions. These inter ventions have different symptom targets; thus, logical combinations of these strategies need to be further studied in order to improve future outcomes. New developments are forthcoming in the field of alternative strategies for managing anxiety and for treatment-resistant cases. Additional treatment enhancements should include the development of algorithms that can be easily used in primary care and with greater focus on managing functional impairment in patients with anxiety. PMID:23599668

Bystritsky, Alexander; Khalsa, Sahib S.; Cameron, Michael E.; Schiffman, Jason



Radiological diagnosis of gallbladder disease  

SciTech Connect

Changes in the radiological diagnosis of gallbladder disease are occurring at a remarkable rate. In this symposium, several recognized authorities place the various diagnostic modalities and their interrelation in modern perspective. The present and future roles of oral cholecystography and intravenous cholangiography, the radiological diagnosis of chronic acalculous cholecystits, and the use of ultrasonography and cholescintigraphy are analyzed.

Berk, R.N. (Univ. of California, San Diego); Ferrucci, J.T.; Fordtran, J.S.



Psychosocial Approaches to Dual Diagnosis  

Microsoft Academic Search

Recent research elucidates many aspects of the problem of co-occurring substance use disorder (SUD) in patients with severe mental illness, which is often termed dual diagnosis. This paper provides a brief overview of cur- rent research on the epidemiology, adverse conse- quences, and phenomenology of dual diagnosis, followed by a more extensive review of current approaches to ser- vices, assessment,

Robert E. Drake; Kim T. Mueser



Networking in Autism: Leveraging Genetic, Biomarker and Model System Findings in the Search for New  

E-print Network

; #12; #12; #12; #12; ASD HISTORY AND DIAGNOSIS Leo Kanner initially described `early infantile autism as the positive symptoms of autism, are also required to make a diagnosis. Symptoms of autism are commonlyNetworking in Autism: Leveraging Genetic, Biomarker and Model System Findings in the Search for New

Blakely, Randy


LEOPARD syndrome: clinical dilemmas in differential diagnosis of RASopathies  

PubMed Central

Background Diagnosis within RASopathies still represents a challenge. Nevertheless, many efforts have been made by clinicians to identify specific clinical features which might help in differentiating one disorder from another. Here, we describe a child initially diagnosed with Neurofibromatosis-Noonan syndrome. The follow-up of the proband, the clinical evaluation of his father together with a gene-by-gene testing approach led us to the proper diagnosis. Case presentation We report a 8-year-old male with multiple café-au-lait macules, several lentigines and dysmorphic features that suggest Noonan syndrome initially diagnosed with Neurofibromatosis-Noonan syndrome. However, after a few years of clinical and ophthalmological follow-up, the absence of typical features of Neurofibromatosis type 1 and the lack of NF1 mutation led us to reconsider the original diagnosis. A new examination of the patient and his similarly affected father, who was initially referred as healthy, led us to suspect LEOPARD syndrome, The diagnosis was then confirmed by the occurrence in both patients of a heterozygous mutation c.1403 C?>?T, p.(Thr468Met), of PTPN11. Subsequently, the proband was also found to have type-1 Arnold-Chiari malformation in association with syringomyelia. Conclusion Our experience suggests that differential clinical diagnosis among RASopathies remains ambiguous and raises doubts on the current diagnostic clinical criteria. In some cases, genetic tests represent the only conclusive proof for a correct diagnosis and, consequently, for establishing individual prognosis and providing adequate follow-up. Thus, molecular testing represents an essential tool in differential diagnosis of RASophaties. This view is further strengthened by the increasing accessibility of new sequencing techniques. Finally, to our knowledge, the described case represents the third report of the occurrence of Arnold Chiari malformation and the second description of syringomyelia with LEOPARD syndrome. PMID:24767283



November 20, 2001 Evolutionary Genetics  

E-print Network

November 20, 2001 Evolutionary Genetics (for Encyclopedia of Biodiversity) Sergey Gavrilets-1610 USA Evolutionary genetics studies the patterns and mechanisms of genetic changes underlying evolu diversity) has a genetic basis and is a result of evolution, evolutionary genetics provides insight

Gavrilets, Sergey


Update: Biochemistry of Genetic Manipulation.  

ERIC Educational Resources Information Center

Various topics on the biochemistry of genetic manipulation are discussed. These include genetic transformation and DNA; genetic expression; DNA replication, repair, and mutation; technology of genetic manipulation; and applications of genetic manipulation. Other techniques employed are also considered. (JN)

Barker, G. R.



Genetic evidence that the “Padstow mussel” is Mytilus galloprovincialis  

Microsoft Academic Search

Electrophoretic analysis of loci controlling a variety of enzymes has been applied to samples of the “Padstow mussel” and typical Mytilus edulis L. living strictly sympatrically at Rock, Cornwall, England, in order to resolve the disputed status of the “Padstow mussel”. Small samples indicated similar monomorphic states at the aGPDH, TO, MDH-2 loci and weak polymorphism at the 6 PGD

Mahmud Ahmad; J. A. Beardmore



Sequential Diagnosis: Decision Tree and Minimal Entropy  

E-print Network

Sequential Diagnosis: Decision Tree and Minimal Entropy 16.410-13 Lecture 25 Peng Yu December 12th, 2011 Lecture 25: Sequential Diagnosis 1 #12;· No more problem sets and projects! · Review session: Sequential Diagnosis 2 #12;· Diagnosis Algorithm Review. · Active Probing and Sequential Diagnosis

Williams, Brian C.


Hypertrophic cardiomyopathy: from genetics to treatment  

PubMed Central

Background Hypertrophic cardiomyopathy (HCM) is the prototypic form of pathological cardiac hypertrophy. HCM is an important cause of sudden cardiac death in the young and a major cause of morbidity in the elderly. Design We discuss the clinical implications of recent advances in the molecular genetics of HCM. Results The current diagnosis of HCM is neither adequately sensitive nor specific. Partial elucidation of the molecular genetic basis of HCM has raised interest in genetic-based diagnosis and management. Over a dozen causal genes have been identified. MYH7 and MYBPC3 mutations account for about 50% of cases. The remaining known causal genes are uncommon and some are rare. Advances in DNA sequencing techniques have made genetic screening practical. The difficulty, particularly in the sporadic cases and in small families, is to discern the causal from the non-causal variants. Overall, the causal mutations alone have limited implications in risk stratification and prognostication, as the clinical phenotype arises from complex and often non-linear interactions between various determinants. Conclusions The clinical phenotype of ‘HCM’ results from mutations in sarcomeric proteins and subsequent activation of multiple cellular constituents including signal transducers. We advocate that HCM, despite its current recognition and management as a single disease entity, involves multiple partially independent mechanisms, despite similarity in the ensuing phenotype. To treat HCM effectively, it is necessary to delineate the underlying fundamental mechanisms that govern the pathogenesis of the phenotype and apply these principles to the treatment of each subset of clinically recognized HCM. PMID:20503496

Marian, Ali J.



Myxoinflammatory fibroblastic sarcoma: morphologic and genetic updates.  


Myxoinflammatory fibroblastic sarcoma (MIFS) is a malignant mesenchymal neoplasm most frequently arising in the distal extremities of adults, which usually behaves in a low-grade manner but is capable of metastasizing to local and distant sites, rarely leading to death. It is a rare tumor whose unusual morphology can lead to erroneous histologic diagnosis, either as a nonneoplastic (infectious or inflammatory) process or as a variety of neoplastic diseases. While its exact origin is uncertain, ultrastructural studies have shown at least some of the constituent cells to be modified fibroblasts. Distinct and reproducible genetic abnormalities identified in MIFS are translocation t(1;10)(p22:q24), with rearrangements of the TGFBR3 and MGEA5 genes associated with increased levels of FGF8, and formation of marker/ring chromosome 3, with amplification of the VGLL3 locus. Because these genetic abnormalities are shared by both MIFS and hemosiderotic fibrohistiocytic lipomatous tumor, it is thought that these 2 morphologically distinct neoplasms may comprise a spectrum of disease defined by these genetics. We review the literature on MIFS and discuss morphology (including that of MIFS/hemosiderotic fibrohistiocytic lipomatous tumor hybrid lesions), immunohistochemistry, the differential diagnosis, and recent molecular genetic developments. PMID:25268202

Ieremia, Eleni; Thway, Khin



Bronchoscopic diagnosis of pneumonia.  

PubMed Central

Lower respiratory tract infections are characterized by significant morbidity and mortality but also by a relative inability to establish a specific etiologic agent on clinical grounds alone. With the recognized shortcomings of expectorated or aspirated secretions toward establishing an etiologic diagnosis, clinicians have increasingly used bronchoscopy to obtain diagnostic samples. A variety of specimen types may be obtained, including bronchial washes or brushes, protected specimen brushings, bronchoalveolar lavage, and transbronchial biopsies. Bronchoscopy has been applied in three primary clinical settings, including the immunocompromised host, especially human immunodeficiency virus-infected and organ transplant patients; ventilator-associated pneumonia; and severe, nonresolving community- or hospital-acquired pneumonia in nonventilated patients. In each clinical setting, and for each specimen type, specific laboratory protocols are required to provide maximal information. These protocols should provide for the use of a variety of rapid microscopic and quantitative culture techniques and the use of a variety of specific stains and selective culture to detect unusual organism groups. PMID:7834604

Baselski, V S; Wunderink, R G



Hematospermia: diagnosis and treatment.  


The presence of blood in ejaculate represents 1% of all andrologic and urologic symptoms. In most cases it has a benign character and tends to regress spontaneously after the first episode. But in the same case it can be caused by bladder-prostate or systemic malignant patology, so it is necessary to subject the patient to laboratory and instrumental tests in order to find the best treatment that, as for hematospermia, is an etiological one. Most important for correct diagnosis are patient history, physical examination, laboratory tests, transrectal ultrasound examination of the prostate, MRI, CT, cistoscopy. Hematospermia is rarely associated with significant pathology, especially in younger men. The 3 factors that dictate the extent of the evaluation and treatment are patients age, the duration and recurrence of the hematospermia, and the presence of any associated hematuria. So it is possible to distinguish idiopathic from secondary hematospermia, because secondary hematospermia, i.e. the one in which the bleeding cause is known or suspected, requires an etiologic treatment. Urologists must make rational decisions based on evidence rather than practice defensive medicine. Understanding the pathophysiology and prevalence in populations of different ages helps minimize the likelihood of problems. When in doubt, performing a TRUS, cystoscopy, and basic laboratory analyses limits exposure. PMID:16929612

Polito, Massimo; Giannubilo, Willy; d'Anzeo, Gianluca; Muzzonigro, Giovanni



[Diagnosis of extrauterine pregnancy].  


In pregnancies, the incidence of ectopic pregnancy varies from 1.2% to 1.4%. Diagnostic management of ectopic pregnancy is made by biochemical and ultrasonographic analysis. The evaluation of symptoms and anamnesis improves both comprehension and evaluation of technical data. This review analyzed the risk factors most commonly reported in women with ectopic pregnancy. According to the literature, the improvement of biochemical knowledge has determined the study of many substances: beta hCG, specific glycoproteins beta 1, creatine kinase, renine, progesterone. Transvaginal ultrasound examination presents different specificity and sensitivity. When ultrasonic imagining is not clear, it is useful to study uterine and adnexal vascularization by color Doppler and pulsed Doppler. The majority of authors consider laparoscopy as a gold standard for diagnosing an ectopic pregnancy. The endoscopic approach has multiple advantages: it could be in the same time diagnostic and therapeutic. The curettage of uterine cavity has been proposed as a diagnostic tool for analyzing by frozen section the presence or not of chorial villi. In personal opinion, an easy and simple diagnostic management should involve the clinical, biochemical and ultrasonographic procedures. Laparoscopy should be the last step in order to confirm a diagnosis and to establish the best therapeutical approach. PMID:10230240

Giambanco, V; Giambanco, L; Alaimo, D



Serologic diagnosis of NMO  

PubMed Central

Objectives: Neuromyelitis optica (NMO) immunoglobulin G (IgG) (aquaporin-4 [AQP4] IgG) is highly specific for NMO and related disorders, and autoantibody detection has become an essential investigation in patients with demyelinating disease. However, although different techniques are now used, no multicenter comparisons have been performed. This study compares the sensitivity and specificity of different assays, including an in-house flow cytometric assay and 2 commercial assays (ELISA and transfected cell-based assay [CBA]). Methods: Six assay methods (in-house or commercial) were performed in 2 international centers using coded serum from patients with NMO (35 patients), NMO spectrum disorders (25 patients), relapsing-remitting multiple sclerosis (39 patients), miscellaneous autoimmune diseases (25 patients), and healthy subjects (22 subjects). Results: The highest sensitivities were yielded by assays detecting IgG binding to cells expressing recombinant AQP4 with quantitative flow cytometry (77; 46 of 60) or visual observation (CBA, 73%; 44 of 60). The fluorescence immunoprecipitation assay and tissue-based immunofluorescence assay were least sensitive (48%–53%). The CBA and ELISA commercial assays (100% specific) yielded sensitivities of 68% (41 of 60) and 60% (36 of 60), respectively, and sensitivity of 72% (43 of 60) when used in combination. Conclusions: The greater sensitivity and excellent specificity of second-generation recombinant antigen-based assays for detection of NMO-IgG in a clinical setting should enable earlier diagnosis of NMO spectrum disorders and prompt initiation of disease-appropriate therapies. PMID:22302543

McKeon, A.; Leite, M.I.; Rajasekharan, S.; Lennon, V.A.; Villalobos, A.; Palace, J.; Mandrekar, J.N.; Vincent, A.; Bar-Or, A.



Principles of well diagnosis  

SciTech Connect

Well performance analysis provides an effective engineering resource for the analysis of well problems and the benefit possible from well workovers or well stimulation to improve well performance. Transient pressure testing and analysis has long been used to identify formation potential and to disclose wellbore restrictions; however, this methodology does not identify the source of restricted flow or a realistic potential of a well completion change. Well diagnosis not only involves pressure transient testing and analysis, but also well completion procedure analysis, well log analysis, special petrographic analysis, and flowing well system analysis (often called Nodal Analysis). Although reservoir flow and tubular flow are important in this systems analysis, well completion modeling is often the key to improvements through workover or stimulation. Several completion or wellbore models have been developed and presented in the last 20 years. Those models dealing with perforated wells and gravel packed wells will be reviewed and illustrated with case histories that demonstrate how well systems analysis leads to improved well performance. The geology of the formation is often critical in the analysis of formation damage and interpretation of well production problems, especially when flow is not sufficient to allow pressure transient testing. Well completion operation analysis is a developing art which incorporates an understanding of the latest research and a familiarity with field practice, and a strategy for this analysis will be provided.

McLeod, H.O.



Avian toxicologic diagnosis  

USGS Publications Warehouse

This chapter describes the sources and pathophysiology of some potential poisons that affect birds and summarizes useful laboratory tests. The diagnosis of poisoning in birds, as in mammals, requires a complete and accurate history, careful observation of clinical signs, and a thorough necropsy evaluation. Appropriate sample handling and analysis, based on consultation with the diagnostic toxicologist, are critical (Table 19--1). Veterinary toxicology laboratories are becoming increasingly specialized, with only certain laboratories capable of analyzing for drug residues or anticoagulants, for example. Although a local laboratory may not be able to fulfill a specific test request, they may recommend an alternative laboratory or may be willing to forward the sample. As a general rule in suspect poisoning cases, large tissue samples of liver, kidney, brain, and subcutaneous fat and of crop, proventriculus, and ventriculus contents should be collected at necropsy and frozen. Appropriate samples should be submitted frozen, with the remainder held in the freezer for possible later testing. A second set of tissues should be placed in 10% formalin for histopathologic examination.

Sigurdson, C. J.; Franson, J. C.



Acute Stroke Diagnosis  

PubMed Central

Stroke can be categorized as ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Awakening with or experiencing the abrupt onset of focal neurologic deficits is the