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Sample records for genetic diagnosis pgd

  1. Knowledge and Educational Needs about Pre-Implantation Genetic Diagnosis (PGD) among Oncology Nurses

    PubMed Central

    Quinn, Gwendolyn P.; Knapp, Caprice; Sehovic, Ivana; Ung, Danielle; Bowman, Meghan; Gonzalez, Luis; Vadaparampil, Susan T.

    2014-01-01

    Preimplantation genetic diagnosis (PGD), a form of assisted reproductive technology, is a new technology with limited awareness among health care professionals and hereditary cancer families. Nurses play a key role in the care of patients and are often in an ideal position to discuss and refer patients on sensitive quality of life issues, such as PGD. Two hundred and one nurses at Moffitt Cancer Center (MCC) responded to an online survey assessing knowledge and educational needs regarding PGD and families with hereditary cancer. The majority of respondents were female (n = 188), white (n = 175), had an RN/BSN degree (n = 83), and provided outpatient care at the cancer center (n = 102). More than half of respondents (78%) were unfamiliar with PGD prior to the survey and respondents who had heard of PGD had limited knowledge. More than half of the participants reported PGD was an acceptable option for families with hereditary cancer syndromes and thought individuals with a strong family or personal history should be provided with information about PGD. This study indicates that oncology nurses may benefit from and desire education about PGD. With advances in reproductive technology and options, further PGD education is needed among healthcare professionals. An examination of current oncology nursing curriculum and competencies regarding genetic education may identify need for future revisions and updates. PMID:26237394

  2. Knowledge and Educational Needs about Pre-Implantation Genetic Diagnosis (PGD) among Oncology Nurses.

    PubMed

    Quinn, Gwendolyn P; Knapp, Caprice; Sehovic, Ivana; Ung, Danielle; Bowman, Meghan; Gonzalez, Luis; Vadaparampil, Susan T

    2014-01-01

    Preimplantation genetic diagnosis (PGD), a form of assisted reproductive technology, is a new technology with limited awareness among health care professionals and hereditary cancer families. Nurses play a key role in the care of patients and are often in an ideal position to discuss and refer patients on sensitive quality of life issues, such as PGD. Two hundred and one nurses at Moffitt Cancer Center (MCC) responded to an online survey assessing knowledge and educational needs regarding PGD and families with hereditary cancer. The majority of respondents were female (n = 188), white (n = 175), had an RN/BSN degree (n = 83), and provided outpatient care at the cancer center (n = 102). More than half of respondents (78%) were unfamiliar with PGD prior to the survey and respondents who had heard of PGD had limited knowledge. More than half of the participants reported PGD was an acceptable option for families with hereditary cancer syndromes and thought individuals with a strong family or personal history should be provided with information about PGD. This study indicates that oncology nurses may benefit from and desire education about PGD. With advances in reproductive technology and options, further PGD education is needed among healthcare professionals. An examination of current oncology nursing curriculum and competencies regarding genetic education may identify need for future revisions and updates. PMID:26237394

  3. ESHRE Preimplantation Genetic Diagnosis (PGD) Consortium: preliminary assessment of data from January 1997 to September 1998. ESHRE PGD Consortium Steering Committee.

    PubMed

    Geraedts, J; Handyside, A; Harper, J; Liebaers, I; Sermon, K; Staessen, C; Thornhill, A; Vanderfaeillie, A; Viville, S

    1999-12-01

    The first clinical application of preimplantation genetic diagnosis (PGD) was reported almost a decade ago. Since then, the range of genetic defects that can be detected at single cell level has increased dramatically. At the 13th Annual Meeting of ESHRE in Edinburgh in 1997, a PGD Consortium was formed to undertake the first systematic and long-term study of the efficacy and clinical outcome of PGD. We report here the first data collection covering the period of January 1997 to September 1998. Referral data on 323 couples have been collected for a variety of monogenic and chromosomal disorders, providing information about which patients, at risk for which genetic diseases, are interested in PGD. Data were collected on 392 PGD cycles, resulting in 302 embryo transfers and 66 clinical pregnancies. Because of the importance of follow-up of the children born after PGD, participating centres were asked to contribute data on the pregnancies achieved and the children born after PGD since the start of their PGD programme. Data on 82 pregnancies and 110 fetal sacs were collected, and information was available on 79 children. Finally, biopsy, fluorescence in-situ hybridization and polymerase chain reaction protocols were collected, clearly showing that no consensus exists on technical aspects such as which culture medium to use, and emphasizing the role the PGD Consortium could play in setting up guidelines for good laboratory practice. In conclusion, it is clear that the effort of gathering data on PGD cycles is worthwhile and will be continued in the future, preferably using electronic data collection. PMID:10601110

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

    PubMed Central

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

    2010-01-01

    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

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

    SciTech Connect

    Verlinsky, Y.; Strom, C.; Rechitsky, S.

    1994-09-01

    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.

  6. [Preimplantation diagnosis--PID: preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS)].

    PubMed

    Montag, M; Toth, B; Strowitzki, T

    2013-12-01

    Preimplantation diagnosis (PID) comprises all the relevant diagnostic procedures for the investigation of genetic, structural, or numerical changes of the genetic information in spermatozoa and oocytes as well as in embryos after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). PID of oocytes is well established in Germany for the above-mentioned indications. PID at the embryonic level, i.e., trophectoderm biopsy of blastocysts, is possible in centers with proven expertise in reproductive medicine and human genetics. A high risk for genetic disease in the child or a high likelihood for stillbirth or miscarriage is a prerequisite for PID. A specialized ethics committee is required to look into each case before making a decision. While PID is still under development in Germany, it has been a well-established technology worldwide for 24 years. International experience in PID and the resulting implications are discussed in this article. PMID:24337129

  7. Media debates and 'ethical publicity' on social sex selection through preimplantation genetic diagnosis (PGD) technology in Australia.

    PubMed

    Whittaker, Andrea

    2015-01-01

    This paper offers a critical discourse analysis of media debate over social sex selection in the Australian media from 2008 to 2014. This period coincides with a review of the National Health and Medical Research Council's Ethical Guidelines on the Use of Assisted Reproductive Technology in Clinical Practice and Research (2007), which underlie the regulation of assisted reproductive clinics and practice in Australia. I examine the discussion of the ethics of pre-implatation genetic diagnosis (PGD) within the media as 'ethical publicity' to the lay public. Sex selection through PGD is both exemplary of and interconnected with a range of debates in Australia about the legitimacy of certain reproductive choices and the extent to which procreative liberties should be restricted. Major themes emerging from media reports on PGD sex selection in Australia are described. These include: the spectre of science out of control; ramifications for the contestation over the public funding of abortion in Australia; private choices versus public authorities regulating reproduction; and the ethics of travelling overseas for the technology. It is concluded that within Australia, the issue of PGD sex selection is framed in terms of questions of individual freedom against the principle of sex discrimination - a principle enshrined in legislation - and a commitment to publically-funded medical care. PMID:25803702

  8. Benefits and drawbacks of preimplantation genetic diagnosis (PGD) for reciprocal translocations: lessons from a prospective cohort study.

    PubMed

    Scriven, Paul N; Flinter, Frances A; Khalaf, Yakoub; Lashwood, Alison; Mackie Ogilvie, Caroline

    2013-10-01

    Preimplantation genetic diagnosis (PGD) using fluorescence in situ hybridisation probes was carried out for 59 couples carrying reciprocal translocations. Before treatment, 85% of pregnancies had resulted in spontaneous miscarriage and five couples had achieved a healthy live-birth delivery. Following treatment, 33% of pregnancies failed and 21 of 59 couples had a healthy live-born child. The accuracy of diagnosis was 92% (8% false abnormal and 0% false normal results). The overall incidence of 2:2 alternate segregation products was 44%; however, products consistent with 2:2 adjacent segregation were ~twice as likely from male heterozygotes, and those with 3:1 disjunction were three times more likely from female heterozygotes. Our results indicate that up to three stimulation cycles per couple would give an ~50% chance of a successful live birth, with the risk of miscarriage reduced to the level found in the general population. In our study, 87% of all normal/balanced embryos available were identified as being suitable for transfer. We conclude that PGD provides benefit for couples with high-risk translocations by reducing the risk of miscarriage and avoiding a pregnancy with an unbalanced form of the translocation; however, for fertile carriers of translocations with a low risk of conceiving a chromosomally unbalanced offspring, natural conception may be a more viable option. PMID:23386032

  9. [The physician's role in various clinical contexts. Physician counseling on in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD)].

    PubMed

    Kentenich, H; Tandler-Schneider, A

    2012-09-01

    The role of the physician in the context of in vitro fertilization and preimplantation genetic diagnosis has certain distinct characteristics. Involuntary childlessness by definition of the WHO is a disease with good treatment options. As it is not considered a medical emergency, the focus lies more on intensive information giving, education, and counseling. Because the diagnosis and treatment can be a medical and psychological strain for the couple, counseling should address both medical and psychological aspects. The physician needs to have detailed medical knowledge as well as good communication skills to be able to meet the specific needs of the couple. Moreover, the physician should point out the realistic success rates of treatment and should refer to alternatives, such as remaining childless, adoption, and sperm or egg donation. The concurrent inclusion of biological, psychological, social, and ethical aspects in terms of psychosomatic basic care (Psychosomatische Grundversorgung) seems to be useful. There is potential for conflicts, for example, due to the economic interests of the physician. On the other hand, the treatment can be a financial burden for the couple. Of importance are the physician's and the patient's moral concepts, especially concerning some aspects of therapy (sperm and egg donation, surrogacy). The expected welfare of the intended child should also be respected (e.g., higher risk of preterm birth in multiple pregnancies). Further possible conflicts in reproductive medicine arise because of the crossing of moral boundaries (oocyte donation for postmenopausal women, surrogacy, cloning of human beings). The framework of counseling is based on the guidelines of the German Medical Association (Bundesärztekammer) for assisted reproduction (2006). Preimplantation genetic diagnosis has special requirements from a medical and psychosocial point of view. PMID:22936482

  10. Pregnancy and Birth After a Two-Step PGD: Polar Body Diagnosis for Hemophilia A and Array CGH on Trophectoderm Cells for Chromosomal Aberrations

    PubMed Central

    Würfel, W.; Suttner, R.; Shakeshaft, D.; Mayer, V.; Schoen, U.; Sendelbach, K.; Locher, M.; Koehler, U.; Fiedler, K.; Krüsmann, G.; Holinski-Feder, E.

    2013-01-01

    Objective: To demonstrate that a PGD program can be successfully established after the 2011 verdict of the German Bundestag concerning PGD. Material and Method: Eight years previously, the couple had had a daughter who suffered from clinically manifest hemophilia A due to an unbalanced X-inactivation, as well as microdeletion syndrome resulting in severe physical and mental disability. The couple wished to have a second child but refused the idea of a “trial” pregnancy. Given the indications for both, it was necessary to carry out polar body diagnosis (PBD) to rule out hemophilia A and, during the same cycle, a subsequent PGD on the blastocysts to rule out genetic aberrations. The PBD and PGD (trophectoderm biopsy, TEB) were performed after high-dosage ovarian stimulation and ICSI fertilization of the oocytes. A blastocyst was successfully transferred on day 6. Results: The patient conceived immediately. The pregnancy developed normally and the patient gave birth to a girl in the 40th week of pregnancy. Post-natal examinations showed that the baby is free from hemophilia A and is developing normally both physically and mentally. Conclusion: Establishment of a PGD program is now possible after legalization of PGD in Germany. It is possible to apply two investigative techniques in a single treatment cycle if multifactorial diagnosis is required. PMID:24771936

  11. Cultural Concerns when Counseling Orthodox Jewish Couples for Genetic Screening and PGD.

    PubMed

    Grazi, Richard V; Wolowelsky, Joel B

    2015-12-01

    There is a spectrum of attitudes within the Orthodox Jewish community towards genetic testing and PGD. Increased understanding of the belief systems of the Orthodox Jewish population will enhance the genetic counselors' ability to better serve this unique group of patients. By improving cultural competence, genetic counselors can help patients choose the testing options that they deem appropriate, while simultaneously respecting the patient's belief system. PMID:26174938

  12. [Genetic diagnosis of the embryo before implantation].

    PubMed

    David, G

    1997-02-01

    The association of recent progress in two initially faraway fields, assisted reproductive technology and molecular biology, has made way for the preimplantation genetic diagnosis (PGD). For some people this new technique was, immediately, considered as an alternative to prenatal diagnosis for couples at risk of offspring affected with severe genetic diseases. This technique has the advantage of avoiding an eventual abortion and replacing it by an in vitro embryos preselection. For others PGD appeared, above all, as matter of new eugenic risk. In fact, these excessive hopes and fears have contributed to blurring the true current problems of PGD, technical difficulties and still limited reliability. While the French law has admitted the principle of PGD use, the measures for its application remain to be defined. But this legal authorization must recognize that this new technique will be, for a long time, at the stage of research, improvement and assessment. PMID:9235226

  13. Reproductive management through integration of PGD and MPS-based noninvasive prenatal screening/diagnosis for a family with GJB2-associated hearing impairment.

    PubMed

    Xiong, WenPing; Wang, DaYong; Gao, Yuan; Gao, Ya; Wang, HongYang; Guan, Jing; Lan, Lan; Yan, JunHao; Zong, Liang; Yuan, Yuan; Dong, Wei; Huang, SeXin; Wu, KeLiang; Wang, YaoShen; Wang, ZhiLi; Peng, HongMei; Lu, YanPing; Xie, LinYi; Zhao, Cui; Wang, Li; Zhang, QiuJing; Gao, Yun; Li, Na; Yang, Ju; Yin, ZiFang; Han, Bing; Wang, Wei; Chen, Zi-Jiang; Wang, QiuJu

    2015-09-01

    A couple with a proband child of GJB2 (encoding the gap junction protein connexin 26)-associated hearing impairment and a previous pregnancy miscarriage sought for a reproductive solution to bear a healthy child. Our study aimed to develop a customized preconception-to-neonate care trajectory to fulfill this clinical demand by integrating preimplantation genetic diagnosis (PGD), noninvasive prenatal testing (NIPT), and noninvasive prenatal diagnosis (NIPD) into the strategy. Auditory and genetic diagnosis of the proband child was carried out to identify the disease causative mutations. The couple then received in-vitro-fertilization treatment, and eight embryos were obtained for day 5 biopsy. PGD was performed by short-tandem-repeat linkage analysis and Sanger sequencing of GJB2 gene. Transfer of a GJB2c.235delC heterozygous embryo resulted in a singleton pregnancy. At the 13th week of gestation, genomic DNA (gDNA) from the trio family and cell-free DNA (cfDNA) from maternal plasma were obtained for assessment of fetal chromosomal aneuploidy and GJB2 mutations. NIPT and NIPD showed the absence of chromosomal aneuploidy and GJB2-associated disease in the fetus, which was later confirmed by invasive procedures and postnatal genetic/auditory diagnosis. This strategy successfully prevented the transmission of hearing impairment in the newborn, thus providing a valuable experience in reproductive management of similar cases and potentially other monogenic disorders. PMID:26432548

  14. Jewish perspectives on the use of preimplantation genetic diagnosis.

    PubMed

    Popovsky, Mark

    2007-01-01

    This article presents an analysis of the ethical considerations raised by preimplantation genetic diagnosis (PGD) from a Jewish perspective. It weighs the Jewish imperatives to pursue good health against a number of harms that may follow from the expanded use of PGD technology, including increased medical risk to the mother, the destruction of embryos and possible emotional harm to the child born from this procedure. It pays special attention to the potential harms that may befall those in society who do not have access to PGD or who choose not to employ it. PMID:18076520

  15. Current status of preimplantation genetic diagnosis in Japan

    PubMed Central

    Sato, Kenji; Sueoka, Kou; Iino, Kotaro; Senba, Hiroshi; Suzuki, Mariko; Mizuguchi, Yuki; Izumi, Yoko; Sato, Suguru; Nakabayashi, Akira; Tanaka, Mamoru

    2015-01-01

    This is a retrospective study aimingto clarify the current status of preimplantation genetic diagnosis (PGD) in Japan. Our data were collected from 12 facilities between September 2004 and September 2012, and entered into a database. A majority of PGD in Japan was performed for balanced structural chromosomal abnormalities in couples with recurrent miscarriage. PGD for monogenic diseases was performed only in two facilities. The average maternal age was 38 years for monogenic diseases and 40 years for chromosomal abnormalities. Overall there have been671 cycles to oocyte retrieval reported. Of these cycles, 85% (572 cycles)were for chromosomal abnormalities, and 15% (99 cycles) for monogenic diseases. Diagnosis rates in the current study were 70.8% for monogenic diseases and 94.0% for chromosomal abnormalities. Rates of embryo transfer of PGD were 62.7% for monogenic diseases and 25.5% for chromosomal abnormalities. Clinical pregnancy rates per embryo transfer were 12.0% for monogenic diseases and 35.6% for chromosomal abnormalities. Our study is the first PGD report from all facilities which had the approval of the ethics committee of the Japanese Society of Obstetrics and Gynecology. We have built a basis for gathering continuous PGD data in Japan. PMID:26124570

  16. Practices and ethical concerns regarding preimplantation diagnosis. Who regulates preimplantation genetic diagnosis in Brazil?

    PubMed Central

    Damian, B.B.; Bonetti, T.C.S.; Horovitz, D.D.G.

    2014-01-01

    Preimplantation genetic diagnosis (PGD) was originally developed to diagnose embryo-related genetic abnormalities for couples who present a high risk of a specific inherited disorder. Because this technology involves embryo selection, the medical, bioethical, and legal implications of the technique have been debated, particularly when it is used to select features that are not related to serious diseases. Although several initiatives have attempted to achieve regulatory harmonization, the diversity of healthcare services available and the presence of cultural differences have hampered attempts to achieve this goal. Thus, in different countries, the provision of PGD and regulatory frameworks reflect the perceptions of scientific groups, legislators, and society regarding this technology. In Brazil, several texts have been analyzed by the National Congress to regulate the use of assisted reproduction technologies. Legislative debates, however, are not conclusive, and limited information has been published on how PGD is specifically regulated. The country requires the development of new regulatory standards to ensure adequate access to this technology and to guarantee its safe practice. This study examined official documents published on PGD regulation in Brazil and demonstrated how little direct oversight of PGD currently exists. It provides relevant information to encourage reflection on a particular regulation model in a Brazilian context, and should serve as part of the basis to enable further reform of the clinical practice of PGD in the country. PMID:25493379

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

    PubMed

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

    2008-01-01

    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

  18. Clinical guidelines for IVF with PGD for HLA matching.

    PubMed

    Tur-Kaspa, Ilan; Jeelani, Roohi

    2015-02-01

    Preimplantation genetic diagnosis (PGD) for human leukocyte antigen (HLA) typing is an established procedure for conceiving a child who may donate cord blood or haematopoietic stem cells for transplantation to save an ill sibling. Haematopoietic stem cell transplantation (HSCT) from related matched donors improves overall survival compared with unrelated or non-matched donors. Since HSCT from related matched-donors is unavailable for 70% of patients, IVF for PGD-HLA is a relevant clinical option. Recent success of HSCT after PGD-HLA, and excellent health and family support of the children born, suggests that debate over this kind of 'designer baby' and 'gift of life' should subside. Discussions about IVF for PGD-HLA should be held with families when a related matched-donor is unavailable, when HSCT can wait at least 9-12 months, within weeks of diagnosis irrespective of prognosis, and when the mother is of reproductive age. Related half-matched egg donors may also be considered. National and international collaborations should be established, and couples choosing this modality should be referred to experienced IVF and PGD centres. Clinical guidelines will improve physician and patient awareness of IVF for PGD-HLA and its role in advancing the clinical care of children in need of HSCT. PMID:25500181

  19. Preimplantation genetic diagnosis and rational choice under risk or uncertainty.

    PubMed

    Zuradzki, Tomasz

    2014-11-01

    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

  20. Aberrant epigenetic modification in murine brain tissues of offspring from preimplantation genetic diagnosis blastomere biopsies.

    PubMed

    Zhao, Hong-Cui; Zhao, Yue; Li, Min; Yan, Jie; Li, Li; Li, Rong; Liu, Ping; Yu, Yang; Qiao, Jie

    2013-11-01

    Preimplantation genetic diagnosis (PGD) has been prevalent in the field of assisted reproductive technology, yet the long-term risks of PGD to offspring remain unknown. In the present study, the early development of PGD embryos, postimplantation characteristics, and birth rate following PGD were determined. Moreover, the behavior of the offspring conceived from the biopsied embryos was evaluated with the Morris water maze and pole climbing tests. Finally, the epigenetic modification of the global genome and methylation patterns for the H19, Igf2, and Snrpn imprinted genes were identified. The results indicated a significant delay in the blastocoel formation of PGD embryos and a decrease in the implantation ability of these embryos, which was related to the decreased number of cells in the PGD blastocysts. The PGD mice spent more time on both the nontrained quadrant of the water maze and climbing down the pole. Furthermore, the 5-hydroxymethylcytosine content in the brain tissues of PGD mice was significantly increased, but no difference was found in 5-methylcytosine content. The differentially methylated regions of H19/Igf2 exhibited decreased methylation patterns, but that of Snrpn was normal, compared to the control group. Quantitative RT-PCR indicated that Igf2 mRNA expression was significantly decreased but that H19 and Snrpn mRNAs were expressed normally. In conclusion, blastomere biopsies in PGD procedures carry potential risks to embryo development and the behavior of resulting offspring; these risks may arise from aberrant epigenetic modification and methylation patterns in brain tissues. Further studies are needed to better understand the risks associated with PGD. PMID:24089199

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

    PubMed Central

    Theodosiou, Anastasia A.; Johnson, Martin H.

    2011-01-01

    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

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

    PubMed

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

    2011-01-01

    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

  3. Complexities in reproductive choice: medical professionals' attitudes to and experiences of pre-implantation genetic diagnosis.

    PubMed

    Zeiler, Kristin

    2007-09-01

    Studies have been made on attitudes to and experiences of women and men who have undergone pre-implantation genetic diagnosis (PGD), or who are regarded as potential users of this diagnostic method. Few studies have been conducted regarding the attitudes to and experiences of medical professionals as regards PGD. This paper reports on findings from such a qualitative study in which 18 semi-structured interviews were performed with geneticists and gynaecologists in Italy, Sweden and the UK. Interviewees emphasized, among other things, the importance of choice provision. Interviewees also told stories that indicated the many ways through which choice was feared to be hampered - or was hampered. A similar emphasis on the importance of PGD as one more alternative to choose between, for 'high-risk' couples, is not found in studies on the experiences, attitudes and views of potential, or actual, users of PGD. PMID:17786649

  4. Preimplantation genetic diagnosis for myotonic dystrophy type 1: upon request to child

    PubMed Central

    De Rademaeker, Marjan; Verpoest, Willem; De Rycke, Martine; Seneca, Sara; Sermon, Karen; Desmyttere, Sonja; Bonduelle, Maryse; Van der Elst, Josianne; Devroey, Paul; Liebaers, Inge

    2009-01-01

    Preimplantation genetic diagnosis (PGD) is an alternative to prenatal diagnosis for patients at risk of transmitting an inherited disease such as myotonic dystrophy type 1(DM1) to their offspring. In this paper, the clinical application of preimplantation diagnosis for DM1 upon request to children born is described in a large cohort of risk couples. PGD could be offered to all 78 couples opting for PGD regardless of the triplet repeat size. The incidence of major complications was minimalised following a careful assessment in affected DM1 females anticipating possible cardiological, obstetrical and anaesthetical problems. A live-birth delivery rate per cycle with oocyte retrieval of 20% was the outcome. Forty-eight of the 49 children born are in good health and have normal psychomotor development. PMID:19367318

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

    PubMed

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

    2013-01-01

    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

  6. Simultaneous preimplantation genetic diagnosis for Tay-Sachs and Gaucher disease.

    PubMed

    Altarescu, Gheona; Brooks, Barry; Margalioth, Ehud; Eldar Geva, Talia; Levy-Lahad, Ephrat; Renbaum, Paul

    2007-07-01

    Preimplantation genetic diagnosis (PGD) for single gene defects is described for a family in which each parent is a carrier of both Tay-Sachs (TS) and Gaucher disease (GD). A multiplex fluorescent polymerase chain reaction protocol was developed that simultaneously amplified all four familial mutations and 10 informative microsatellite markers. In one PGD cycle, seven blastomeres were analysed, reaching a conclusive diagnosis in six out of seven embryos for TS and in five out of seven embryos for GD. Of the six diagnosed embryos, one was wild type for both TS and GD, and three were wild type for GD and carriers of TS. Two remaining embryos were compound heterozygotes for TS. Two transferable embryos developed into blastocysts (wt/wt and wt GD/carrier TS) and both were transferred on day 5. This single cycle of PGD resulted in a healthy live child. Allele drop-out (ADO) was observed in three of 34 reactions, yielding an 8% ADO rate. The occurrence of ADO in single cell analysis and undetected recombination events are primary causes of misdiagnosis in PGD and emphasize the need to use multiple polymorphic markers. So far as is known, this is the first report of concomitant PGD for two frequent Ashkenazi Jewish recessive disorders. PMID:17623543

  7. Preimplantation Genetic Diagnosis and Natural Conception: A Comparison of Live Birth Rates in Patients with Recurrent Pregnancy Loss Associated with Translocation

    PubMed Central

    Sugiura-Ogasawara, Mayumi; Nagayoshi, Motoi; Tanaka, Atsushi; Takeda, Satoru

    2015-01-01

    Background Established causes of recurrent pregnancy loss (RPL) include antiphospholipid syndrome, uterine anomalies, parental chromosomal abnormalities, particularly translocations, and abnormal embryonic karyotypes. The number of centers performing preimplantation genetic diagnosis (PGD) for patients with translocations has steadily increased worldwide. The live birth rate with PGD was reported to be 27-54%. The live birth rate with natural conception was reported to be 37-63% on the first trial and 65-83% cumulatively. To date, however, there has been no cohort study comparing age and the number of previous miscarriages in matched patients undergoing or not undergoing PGD. Thus, we compared the live birth rate of patients with RPL associated with a translocation undergoing PGD with that of patients who chose natural conception. Methods and Findings After genetic counseling, 52 patients who desired natural conception and 37 patients who chose PGD were matched for age and number of previous miscarriages and these comprised the subjects of our study. PGD was performed by means of fluorescence in situ hybridization analysis. The live birth rates on the first PGD trial and the first natural pregnancy after ascertainment of the carrier status were 37.8% and 53.8%, respectively (odds ratio 0.52, 95% confidence interval 0.22-1.23). Cumulative live birth rates were 67.6% and 65.4%, respectively, in the groups undergoing and not undergoing PGD. The time required to become pregnancy was similar in both groups. PGD was found to reduce the miscarriage rate significantly. The prevalence of twin pregnancies was significantly higher in the PGD group. The cost of PGD was $7,956 U.S. per patient. Conclusions While PGD significantly prevented further miscarriages, there was no difference in the live birth rate. Couples should be fully informed of the similarity in the live birth rate, the similarity in time to become pregnancy, the advantages of PGD, such as the reduction in the miscarriage rate, as well as its disadvantages, such as the higher cost, and the advantages of a natural pregnancy, such as the avoidance of IVF failure. The findings presented here should be incorporated into the genetic counseling of patients with RPL and carrying a translocation. PMID:26083495

  8. Prevention of lysosomal storage diseases and derivation of mutant stem cell lines by preimplantation genetic diagnosis.

    PubMed

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

    2012-01-01

    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

  9. AB163. Microsatellite markers for preimplantation genetic diagnosis in Vietnamese DMD and hemophilia: a female carriers

    PubMed Central

    Tuan-Pham, Le Anh; Tran, Thinh Huy; Tran, Dat Quoc; Minh, Nguyen Thi; Huong, Nguyen Lien; Tien, Nguyen Viet; Ta, Van Thanh; Bui, The Hung; Tran, Van Khanh

    2015-01-01

    Microsatellite polymorphic markers were powerful tool to perform single cell diagnosis for preimplantation genetic diagnosis (PGD) in X-linked recessive disorders. This type of analysis requires haplotypes information of carrier mothers and affected sons. We present 12 Vietnamese families with duchenne muscular dystrophin (DMD) or Hemophilia A affected sons, six with each disorder. We established haplotypes based on linked microsatellite polymorphic markers in these families and performed diagnosis enabling embryo transfer from the PGD cycle. We also perform haplotypes analysis in five more families for each disease to identify more informative markers among other, in order to construct better strategy for future diagnosis. Microsatellite polymorphic markers flanking the F8 and DMD gene were used to identify haplotypes. Polar bodies (PB) were biopsied and analyzed to determine allelic association between the mutation and markers in multiplex PCR reaction. The results showed that 13 out of 28 embryos were found to be not affected by F8 or DMD gene inherited mutations and were available for transfer. Marker DXS9907, DSTR44, DSTR49 for DMD gene and marker FXS1073, DXS9897, DXS1073 for F8 gene were identified as the most frequent markers shown heterozygous alleles in mother carriers. PB analysis by microsatellite markers were proved to be useful technique for PGD of DMD and Hemophilia A families. Better strategy for PB diagnosis was built.

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

    PubMed

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

    2009-12-01

    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

  11. Clinical and Technical Overview of Preimplantation Genetic Diagnosis for Fragile X Syndrome: Experience at the University Hospital Virgen del Rocio in Spain

    PubMed Central

    Fernández, Raquel M.; Peciña, Ana; Lozano-Arana, Maria Dolores; Sánchez, Beatriz; García-Lozano, Juan Carlos; Borrego, Salud; Antiñolo, Guillermo

    2015-01-01

    Fragile X syndrome (FXS) accounts for about one-half of cases of X-linked intellectual disability and is the most common monogenic cause of mental impairment. Reproductive options for the FXS carriers include preimplantation genetic diagnosis (PGD). However, this strategy is considered by some centers as wasteful owing to the high prevalence of premature ovarian failure in FXS carriers and the difficulties in genetic diagnosis of the embryos. Here we present the results of our PGD Program applied to FXS, at the Department of Genetics, Reproduction and Fetal Medicine of the University Hospital Virgen del Rocío in Seville. A total of 11 couples have participated in our PGD Program for FXS since 2010. Overall, 15 cycles were performed, providing a total of 43 embryos. The overall percentage of transfers per cycle was 46.67% and the live birth rate per cycle was 13.33%. As expected, these percentages are considerably lower than the ones obtained in PGD for other pathologies. Our program resulted in the birth of 3 unaffected babies of FXS for 2 of the 11 couples (18.2%) supporting that, despite the important drawbacks of PGD for FXS, efforts should be devoted in offering this reproductive option to the affected families. PMID:26713318

  12. Preimplantation genetic diagnosis for gender selection in the United States

    SciTech Connect

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

    2009-08-20

    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.

  13. Experience of Preimplantation Genetic Diagnosis for Hemophilia at the University Hospital Virgen Del Rocío in Spain: Technical and Clinical Overview

    PubMed Central

    Fernández, Raquel M.; Peciña, Ana; Sánchez, Beatriz; Lozano-Arana, Maria Dolores; García-Lozano, Juan Carlos; Pérez-Garrido, Rosario; Núñez, Ramiro; Borrego, Salud; Antiñolo, Guillermo

    2015-01-01

    Hemophilia A and B are the most common hereditary hemorrhagic disorders, with an X-linked mode of inheritance. Reproductive options for the families affected with hemophilia, aiming at the prevention of the birth of children with severe coagulation disorders, include preimplantation genetic diagnosis (PGD). Here we present the results of our PGD Program applied to hemophilia, at the Department of Genetics, Reproduction and Fetal Medicine of the University Hospital Virgen del Rocío in Seville. A total of 34 couples have been included in our program since 2005 (30 for hemophilia A and 4 for hemophilia B). Overall, 60 cycles were performed, providing a total of 508 embryos. The overall percentage of transfers per cycle was 81.7% and the live birth rate per cycle ranged from 10.3 to 24.1% depending on the methodological approach applied. Although PGD for hemophilia can be focused on gender selection of female embryos, our results demonstrate that methodological approaches that allow the diagnosis of the hemophilia status of every embryo have notorious advantages. Our PGD Program resulted in the birth of 12 healthy babies for 10 out of the 34 couples (29.4%), constituting a relevant achievement for the Spanish Public Health System within the field of haematological disorders. PMID:26258137

  14. Healthy Baby Born to a Robertsonian Translocation Carrier following Next-Generation Sequencing-Based Preimplantation Genetic Diagnosis: A Case Report

    PubMed Central

    Lukaszuk, Krzysztof; Pukszta, Sebastian; Ochman, Karolina; Cybulska, Celina; Liss, Joanna; Pastuszek, Ewa; Zabielska, Judyta; Woclawek-Potocka, Izabela

    2015-01-01

    Preimplantation genetic diagnosis (PGD) is well established method for treatment of genetic problems associated with infertility. Moreover, PGD with next-generation sequencing (NGS) provide new possibilities for diagnosis and new parameters for evaluation in, for example, aneuploidy screening. The aim of the study was to report the successful pregnancy outcome following PGD with NGS as the method for 24 chromosome aneuploidy screening in the case of Robertsonian translocation. Day 3 embryos screening for chromosomal aneuploidy was performed in two consecutive in vitro fertilization (IVF) cycles, first with fluorescent in situ hybridization (FISH), and then with NGS-based protocol. In each IVF attempt, three embryos were biopsied. Short duration of procedures enabled fresh embryo transfer without the need for vitrification. First IVF cycle with the embryo selected using PGD analysis with the FISH method ended with pregnancy loss in week 8. The second attempt with NGS-based aneuploidy screening led to exclusion of the following two embryos: one embryo with 22 monosomy and one with multiple aneuploidies. The transfer of the only euploid blastocyst resulted in the successful pregnancy outcome. The identification of the euploid embryo based on the NGS application was the first successful clinical application of NGS-based PGD in the case of the Robertsonian translocation carrier couple. PMID:26495179

  15. Preimplantation Genetic Diagnosis: Prenatal Testing for Embryos Finally Achieving Its Potential

    PubMed Central

    Stern, Harvey J.

    2014-01-01

    Preimplantation genetic diagnosis was developed nearly a quarter-century ago as an alternative form of prenatal diagnosis that is carried out on embryos. Initially offered for diagnosis in couples at-risk for single gene genetic disorders, such as cystic fibrosis, spinal muscular atrophy and Huntington disease, preimplantation genetic diagnosis (PGD) has most frequently been employed in assisted reproduction for detection of chromosome aneuploidy from advancing maternal age or structural chromosome rearrangements. Major improvements have been seen in PGD analysis with movement away from older, less effective technologies, such as fluorescence in situ hybridization (FISH), to newer molecular tools, such as DNA microarrays and next generation sequencing. Improved results have also started to be seen with decreasing use of Day 3 blastomere biopsy in favor of polar body or Day 5 trophectoderm biopsy. Discussions regarding the scientific, ethical, legal and social issues surrounding the use of sequence data from embryo biopsy have begun and must continue to avoid concern regarding eugenic or inappropriate use of this technology. PMID:26237262

  16. The European Court legitimates access of Italian couples to assisted reproductive techniques and to pre-implantation genetic diagnosis.

    PubMed

    Turillazzi, Emanuela; Frati, Paola; Busardò, Francesco Paolo; Gulino, Matteo; Fineschi, Vittorio

    2015-07-01

    On 28 August 2012, the European Court of Human Rights (ECHR) issued a judgment regarding the requirements for the legitimate access of couples to assisted reproductive techniques (ART) and to pre-implantation genetic diagnosis (PGD). This judgment concerns the case of an Italian couple who found out after their first child was born with cystic fibrosis that they were healthy carriers of the disease. When the woman became pregnant again in 2010 and underwent fetal screening, it was found that the unborn child also had cystic fibrosis, whereupon she had the pregnancy terminated on medical grounds. In order to have the embryo genetically screened prior to implantation under the procedure of PGD, the couple sought to use in vitro fertilisation to have another child. Since article 1 of the Italian law strictly limits access to ART to sterile/infertile couples or those in which the man has a sexually transmissible disease, the couple appealed to the European court, raising the question of the violation of articles 8 and 14 of the European Convention on Human Rights. The applicants lodged a complaint that they were not allowed legitimate access to ART and to PGD to select an embryo not affected by the disease. The European Court affirmed that the prohibition imposed by Italian law violated article 8 of the European Convention on Human Rights. Focusing on important regulatory and legal differences among EU Nations in providing ART treatments and PGD, we derived some important similarities and differences. PMID:24777348

  17. Preimplantation diagnosis of genetic diseases.

    PubMed

    Adiga, S K; Kalthur, G; Kumar, P; Girisha, K M

    2010-01-01

    One of the landmarks in clinical genetics is prenatal diagnosis of genetic disorders. The recent advances in the field have made it possible to diagnose the genetic conditions in the embryos before implantation in a setting of in vitro fertilization. Polymerase chain reaction and fluorescence in situ hybridization are the two common techniques employed on a single or two cells obtained via embryo biopsy. The couple who seek in vitro fertilization may screen their embryos for aneuploidy and the couple at risk for a monogenic disorder but averse to abortion of the affected fetuses after prenatal diagnosis, are likely to be the best candidates to undergo this procedure. This article reviews the technique, indications, benefits, and limitations of pre-implantation genetic testing in clinical practice. PMID:20935409

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

    PubMed

    Edwards, R G

    2004-08-01

    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

  19. Preimplantation genetic diagnosis for a known cryptic translocation: follow-up clinical report and implication of segregation products.

    PubMed

    McKenzie, L J; Cisneros, P L; Torsky, S; Bacino, C A; Buster, J E; Carson, S A; Simpson, J L; Bischoff, F

    2003-08-15

    This report describes preimplantation genetic diagnosis (PGD) of a couple with a known paternally-derived balanced cryptic translocation 46,XY.ish t(2q;17q)(210E14-,B37c1+;B37c1-,210E14+) in embryos from a couple who previously had a child with severe mental retardation and was previously described in this journal [Bacino et al., 2000]. This child inherited the unbalanced product of translocation from her father: 46,XX.ish der(2)t(2q;17q)pat(210E14-,B37c1+). The couple desired a normal offspring and sought PGD to avoid clinical pregnancy termination. They were treated three times with in vitro fertilization followed by PGD. Two sequential FISH hybridizations were performed. In the first hybridization, telomeric probes to 2q and 17q and a chromosome 17 centromere probe were employed. The second hybridization screened for maternal age-related aneuploidy (X,Y,13,18,21). Of the 18 informative embryos, only 4 (22%) were normal. The remaining 12 (67%) were abnormal; most with unbalanced products (10/12) from the paternally-derived rearrangement. The most frequent mode of segregation observed for this cryptic translocation was adjacent-1 (7/18, 39%). This suggests cryptic translocations are amenable to PGD and, as are traditional translocations, demonstrate higher frequencies of unbalanced segregants than the empiric risk of 10-15% observed at amniocentesis or chorionic villus sampling. Thus, cryptic translocations presumably behave like overt translocations, in that PGD must be performed on a relatively large number of embryos to assure even 2-3 transferable embryos. PMID:12900903

  20. Number of embryos biopsied as a predictive indicator for the outcome of preimplantation genetic diagnosis by fluorescence in situ hybridisation in translocation cases.

    PubMed

    Tulay, P; Gultomruk, M; Findikli, N; Bahceci, M

    2016-02-01

    This study aimed to investigate the optimum number of embryos to be biopsied in order to increase the likelihood of obtaining a balanced/normal embryo following preimplantation genetic diagnosis (PGD) by fluorescence in situ hybridisation (FISH) for translocation carriers. Patients with low number of fertilised oocytes (?5) or low number of embryos available for PGD (<7) underwent multiple hormonal stimulation cycles and their embryos from each cycle were vitrified and accumulated to obtain at least three embryos for PGD. Fifty-seven PGD cycles were performed for translocation carriers by FISH on day 3 of embryo development. PGD and pregnancy outcomes were examined according to the number of embryos biopsied. The cancellation rates of embryo transfer for the reciprocal translocation carriers were 40% when more than eight embryos were biopsied and it was as high as 78% when low number of embryos (less than nine) were biopsied. For Robertsonian translocation carriers, when more than eight embryos were biopsied, there were no embryo transfer cancellations. This study showed that when there are more than nine embryos biopsied for PGD, the likelihood of obtaining a balanced embryo and positive pregnancy outcome is significantly higher (P < 0.05) in such the overall pregnancy rate was 63% for reciprocal and 86% for Robertsonian carriers. This was reduced to only 7% for reciprocal and 14% for Robertsonian translocation carriers when less than nine embryos were biopsied. One of the limitations of this study was that the analysis was performed by FISH and more studies should investigate the outcomes of embryo accumulation following comprehensive chromosome analysis. PMID:25601127

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

    PubMed Central

    Ehrich, Kathryn; Williams, Clare; Farsides, Bobbie

    2008-01-01

    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

  2. Sickle Cell Anemia Diagnosis, Treatment, & Genetics

    E-print Network

    Brutlag, Doug

    Sickle Cell Anemia Diagnosis, Treatment, & Genetics Katarzyna Zabrocka BIOC118Q #12;Sickle Cell and Citrate Agar Electrophoresis- hemoglobin will migrate in specific patterns. Sickle Cell Anemia is only one%20cell %20anemia&rid=gnd.section.98 http://en.wikipedia.org/wiki/Sickle-cell_disease http

  3. Clinical Considerations of Preimplantation Genetic Diagnosis for Monogenic Diseases

    PubMed Central

    Hu, Xiaokun; Wang, Jing; Li, Yubin; Wang, Yizi; Ding, Chenhui; Zeng, Yanhong; Xu, Yanwen; Zhou, Canquan

    2015-01-01

    Purpose The aim of this study was to explore factors contribute to the success of PGD cycles for monogenic diseases. Methods During a 3-year period (January 2009 to December 2012), 184 consecutive ICSI-PGD cycles for monogenic diseases reaching the ovum pick-up and fresh embryo-transfer stage performed at the Reproductive Medicine Center of The First Affiliated Hospital Of Sun Yat-sen University were evaluated. Results ICSI was performed on 2206 metaphase II oocytes, and normal fertilization and cleavage rates were 83.4% (1840/2206) and 96.2% (1770/1840), respectively. In the present study, 60.5% (181/299) of day 3 good-quality embryos developed into good-quality embryos on day 4 after biopsy. Collectively, 42.9% clinical pregnancy rate (79/184) and 28.5% implantation rate (111/389) were presented. In the adjusted linear regression model, the only two significant factors affecting the number of genetically unaffected embryos were the number of biopsied embryos (coefficient: 0.390, 95%CI 0.317–0.463, P = 0.000) and basal FSH level (coefficient: 0.198, 95%CI 0.031–0.365, P = 0.021). In the adjusted binary logistic regression model, the only two significant factors affecting pregnancy outcome were the number of genetically available transferable embryos after PGD (adjusted OR 1.345, 95% CI 1.148–1.575, P = 0.000) and number of oocyte retrieved (adjusted OR 0.934, 95% CI 0.877–0.994, P = 0.031). Conclusion There should be at least four biopsied embryos to obtain at least one unaffected embryos in a PGD system for patients with single gene disorder and under the condition of basal FSH level smaller than 8.0mmol/L. Moreover, if only a low number (< 4) of biopsied embryos are available on day 3, the chance of unaffected embryos for transfer was small, with poor outcome. PMID:26421428

  4. Preimplantation genetic diagnosis for elective sex selection, the IVF market economy, and the child--another long day's journey into night?

    PubMed

    Sills, E Scott; Palermo, Gianpiero D

    2002-09-01

    The promise of medical innovation has long evoked social commentary, particularly when personal reproductive autonomy may be involved. Development of the oral contraceptive, effective and safe surgical sterilization, and later IVF and ICSI are among the revolutionary developments where the initial reactions were dubious but were accorded mainstream status with sufficient clinical experience. In each instance, debate about the moral and social implications of these treatments accompanied their introduction into the medical marketplace. This pattern appears to be repeating itself in connection with the use of preimplantation genetic diagnosis (PGD) for elective sex selection of human embryos. As with prior challenges in reproductive medicine, the development of meaningful "guidelines" for this latest controversy has proven to be a contentious task. Indeed, the progression of ethics committee reports from the American Society for Reproductive Medicine seems to echo the ambivalence within society at large regarding this issue. In this report, we chronicle sex selection claims based on sperm sorting, and describe how flow cytometry and especially PGD have facilitated this selection at the gamete and embryo stage, respectively. In doing so, we also explore market forces and practitioner considerations associated with the application of PGD for this; related ethical issues with particular emphasis on the progeny derived from such treatment are also reviewed. PMID:12408539

  5. Preimplantation genetic diagnosis and the 'new' eugenics.

    PubMed Central

    King, D S

    1999-01-01

    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 and eugenic attitudes held by clinical geneticists in most countries, it results in eugenic outcomes even though no state coercion is involved. I argue that technological advances may soon make PID widely accessible. Because abortion is not involved, and multiple embryos are available, PID is radically more effective as a tool of genetic selection. It will also make possible selection on the basis of non-pathological characteristics, leading, potentially, to a full-blown free-market eugenics. For these reasons, I argue that PID should be strictly regulated. PMID:10226925

  6. Pheochromocytoma and Paraganglioma: Genetics, Diagnosis, and Treatment.

    PubMed

    Fishbein, Lauren

    2016-02-01

    Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare but unique neuroendocrine tumors. The hypersecretion of catecholamines from the tumors can be associated with high morbidity and mortality, even when tumors are benign. Up to 40% of PCCs/PGLs are associated with germline mutations in susceptibility genes. About one-quarter are malignant, defined by the presence of distant metastases. Treatment options for unresectable metastatic disease, including chemotherapy, (131)I-MIBG, and radiation, can offer limited tumor and hormone control, although none are curative. This article reviews the inherited genetics, diagnosis, and treatment of PCCs and PGLs. PMID:26614373

  7. Preimplantation diagnosis after assisted reproduction techniques for genetically-determined male infertility.

    PubMed

    Gianaroli, L; Magli, M C; Ferraretti, A P; Iammarrone, E

    2000-11-01

    One hundred and thirty-six cycles with a poor prognosis for full-term pregnancy underwent preimplantation genetic diagnosis (PGD) of aneuploidy. The mean maternal age was 31.8 +/- 2.5 years. Only patients younger than 36 years were included in the study with the aim of evaluating whether sperm indices have an effect on the chromosomal constitution of preimplantation embryos. No differences were detected in the percentage of aneuploid embryos; however a higher incidence of monosomies and trisomies was found in MESA-TESE embryos compared to the group of normospermic patients. In addition, an increase in the proportion of gonosomal aneuploidy seemed to be associated with the severity of the male factor parameters. The rate of de-novo chromosomal abnormalities in embryos from patients with a normal karyotype suggested an increased frequency proportional to the severity of the male factor condition, the proportion of monosomic and trisomic embryos, and the percentage of gonosomal aneuploidy increased accordingly. In the case of couples with a male altered karyotype, comparable frequency of chromosomally abnormal embryos, and monosomy and trisomy were observed irrespective of semen indices, gonosomal aneuploidy was only observed in one case where the patient had a karyotype with gonosomal mosaicism. These data confirm that the severe male infertility condition determines an increase in the rate of de-novo abnormalities, as anticipate by the follow-up of the children born after ICSI. PMID:11097437

  8. SICKLE CELL ANEMIA Genetics, Symptoms, Diagnosis, and Treatments

    E-print Network

    Brutlag, Doug

    SICKLE CELL ANEMIA Genetics, Symptoms, Diagnosis, and Treatments Iris Jovel Biochemistry 118Q #12;THE DISEASE: SICKLE CELL ANEMIA (SCA) Most common inherited blood, sickle shape #12;IMPLICATIONS OF SICKLE CELL ANEMIA Misshapen and rigid RBC fail

  9. Use of Contemporary Genetics in Cardiovascular Diagnosis

    PubMed Central

    George, Alfred L.

    2015-01-01

    An explosion of knowledge regarding the genetic and genomic basis for rare and common diseases has provided a framework for revolutionizing the practice of medicine. Achieving the reality of a genomic medicine era requires that basic discoveries are effectively translated into clinical practice through implementation of genetic and genomic testing. Clinical genetic tests have become routine for many inherited disorders and can be regarded as the standard-of-care in many circumstances including disorders affecting the cardiovascular system. New, high-throughput methods for determining the DNA sequence of all coding exons or complete genomes are being adopted for clinical use to expand the speed and breadth of genetic testing. Along with these extraordinary advances have emerged new challenges to practicing physicians for understanding when and how to use genetic testing along with how to appropriately interpret test results. This review will acquaint readers with general principles of genetic testing including newer technologies, test interpretation and pitfalls. The focus will be on testing genes responsible for monogenic disorders and on other emerging applications such as pharmacogenomic profiling. The discussion will be extended to the new paradigm of direct-to-consumer genetic testing and the value of assessing genomic risk for common diseases. PMID:25421045

  10. Pheochromocytoma and Paraganglioma: Diagnosis, Genetics, and Treatment.

    PubMed

    Kiernan, Colleen M; Solórzano, Carmen C

    2016-01-01

    This article highlights the epidemiology and pathophysiology of pheochromocytomas and paragangliomas. The current management of pheochromocytoma and paragangliomas, including utilization and interpretation of biochemical testing, preoperative imaging, and genetic screening are discussed. Furthermore, perioperative surgical management, outcomes, and recommended follow-up are reviewed. PMID:26610778

  11. Genetic skeletal dysplasias: A guide to diagnosis and management.

    PubMed

    Sewell, Mathew David; Chahal, Amanjot; Al-Hadithy, Nawfal; Blunn, Gordon W; Molloy, Sean; Hashemi-Nejad, Aresh

    2015-06-17

    The skeletal dysplasias are a large, heterogeneous group of genetic disorders characterised by abnormal growth, development and remodelling of the bones and cartilage that comprise the human skeleton. They typically present with disproportionate short stature in childhood, or premature osteoarthritis in adulthood. The latest classification lists 456 disorders under 40 group headings differentiated by specific clinical, radiographic and molecular criteria. Establishing an accurate diagnosis is important to predict final height, expected complications and treatment, and for specific genetic and psychological counselling. In addition to the skeletal disorder, individuals frequently demonstrate abnormalities of hearing, vision, neurological, pulmonary, renal or cardiac function that require multidisciplinary assessment. This review provides a guide to diagnosis and discusses management principles for the common limb and spinal abnormalities that affect quality of life for the majority. PMID:25391330

  12. [Genetic diagnosis and molecular pathology of inherited neuropathy].

    PubMed

    Takashima, Hiroshi

    2012-01-01

    Recent advances in genetic analysis technology have enabled a surprising progress in genetic diagnosis in the field of neurological disease research. High-throughput molecular biology techniques, such as microarrays and next-generation sequencing, are the major contributors to this progress and to new discoveries. Charcot-Marie-Tooth disease (CMT), a known hereditary motor and sensory neuropathy, is clinically and genetically heterogeneous. Genetic studies have revealed at least 35 disease causing-genes responsible for Charcot-Marie-Tooth disease. Genetic studies have revealed that abnormalities in the following factors are the cause of inherited neuropathies: myelin components, transcription factors controlling myelination, myelin maintenance system, differentiation factors related to the peripheral nerve, neurofilaments, protein transfer system, mitochondrial proteins, DNA repair, RNA/protein synthesis, ion channels, and aminoacyl-tRNA synthetase. On the other hand concomitant with the increase in the number of genes that must be screened for mutations, the labor and reagent costs for molecular genetic testing have increased significantly. Therefore, new methodology for detecting gene mutations is required. Based on the recent progress in DNA analysis methods, resequencing microarray appears to be an economical and highly sensitive method for detecting mutations. We have been screening CMT patients for mutations using originally designed microarray DNA chips since 2007, thencehaving identified disease causing mutations in MPZ, GJB1, PMP22, EGR2, MFN2, NEFL, PRX, AARS, GARS, DNM2, and SETX genes in CMT patients. PMID:22790800

  13. Genetic imprecision: Diagnosis of possible defects often cannot predict prognosis

    SciTech Connect

    Lewis, R.

    1991-05-01

    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.

  14. The first family with Tay-Sachs disease in Cyprus: Genetic analysis reveals a nonsense (c.78G>A) and a silent (c.1305C>T) mutation and allows preimplantation genetic diagnosis.

    PubMed

    Georgiou, Theodoros; Christopoulos, George; Anastasiadou, Violetta; Hadjiloizou, Stavros; Cregeen, David; Jackson, Marie; Mavrikiou, Gavriella; Kleanthous, Marina; Drousiotou, Anthi

    2014-12-01

    Tay-Sachs disease (TSD) is a recessively inherited neurodegenerative disorder caused by mutations in the HEXA gene resulting in ?-hexosaminidase A (HEX A) deficiency and neuronal accumulation of GM2 ganglioside. We describe the first patient with Tay-Sachs disease in the Cypriot population, a juvenile case which presented with developmental regression at the age of five. The diagnosis was confirmed by measurement of HEXA activity in plasma, peripheral leucocytes and fibroblasts. Sequencing the HEXA gene resulted in the identification of two previously described mutations: the nonsense mutation c.78G>A (p.Trp26X) and the silent mutation c.1305C>T (p.=). The silent mutation was reported once before in a juvenile TSD patient of West Indian origin with an unusually mild phenotype. The presence of this mutation in another juvenile TSD patient provides further evidence that it is a disease-causing mutation. Successful preimplantation genetic diagnosis (PGD) and prenatal follow-up were provided to the couple. PMID:25606403

  15. The first family with Tay-Sachs disease in Cyprus: Genetic analysis reveals a nonsense (c.78G>A) and a silent (c.1305C>T) mutation and allows preimplantation genetic diagnosis

    PubMed Central

    Georgiou, Theodoros; Christopoulos, George; Anastasiadou, Violetta; Hadjiloizou, Stavros; Cregeen, David; Jackson, Marie; Mavrikiou, Gavriella; Kleanthous, Marina; Drousiotou, Anthi

    2014-01-01

    Tay-Sachs disease (TSD) is a recessively inherited neurodegenerative disorder caused by mutations in the HEXA gene resulting in ?-hexosaminidase A (HEX A) deficiency and neuronal accumulation of GM2 ganglioside. We describe the first patient with Tay-Sachs disease in the Cypriot population, a juvenile case which presented with developmental regression at the age of five. The diagnosis was confirmed by measurement of HEXA activity in plasma, peripheral leucocytes and fibroblasts. Sequencing the HEXA gene resulted in the identification of two previously described mutations: the nonsense mutation c.78G>A (p.Trp26X) and the silent mutation c.1305C>T (p.=). The silent mutation was reported once before in a juvenile TSD patient of West Indian origin with an unusually mild phenotype. The presence of this mutation in another juvenile TSD patient provides further evidence that it is a disease-causing mutation. Successful preimplantation genetic diagnosis (PGD) and prenatal follow-up were provided to the couple. PMID:25606403

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

    SciTech Connect

    Boyce-Jacino, M.T.; Reynolds, J.; Nikiforov, T.

    1994-09-01

    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.

  17. Antenatal genetic diagnosis: current status and future prospects.

    PubMed

    Benzie, R J

    1979-03-17

    The current status of antenatal genetic diagnosis is reviewed and the limitations of present techniques are discussed. It is suggested that multidisciplinary clinics are the most efficient means of providing this aspect of health care. Advances in cell culture techniques, in ultrasonography and in fetoscopy will extend the services available, and the impact of this will be felt by the community. Education of the medical profession and the public in this area is necessary so that informed decision-making can take place. PMID:86383

  18. Genetic diagnosis of factor V Leiden using heteroduplex technology.

    PubMed

    Bowen, D J; Standen, G R; Granville, S; Bowley, S; Wood, N A; Bidwell, J

    1997-01-01

    A new genetic test has been developed for detection of the mutation known as factor V Leiden. The test employs heteroduplex technology and comprises a single PCR reaction followed immediately by PCR product analysis. It therefore represents the minimum practical route from blood/tissue sample to genetic result. A cohort of 100 patients with a history of thrombosis have been screened using both the new heteroduplex test and a previously described PCR-restriction endonuclease test. Results gave 100% correlation: normals 75 (75%), heterozygotes 24 (24%) and homozygotes 1 (1%). The heteroduplex test has been shown to give straightforward diagnosis in three different analytical systems: standard polyacrylamide gel electrophoresis (PAGE), mini-gel PAGE and capillary electrophoresis. The latter system is semiautomated, therefore rapid through-put of large sample numbers is now possible. PMID:9031460

  19. Genetics, diagnosis and management of colorectal cancer (Review)

    PubMed Central

    DE ROSA, MARINA; PACE, UGO; REGA, DANIELA; COSTABILE, VALERIA; DURATURO, FRANCESCA; IZZO, PAOLA; DELRIO, PAOLO

    2015-01-01

    Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. Surgery represents the mainstay of treatment in early cases but often patients are primarily diagnosed in an advanced stage of disease and sometimes also distant metastases are present. Neoadjuvant therapy is therefore needed but drug resistance may influence response and concur to recurrent disease. At molecular level, it is a very heterogeneous group of diseases with about 30% of hereditary or familial cases. During colorectal adenocarcinomas development, epithelial cells from gastrointestinal trait acquire sequential genetic and epigenetic mutations in specific oncogenes and/or tumour suppressor genes, causing CRC onset, progression and metastasis. Molecular characterization of cancer associated mutations gives valuable information about disease prognosis and response to the therapy. Very early diagnosis and personalized care, as well as a better knowledge of molecular basis of its onset and progression, are therefore crucial to obtain a cure of CRC. In this review, we describe updated genetics, current diagnosis and management of CRC pointing out the extreme need for a multidisciplinary approach to achieve the best results in patient outcomes. PMID:26151224

  20. Progress in understanding the diagnosis and molecular genetics of macrothrombocytopenias.

    PubMed

    Favier, Remi; Raslova, Hana

    2015-09-01

    The inherited macrothrombocytopenias constitute a subgroup of congenital platelet disorders that is the best characterized from the genetic point of view. This clinically heterogeneous subgroup is characterized by a variable degree of bleeding but without predisposition to haematological malignancies, as seen in the two other subgroups. The classification of inherited thrombocytopenia is traditionally based on the description of different clinical and biological features, in particular the measurement of the mean platelet volume. In certain disorders, biochemical platelet components are abnormal, and their analyses are useful in diagnosis. However, these approaches present several limitations, and many cases remain undiagnosed, especially for patients without a clear family history. An analysis of genetic abnormalities was subsequently used for classification, demonstrating that some different clinical entities were, in fact, identical. The genomic approach that was used initially to accurately link some phenotypic diagnoses with the causal genetic alteration was positional cloning and DNA sequencing. More recently, next generation sequencing in the form of whole-genome or -exome sequencing and RNA sequencing has been developed. This review will focus on the progress in understanding the different macrothrombocytopenias that have been identified. PMID:25944497

  1. Discussing options between patients and health care professionals in genetic diagnosis: ethical and legal criteria

    PubMed Central

    Nicolás, Pilar

    2007-01-01

    The specific characteristics of genetic data lead to ethical-legal conflicts in the framework of genetic diagnosis. Several international organisations, including UNESCO and the Council of Europe, have enacted rules referring to the use of genetic information. This paper discusses possible legal and ethical criteria that could be used in genetic testing. PMID:19725990

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

    PubMed Central

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

    2014-01-01

    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

  3. Parents’ experiences of receiving their child’s genetic diagnosis: A qualitative study to inform clinical genetics practice

    PubMed Central

    Ashtiani, Setareh; Makela, Nancy; Carrion, Prescilla; Austin, Jehannine

    2014-01-01

    Purpose Little is currently known about how parents experience the medical genetics appointment at which their child receives a genetic diagnosis. Methods We conducted semi-structured in-person interviews with 13 parents of 10 index children to explore their experience in the medical genetics appointment in which they received their child’s genetic diagnosis. Guided by grounded theory, we used a constant comparative approach to data analysis, and the transcribed interviews were coded and sorted, and thematic categories identified. Results 61.5% of parents experienced the diagnosis session as negative, 23% felt the experience was positive, and 15.5% were ambivalent. Receiving emotional support, an outline of the follow-up plans, and messages of hope and perspective during the session seemed to positively influence parents’ experience, while feeling that their role was as a passive receiver of information and using difficult medical terminology negatively influenced parents’ overall experience. Parental preparedness for the information, and the parents’ emotional reaction to the diagnosis were also factors that influenced the parental experience. Few participants understood the role of the genetic counselor. Conclusion Our results provide in-depth insight into the parental experience of the pediatric medical genetics diagnosis session. We propose a mechanism through which parental experience shapes their perception of the medical genetics session. PMID:24706543

  4. Genetic testing and counseling in the diagnosis and management of young-onset dementias.

    PubMed

    Goldman, Jill S

    2015-06-01

    Young-onset dementia is hereditary, multifactorial, or sporadic. The most common hereditary dementias include Alzheimer disease, frontotemporal degeneration, Huntington disease, prion diseases, and cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Careful attainment of family history assists with diagnosis and determining the likelihood of a genetic cause, and can direct genetic testing. The type of genetic testing depends on confidence of the diagnosis, patient's and affected relatives' symptoms, and the number of disease genes. Single gene, disease-specific gene panels, and large dementia panels are available. Genetic counseling should be given and informed consent obtained. Predictive testing follows the Huntington disease protocol. PMID:25998117

  5. Support vector machine-based image classification for genetic syndrome diagnosis

    E-print Network

    Lerner, Boaz

    it allows detection of numerical chromosome abnormalities during nor- mal cell interphase. An important-based image classifiers, thereby enabling the diagnosis of genetic abnormalities. By thresholding the distance chromosomes. FISH offers numerous advantages compared with conventional cyto- genetic techniques since

  6. A case report of Fanconi anemia diagnosed by genetic testing followed by prenatal diagnosis.

    PubMed

    Lee, Hwa Jeen; Park, Seungman; Kang, Hyoung Jin; Jun, Jong Kwan; Lee, Jung Ae; Lee, Dong Soon; Park, Sung Sup; Seong, Moon-Woo

    2012-09-01

    Fanconi anemia (FA) is a rare genetic disorder affecting multiple body systems. Genetic testing, including prenatal testing, is a prerequisite for the diagnosis of many clinical conditions. However, genetic testing is complicated for FA because there are often many genes that are associated with its development, and large deletions, duplications, or sequence variations are frequently found in some of these genes. This study describes successful genetic testing for molecular diagnosis, and subsequent prenatal diagnosis, of FA in a patient and his family in Korea. We analyzed all exons and flanking regions of the FANCA, FANCC, and FANCG genes for mutation identification and subsequent prenatal diagnosis. Multiplex ligation-dependent probe amplification analysis was performed to detect large deletions or duplications in the FANCA gene. Molecular analysis revealed two mutations in the FANCA gene: a frameshift mutation c.2546delC and a novel splice-site mutation c.3627-1G>A. The FANCA mutations were separately inherited from each parent, c.2546delC was derived from the father, whereas c.3627-1G>A originated from the mother. The amniotic fluid cells were c.3627-1G>A heterozygotes, suggesting that the fetus was unaffected. This is the first report of genetic testing that was successfully applied to molecular diagnosis of a patient and subsequent prenatal diagnosis of FA in a family in Korea. PMID:22950077

  7. Molecular diagnosis of some common genetic diseases in Russia and the former USSR: present and future.

    PubMed Central

    Baranov, V S

    1993-01-01

    The current state of molecular diagnosis of some common genetic diseases, including cystic fibrosis, Duchenne muscular dystrophy, haemophilia A and B, phenylketonuria, and thalassaemia, in Russia and elsewhere in the former USSR is reviewed. Data on carrier detection and prenatal diagnosis are presented and some objective problems and obstacles hampering efficient molecular diagnosis in Russia are discussed. The necessity for molecular diagnosis of some other inherited diseases (for example, von Willebrand's disease, Martin-Bell syndrome, polycystic kidney disease, Huntington's disease, and myotonic dystrophy) is stressed. The need for establishing new diagnostic centres dealing with the most common diseases, as well as rare genetic diseases, is substantiated. Perspectives on the implementation of new molecular methods and new technical approaches (preimplantation embryo diagnosis, fetal cells selected from maternal blood) are briefly outlined. PMID:8445619

  8. Molecular diagnosis and genetic counseling for fragile X mental retardation.

    PubMed

    Pandey, U B; Phadke, S R; Mittal, B

    2004-03-01

    The fragile X syndrome is the most frequent cause of inherited mental retardation. It is caused by a dynamic mutation: the progressive expansion of polymorphic (CGG)n trinucleotide repeats located in the promoter region of the FMRI gene at Xq27.3. The cloning of the FMRI gene and the elucidation of the molecular basis of the fragile X syndrome is of great importance for the diagnosis and understanding of this unusual type of mutation. Although extensively studied, the mechanism behind the transition from stable normal (CGG)n alleles to the carrier state (an unstable premutation) and from premutation to mutation is partially understood. The clinical diagnosis of fragile X mental retardation (FXMR) is not possible as dysmorphic features are subtle. Molecular diagnosis by Southern Blot is the confirmatory test that makes carrier detection and prenatal diagnosis possible. As the risk of recurrence of FXMR is high in the family and carrier relatives, an identification of fragile X positive children, and offering carrier detection and prenatal diagnosis to the families is very important. It is possible by screening mentally retarded children and adults even if there is no family history of mental retardation or typical behavioral or physical features associated with the fragile X phenotype. In this review we have discussed the method for the diagnosis and counseling of the families. The complexities due to premutation and the variable severity of manifestations in carrier females need to be understood while counseling fragile X families. PMID:15069237

  9. Clinical Application of Antenatal Genetic Diagnosis of Osteogenesis Imperfecta Type IV

    PubMed Central

    Yuan, Jing; Li, Song; Xu, YeYe; Cong, Lin

    2015-01-01

    Background Clinical analysis and genetic testing of a family with osteogenesis imperfecta type IV were conducted, aiming to discuss antenatal genetic diagnosis of osteogenesis imperfecta type IV. Material/Methods Preliminary genotyping was performed based on clinical characteristics of the family members and then high-throughput sequencing was applied to rapidly and accurately detect the changes in candidate genes. Results Genetic testing of the III5 fetus and other family members revealed missense mutation in c.2746G>A, pGly916Arg in COL1A2 gene coding region and missense and synonymous mutation in COL1A1 gene coding region. Conclusions Application of antenatal genetic diagnosis provides fast and accurate genetic counseling and eugenics suggestions for patients with osteogenesis imperfecta type IV and their families. PMID:25835785

  10. Preimplantation Genetic Testing in the 21st Century: Uncharted Territory

    PubMed Central

    Brezina, Paul R.

    2013-01-01

    The past hundred years have given birth to arguably the most profound changes in society, medicine, and technology the world has ever witnessed. Genetics is one such field that has enjoyed a meteoric rise during this time. Progressing from Mendelian genetics to the discovery of DNA to the ability to sequence the human genome, perhaps no other discipline holds more promise to affect future change than genetics. Technology currently exists to evaluate some of the genetic information held by developing embryos in the context of an in vitro fertilization (IVF) cycle. This information is then used to determine which embryos are selected for uterine transfer. Many societies have enacted legislation to protect against possible abuses utilizing this technology. However, it is incumbent upon society to continue ensuring that preimplantation genetic diagnosis (PGD)—and genetic testing in general—is applied in a way that utilizes its potential in a responsible manner to improve health care. PMID:24453515

  11. Usher syndrome: an effective sequencing approach to establish a genetic and clinical diagnosis.

    PubMed

    Lenarduzzi, S; Vozzi, D; Morgan, A; Rubinato, E; D'Eustacchio, A; Osland, T M; Rossi, C; Graziano, C; Castorina, P; Ambrosetti, U; Morgutti, M; Girotto, G

    2015-02-01

    Usher syndrome is an autosomal recessive disorder characterized by retinitis pigmentosa, sensorineural hearing loss and, in some cases, vestibular dysfunction. The disorder is clinically and genetically heterogeneous and, to date, mutations in 11 genes have been described. This finding makes difficult to get a precise molecular diagnosis and offer patients accurate genetic counselling. To overcome this problem and to increase our knowledge of the molecular basis of Usher syndrome, we designed a targeted resequencing custom panel. In a first validation step a series of 16 Italian patients with known molecular diagnosis were analysed and 31 out of 32 alleles were detected (97% of accuracy). After this step, 31 patients without a molecular diagnosis were enrolled in the study. Three out of them with an uncertain Usher diagnosis were excluded. One causative allele was detected in 24 out 28 patients (86%) while the presence of both causative alleles characterized 19 patients out 28 (68%). Sixteen novel and 27 known alleles were found in the following genes: USH2A (50%), MYO7A (7%), CDH23 (11%), PCDH15 (7%) and USH1G (2%). Overall, on the 44 patients the protocol was able to characterize 74 alleles out of 88 (84%). These results suggest that our panel is an effective approach for the genetic diagnosis of Usher syndrome leading to: 1) an accurate molecular diagnosis, 2) better genetic counselling, 3) more precise molecular epidemiology data fundamental for future interventional plans. PMID:25575603

  12. Niacin and biosynthesis of PGD2 by platelet COX-1 in mice and humans

    PubMed Central

    Song, Wen-Liang; Stubbe, Jane; Ricciotti, Emanuela; Alamuddin, Naji; Ibrahim, Salam; Crichton, Irene; Prempeh, Maxwell; Lawson, John A.; Wilensky, Robert L.; Rasmussen, Lars Melholt; Puré, Ellen; FitzGerald, Garret A.

    2012-01-01

    The clinical use of niacin to treat dyslipidemic conditions is limited by noxious side effects, most commonly facial flushing. In mice, niacin-induced flushing results from COX-1–dependent formation of PGD2 and PGE2 followed by COX-2–dependent production of PGE2. Consistent with this, niacin-induced flushing in humans is attenuated when niacin is combined with an antagonist of the PGD2 receptor DP1. NSAID-mediated suppression of COX-2–derived PGI2 has negative cardiovascular consequences, yet little is known about the cardiovascular biology of PGD2. Here, we show that PGD2 biosynthesis is augmented during platelet activation in humans and, although vascular expression of DP1 is conserved between humans and mice, platelet DP1 is not present in mice. Despite this, DP1 deletion in mice augmented aneurysm formation and the hypertensive response to Ang II and accelerated atherogenesis and thrombogenesis. Furthermore, COX inhibitors in humans, as well as platelet depletion, COX-1 knockdown, and COX-2 deletion in mice, revealed that niacin evoked platelet COX-1–derived PGD2 biosynthesis. Finally, ADP-induced spreading on fibrinogen was augmented by niacin in washed human platelets, coincident with increased thromboxane (Tx) formation. However, in platelet-rich plasma, where formation of both Tx and PGD2 was increased, spreading was not as pronounced and was inhibited by DP1 activation. Thus, PGD2, like PGI2, may function as a homeostatic response to thrombogenic and hypertensive stimuli and may have particular relevance as a constraint on platelets during niacin therapy. PMID:22406532

  13. Professional phagocytic granulocyte-derived PGD2 regulates the resolution of inflammation in fish.

    PubMed

    Gómez-Abellán, Victoria; Montero, Jana; López-Muñoz, Azucena; Figueras, Antonio; Arizcun, Marta; Mulero, Victoriano; Sepulcre, María P

    2015-10-01

    Prostaglandins (PGs) play a key role in the development on the immune response through the regulation of both pro- and anti-inflammatory processes. PGD(2) can be either pro- or anti-inflammatory depending on the inflammatory milieu. Prostaglandin D synthase (PGDS) is the enzyme responsible for the conversion of PGH(2) to PGD(2). In mammals, two types of PGDS synthase have been described, the hematopoietic (H-PGDS) and the lipocalin (L-PGDS). In the present study we describe the existence of two orthologs of the mammalian L-PGDS (PGDS1 and PGDS2) in the gilthead seabream and characterize their gene expression profiles and biological activity. The results showed a dramatic induction of the gene coding for PGDS1 in acidophilic granulocytes (AGs), which are functionally equivalent to mammalian neutrophils, after a prolonged in vitro activation with different pathogen associated molecular patterns (PAMPs). In contrast PGDS2 was not expressed in these cells. The functional relevance of the induction of PGDS1 in AGs was confirmed by the ability of these cells to release PGD(2) upon PAMP stimulation. To gain further insight into the role of PGD(2) in the resolution of inflammation in fish, we examined the ability of PGD(2) or its cyclopentenone derivates (cyPGs) to modulate the main functional activities of AGs. It was found that both PGD(2) and cyPGs inhibited the production of reactive oxygen species and downregulated the transcript levels of the gene encoding interleukin-1?. Taken together, these results demonstrate that the use of PGD(2) and its metabolites in the resolution of inflammation was established before the divergence of fish from tetrapods more than 450 million years ago and support a critical role for granulocytes in the resolution of inflammation in vertebrates. PMID:26027798

  14. Genetic algorithm and image processing for osteoporosis diagnosis.

    PubMed

    Jennane, R; Almhdie-Imjabber, A; Hambli, R; Ucan, O N; Benhamou, C L

    2010-01-01

    Osteoporosis is considered as a major public health threat. It is characterized by a decrease in the density of bone, decreasing its strength and leading to an increased risk of fracture. In this work, the morphological, topological and mechanical characteristics of 2 populations of arthritic and osteoporotic trabecular bone samples are evaluated using artificial intelligence and recently developed skeletonization algorithms. Results show that genetic algorithms associated with image processing tools can precisely separate the 2 populations. PMID:21096487

  15. Ethics of preimplantation diagnosis: recordings from the Fourth International Symposium on Preimplantation Genetics.

    PubMed

    Edwards, R G

    2003-03-01

    New ethical issues emerge from the rapid expansion in knowledge of preimplantation genetics. These were summarized and debated recently during the final session at the Fourth International Symposium on Preimplantation Genetics, held in Cyprus, 10-13 April 2002. Divergent views were expressed on various topics including unique issues in preimplantation genetic diagnosis, the sexing of embryos, cloning and other matters. Differing ethical viewpoints emerged, and alternative ways of coping with certain issues were described. This complex area of ethical and social issues will demand detailed counselling of patients, ongoing debate among professionals, and perhaps legislation or central regulatory authorities to decide on the detailed application of its new technologies. PMID:12675996

  16. Ethical challenges in assisted reproduction: the place of preimplantation genetic diagnosis in a just society.

    PubMed

    Whetstine, Leslie M

    2015-04-01

    The purpose of this article is to provide an overview of preimplantation genetic diagnosis and identify the relevant moral questions it raises. In the course of this discussion, the scope of parental rights and the inherent difficulty in defining disease/disability will be considered. PMID:24334349

  17. Automated Test Assembly for Cognitive Diagnosis Models Using a Genetic Algorithm

    ERIC Educational Resources Information Center

    Finkelman, Matthew; Kim, Wonsuk; Roussos, Louis A.

    2009-01-01

    Much recent psychometric literature has focused on cognitive diagnosis models (CDMs), a promising class of instruments used to measure the strengths and weaknesses of examinees. This article introduces a genetic algorithm to perform automated test assembly alongside CDMs. The algorithm is flexible in that it can be applied whether the goal is to…

  18. 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.DeMoor, Yves.Moreau}@esat.kuleuven.be, gbeligia@uwg.gr Abstract. Pancreatic cancer is one of the leading causes various cancer types. In this study we aim to facilitate early detection of the pancreatic cancer

  19. Small Ruminant Lentiviruses: Genetic Variability, Tropism and Diagnosis

    PubMed Central

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

    2013-01-01

    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

  20. Biochemical and genetic diagnosis of 21-hydroxylase deficiency.

    PubMed

    Falhammar, Henrik; Wedell, Anna; Nordenström, Anna

    2015-11-01

    Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is caused by mutations in the CYP21A2 gene and is often fatal in its classic forms if not treated with glucocorticoids. In contrast, non-classic CAH (NCCAH), with a prevalence from 0.1 % up to a few percentages in certain ethnic groups, only results in mild partial cortisol insufficiency and patients survive without treatment. Most NCCAH cases are never identified, but unnecessary suffering due to hyperandrogenism, especially in females, can be avoided by a correct diagnosis. A 17-hydroprogesterone (17OHP) level above 300 nmol/L indicates classic CAH while 30-300 nmol/L in adult males or females (follicular phase or if anovulatoric) indicates NCCAH. The gold standard for diagnosing NCCAH is the ACTH stimulation test. Deletion, large gene conversions, and nine microconversion-derived mutations are the most common CYP21A2 mutations. However, almost 200 rare mutations have been described. Since there is a good genotype-phenotype relationship, genotyping provides valuable diagnostic, as well as prognostic information. Neonatal screening for CAH is now performed in an increasing number of countries with the main goal of reducing mortality and morbidity due to salt-losing adrenal crises in the newborn period. In addition, screening may shorten the time to diagnosis in virilized girls. Neonatal screening misses some patients with milder classic CAH and most NCCAH cases. In conclusion, diagnosing classic CAH is life-saving, but diagnosing NCCAH is also important to prevent unnecessary suffering. PMID:26336836

  1. Clinical applications of schizophrenia genetics: genetic diagnosis, risk, and counseling in the molecular era

    PubMed Central

    Costain, Gregory; Bassett, Anne S

    2012-01-01

    Schizophrenia is a complex neuropsychiatric disease with documented clinical and genetic heterogeneity, and evidence for neurodevelopmental origins. Driven by new genetic technologies and advances in molecular medicine, there has recently been concrete progress in understanding some of the specific genetic causes of this serious psychiatric illness. In particular, several large rare structural variants have been convincingly associated with schizophrenia, in targeted studies over two decades with respect to 22q11.2 microdeletions, and more recently in large-scale, genome-wide case-control studies. These advances promise to help many families afflicted with this disease. In this review, we critically appraise recent developments in the field of schizophrenia genetics through the lens of immediate clinical applicability. Much work remains in translating the recent surge of genetic research discoveries into the clinic. The epidemiology and basic genetic parameters (such as penetrance and expression) of most genomic disorders associated with schizophrenia are not yet well characterized. To date, 22q11.2 deletion syndrome is the only established genetic subtype of schizophrenia of proven clinical relevance. We use this well-established association as a model to chart the pathway for translating emerging genetic discoveries into clinical practice. We also propose new directions for research involving general genetic risk prediction and counseling in schizophrenia. PMID:23144566

  2. A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies.

    PubMed

    Parikh, Sumit; Bernard, Geneviève; Leventer, Richard J; van der Knaap, Marjo S; van Hove, Johan; Pizzino, Amy; McNeill, Nathan H; Helman, Guy; Simons, Cas; Schmidt, Johanna L; Rizzo, William B; Patterson, Marc C; Taft, Ryan J; Vanderver, Adeline

    2015-04-01

    Leukodystrophies (LD) and genetic leukoencephalopathies (gLE) are disorders that result in white matter abnormalities in the central nervous system (CNS). Magnetic resonance (MR) imaging (MRI) has dramatically improved and systematized the diagnosis of LDs and gLEs, and in combination with specific clinical features, such as Addison's disease in Adrenoleukodystrophy or hypodontia in Pol-III related or 4H leukodystrophy, can often resolve a case with a minimum of testing. The diagnostic odyssey for the majority LD and gLE patients, however, remains extensive--many patients will wait nearly a decade for a definitive diagnosis and at least half will remain unresolved. The combination of MRI, careful clinical evaluation and next generation genetic sequencing holds promise for both expediting the diagnostic process and dramatically reducing the number of unresolved cases. Here we present a workflow detailing the Global Leukodystrophy Initiative (GLIA) consensus recommendations for an approach to clinical diagnosis, including salient clinical features suggesting a specific diagnosis, neuroimaging features and molecular genetic testing. We also discuss recommendations on the use of broad-spectrum next-generation sequencing in instances of ambiguous MRI or clinical findings. We conclude with a proposal for systematic trials of genome-wide agnostic testing as a first line diagnostic in LDs and gLEs given the increasing number of genes associated with these disorders. PMID:25655951

  3. [Diagnosis of MDS: morphology, chromosome abnormalities and genetic mutations].

    PubMed

    Hata, Tomoko

    2015-10-01

    Myelodysplastic syndromes (MDS) are a group of hematological neoplasms associated with ineffective hematopoiesis and that can transform into acute leukemia. The clinical classification of MDS which is defined by cytopenia, the rate of blasts in peripheral blood and bone marrow, dysplasia, and chromosomal abnormalities, has undergone continuous revision. To increase the accuracy of dysplastic evaluation, IWGM-MDS and the Research Committee for Idiopathic Hematopoietic Disorders, Ministry of Health, Labour and Welfare, Japan have proposed a quantitative and qualitative definition of dysplasia. Recently, refining the definition of dysgranulopoiesis was proposed by IWGM-MDS. Neutrophils with abnormal clumping of chromatin, and harboring more than 4 nuclear projections, were recognized as dysplastic features. At present, karyotypic abnormalities are detected in approximately 50% of de novo MDS and these remain the most critical prognostic factor. In the new cytogenetic scoring system, cytogenetic abnormalities were classified into five prognostic subgroups. This new classification was adopted by the revised IPSS. Approximately 80% to 90% of MDS patients have detectable mutations by whole-exon sequencing or whole genome sequencing. Many genetic mutations had biological and prognostic significance. It is important to further understand the utility of this factor in determining prognosis and in selecting among therapeutic options. PMID:26458436

  4. Next generation sequencing and the future of genetic diagnosis.

    PubMed

    Lohmann, Katja; Klein, Christine

    2014-10-01

    The introduction of next generation sequencing (NGS) has led to an exponential increase of elucidated genetic causes in both extremely rare diseases and common but heterogeneous disorders. It can be applied to the whole or to selected parts of the genome (genome or exome sequencing, gene panels). NGS is not only useful in large extended families with linkage information, but may also be applied to detect de novo mutations or mosaicism in sporadic patients without a prior hypothesis about the mutated gene. Currently, NGS is applied in both research and clinical settings, and there is a rapid transition of research findings to diagnostic applications. These developments may greatly help to minimize the "diagnostic odyssey" for patients as whole-genome analysis can be performed in a few days at reasonable costs compared with gene-by-gene analysis based on Sanger sequencing following diverse clinical tests. Despite the enthusiasm about NGS, one has to keep in mind its limitations, such as a coverage and accuracy of?

  5. Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. European Society of Human Genetics and European Society of Human Reproduction and Embryology.

    PubMed

    Harper, Joyce C; Geraedts, Joep; Borry, Pascal; Cornel, Martina C; Dondorp, Wybo; Gianaroli, Luca; Harton, Gary; Milachich, Tanya; Kääriäinen, Helena; Liebaers, Inge; Morris, Michael; Sequeiros, Jorge; Sermon, Karen; Shenfield, Françoise; Skirton, Heather; Soini, Sirpa; Spits, Claudia; Veiga, Anna; Vermeesch, Joris Robert; Viville, Stéphane; de Wert, Guido; Macek, Milan

    2013-11-01

    In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide an update of selected topics that have evolved since 2005. PMID:24225486

  6. Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy

    PubMed Central

    Harper, Joyce C; Geraedts, Joep; Borry, Pascal; Cornel, Martina C; Dondorp, Wybo; Gianaroli, Luca; Harton, Gary; Milachich, Tanya; Kääriäinen, Helena; Liebaers, Inge; Morris, Michael; Sequeiros, Jorge; Sermon, Karen; Shenfield, Françoise; Skirton, Heather; Soini, Sirpa; Spits, Claudia; Veiga, Anna; Vermeesch, Joris Robert; Viville, Stéphane; de Wert, Guido; Macek, Milan

    2013-01-01

    In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation – ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide an update of selected topics that have evolved since 2005. PMID:24225486

  7. Gene scene: Earlier, eventually more specific, prenatal genetic diagnosis in realm of possibility

    SciTech Connect

    Randall, T.

    1990-12-26

    A new genetic technique that can amplify the DNA of a single cell has flung open the window of opportunity for prenatal genetic diagnosis to just 3 days after conception, and even to the unfertilized egg. In vitro fertilization (IVF) specialists at the Institute of Obstetrics and Gynecology at London's Postgraduate medical School, Hammersmith Hospital have determined the sex of human embryos at the eight-cell stage of development from five couples at risk for X chromosome-linked diseases. The female embryos, which do not risk inheriting the disease, were then successfully implanted in the uterus and carried to full term.

  8. Next-generation sequencing and genetic diagnosis of Charcot-Marie-Tooth disease

    PubMed Central

    Verma, Ashok

    2014-01-01

    Over 70 different Charcot-Marie-Tooth disease (CMT)–associated genes have now been discovered and their number is growing. Conventional genetic testing for all CMT genes is cumbersome, expensive, and impractical in an individual patient. Next-generation sequencing (NGS) technology allows cost-effective sequencing of large scale DNA, even entire exome (coding sequences) or whole genome and thus, NGS platform can be employed to effectively target a large number or all CMT-related genes for accurate diagnosis. This overview discusses how NGS can be strategically used for genetic diagnosis in patients with CMT or unexplained neuropathy. A comment is made to combine simple clinical and electrophysiological algorithm to assign patients to major CMT subtypes and then employ NGS to screen for all known mutations in the subtype-specific CMT gene panel. PMID:25506157

  9. Early diagnosis of pyridoxine-dependent epilepsy: video-EEG monitoring and biochemical and genetic investigation.

    PubMed

    Ville, Dorothée; Ginguene, Carole; Marignier, Stéphanie; des Portes, Vincent; de Bellescize, Jullita

    2013-11-01

    Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive metabolic disease. A delay of treatment may affect outcome and early initiation of pyridoxine based on effective diagnosis is crucial to ensure good cognitive outcome in neonates. A consensus for the diagnosis of PDE is based on refractive seizures and responsiveness to pyridoxine, however, a growing body of evidence suggests that additional elements should be considered which include biochemical data, genetic screening, and EEG monitoring. We present a case study of a neonate with PDE, who presented with misleading clinical presentation and a novel mutation in the antiquitin (ALDH7A1) gene (A294V), and highlight important aspects in order to consider the definition of diagnosis and management of PDE in the light of more recent data. PMID:23916709

  10. The contribution of molecular genetics in the diagnosis and management of neuromuscular disorders.

    PubMed

    Kakulas, B A; Laing, N G; Johnsen, R D

    1999-01-01

    It is true that the recent advances in molecular genetics have generated a medical revolution. This is especially true for the inherited neuromuscular disorders. There have been many spectacular recent discoveries with new genes being found and their protein products identified. One of the most remarkable aspects of this progress is the nexus which has developed between the basic discovery and its clinical application. As soon as a new genetic mutation is reported, the information may be used immediately to establish the molecular diagnosis for that disorder in any part of the world which has a DNA laboratory. This is done by using primers derived from the published DNA sequences using the polymerase chain reaction (PCR). This development is of immense value for the clinician as it provides an exact molecular diagnosis often with prognostic information and the test results can be used for genetic counselling and prenatal diagnosis. One of the unexpected outcomes of this work has been the surprising variation which has been shown to exist between genotype and phenotype. Previously, one mutation was believed to be responsible for one clinical disorder. However, it is now known that one genotype may be responsible for a variety of phenotypes and vice versa. In the field of neuromuscular disorders the most notable advances have occurred for Duchenne muscular dystrophy and the related dystrophinopathies and for the group of limb girdle muscular dystrophies, especially the subgroup of sarcoglycanopathies. Other areas are the congenital myopathies, the 'channel-opathies' and the mitochondrial cytopathies. In this review the most commonly used molecular genetic and immunocytochemical methods using antibodies to the protein product are outlined together with the principles of their application in the neuromuscular clinic. Included are the provisos and pitfalls which need to be kept in mind in the interpretation of DNA results for each patient. PMID:10370969

  11. Improved inherited peripheral neuropathy genetic diagnosis by whole-exome sequencing

    PubMed Central

    Drew, Alexander P; Zhu, Danqing; Kidambi, Aditi; Ly, Carolyn; Tey, Shelisa; Brewer, Megan H; Ahmad-Annuar, Azlina; Nicholson, Garth A; Kennerson, Marina L

    2015-01-01

    Inherited peripheral neuropathies (IPNs) are a group of related diseases primarily affecting the peripheral motor and sensory neurons. They include the hereditary sensory neuropathies (HSN), hereditary motor neuropathies (HMN), and Charcot-Marie-Tooth disease (CMT). Using whole-exome sequencing (WES) to achieve a genetic diagnosis is particularly suited to IPNs, where over 80 genes are involved with weak genotype–phenotype correlations beyond the most common genes. We performed WES for 110 index patients with IPN where the genetic cause was undetermined after previous screening for mutations in common genes selected by phenotype and mode of inheritance. We identified 41 missense sequence variants in the known IPN genes in our cohort of 110 index patients. Nine variants (8%), identified in the genes MFN2, GJB1, BSCL2, and SETX, are previously reported mutations and considered to be pathogenic in these families. Twelve novel variants (11%) in the genes NEFL, TRPV4, KIF1B, BICD2, and SETX are implicated in the disease but require further evidence of pathogenicity. The remaining 20 variants were confirmed as polymorphisms (not causing the disease) and are detailed here to help interpret sequence variants identified in other family studies. Validation using segregation, normal controls, and bioinformatics tools was valuable as supporting evidence for sequence variants implicated in disease. In addition, we identified one SETX sequence variant (c.7640T>C), previously reported as a putative mutation, which we have confirmed as a nonpathogenic rare polymorphism. This study highlights the advantage of using WES for genetic diagnosis in highly heterogeneous diseases such as IPNs and has been particularly powerful in this cohort where genetic diagnosis could not be achieved due to phenotype and mode of inheritance not being previously obvious. However, first tier testing for common genes in clinically well-defined cases remains important and will account for most positive results. PMID:25802885

  12. Improved inherited peripheral neuropathy genetic diagnosis by whole-exome sequencing.

    PubMed

    Drew, Alexander P; Zhu, Danqing; Kidambi, Aditi; Ly, Carolyn; Tey, Shelisa; Brewer, Megan H; Ahmad-Annuar, Azlina; Nicholson, Garth A; Kennerson, Marina L

    2015-03-01

    Inherited peripheral neuropathies (IPNs) are a group of related diseases primarily affecting the peripheral motor and sensory neurons. They include the hereditary sensory neuropathies (HSN), hereditary motor neuropathies (HMN), and Charcot-Marie-Tooth disease (CMT). Using whole-exome sequencing (WES) to achieve a genetic diagnosis is particularly suited to IPNs, where over 80 genes are involved with weak genotype-phenotype correlations beyond the most common genes. We performed WES for 110 index patients with IPN where the genetic cause was undetermined after previous screening for mutations in common genes selected by phenotype and mode of inheritance. We identified 41 missense sequence variants in the known IPN genes in our cohort of 110 index patients. Nine variants (8%), identified in the genes MFN2, GJB1, BSCL2, and SETX, are previously reported mutations and considered to be pathogenic in these families. Twelve novel variants (11%) in the genes NEFL, TRPV4, KIF1B, BICD2, and SETX are implicated in the disease but require further evidence of pathogenicity. The remaining 20 variants were confirmed as polymorphisms (not causing the disease) and are detailed here to help interpret sequence variants identified in other family studies. Validation using segregation, normal controls, and bioinformatics tools was valuable as supporting evidence for sequence variants implicated in disease. In addition, we identified one SETX sequence variant (c.7640T>C), previously reported as a putative mutation, which we have confirmed as a nonpathogenic rare polymorphism. This study highlights the advantage of using WES for genetic diagnosis in highly heterogeneous diseases such as IPNs and has been particularly powerful in this cohort where genetic diagnosis could not be achieved due to phenotype and mode of inheritance not being previously obvious. However, first tier testing for common genes in clinically well-defined cases remains important and will account for most positive results. PMID:25802885

  13. An intelligent system for lung cancer diagnosis using a new genetic algorithm based feature selection method.

    PubMed

    Lu, Chunhong; Zhu, Zhaomin; Gu, Xiaofeng

    2014-09-01

    In this paper, we develop a novel feature selection algorithm based on the genetic algorithm (GA) using a specifically devised trace-based separability criterion. According to the scores of class separability and variable separability, this criterion measures the significance of feature subset, independent of any specific classification. In addition, a mutual information matrix between variables is used as features for classification, and no prior knowledge about the cardinality of feature subset is required. Experiments are performed by using a standard lung cancer dataset. The obtained solutions are verified with three different classifiers, including the support vector machine (SVM), the back-propagation neural network (BPNN), and the K-nearest neighbor (KNN), and compared with those obtained by the whole feature set, the F-score and the correlation-based feature selection methods. The comparison results show that the proposed intelligent system has a good diagnosis performance and can be used as a promising tool for lung cancer diagnosis. PMID:24994515

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

    E-print Network

    Ephzibah, E P

    2011-01-01

    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.

  15. Selection at 6-PGD locus in laboratory populations of Bactrocera oleae.

    PubMed

    Cosmidis, Nikos; Goulielmos, George; Eliopoulos, Elias; Loukas, Michael

    2008-10-01

    We have previously shown that laboratory populations of the olive fruitfly Bactrocera oleae come to equilibrium with allele frequencies at the 6-phosphogluconate dehydrogenase (6-PGD) locus markedly different from those of wild populations. In this study, we present new evidence from perturbation experiments in support of the notion that the locus is under selective pressure under laboratory conditions. Eleven populations were started with frequencies at the 6-PGD locus different from the laboratory equilibrium. Over 12 generations, the populations showed a return to the previous equilibrium, indicating a direct and powerful selection pressure on the naturally occurring allozymes of this locus. That is, a marked increase of the F allele followed by a compensatory decrease of allele I. Populations were set up to minimize the effects of associative overdominance, and we discuss the possible influence of this factor. Nucleotide sequence for the 6-PGD F and I alleles revealed two missense mutations at positions 501 and 730 leading to different amino acids among the two alleles. PMID:19061528

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

    E-print Network

    Page Jr., C. David

    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

  17. Drug Induced Liver Injury: Review with a Focus on Genetic Factors, Tissue Diagnosis, and Treatment Options

    PubMed Central

    Khoury, Tawfik; Rmeileh, Ayman Abu; Yosha, Liron; Benson, Ariel A.; Daher, Saleh; Mizrahi, Meir

    2015-01-01

    Drug-induced liver injury (DILI) is a rare but potentially life threatening adverse drug reaction. DILI may mimic any morphologic characteristic of acute or chronic liver disease, and the histopathologic features of DILI may be indistinguishable from those of other causes of liver injury, such as acute viral hepatitis. In this review article, we provide an update on causative agents, clinical features, pathogenesis, diagnosis modalities, and outcomes of DILI. In addition, we review results of recently reported genetic studies and updates on pharmacological and invasive treatments. PMID:26356634

  18. Harlequin Ichthyosis: Prenatal Diagnosis of a Rare Yet Severe Genetic Dermatosis

    PubMed Central

    David, Liji Sarah; Beck, Manisha Madhai; Bindra, Mandeep Singh; Arunachal, Gautham

    2015-01-01

    Harlequin Ichthyosis (HI) is an extremely rare genetic skin disorder. It is the most severe type of ichthyosis. It is characterized by thickened, dry, rough and armor like plates of skin with deep cracks in between. Alternative names for HI include- keratosis diffusafetalis, ichthyosis congenital, icthyosis fetalis, harlequin fetus and icthyosis congenital gravior. It is an autosomal recessive disorder with the majority of affected individuals being homozygous for mutation in the ABCA 12 gene. This condition presents with a wide range of severity and symptoms. Affected neonates usually do not survive beyond first few days of life. We are presenting prenatal diagnosis of a case of this rare condition. PMID:26675324

  19. A panel of lung injury biomarkers enhances the definition of primary graft dysfunction (PGD) after lung transplantation

    PubMed Central

    Shah, Rupal J.; Bellamy, Scarlett L.; Localio, A. Russell; Wickersham, Nancy; Diamond, Joshua M.; Weinacker, Ann; Lama, Vibha N.; Bhorade, Sangeeta; Belperio, John A.; Crespo, Maria; Demissie, E.J.; Kawut, Steven M.; Wille, Keith M.; Lederer, David J.; Lee, James C.; Palmer, Scott M.; Orens, Jonathan; Reynolds, John; Shah, Ashish; Wilkes, David S.; Ware, Lorraine B.; Christie, Jason D.

    2012-01-01

    Background We aimed to identify combinations of biomarkers to enhance the definition of PGD for translational research. Methods Biomarkers reflecting lung epithelial injury (sRAGE and SP-D), coagulation cascade (PAI-1 and Protein C), and cell adhesion (ICAM-1) were measured in the plasma of 315 subjects derived from the LTOG cohort at 6 and 24 hours after transplantation. We assessed biomarker utility in two ways: first, we tested the discrimination of grade 3 PGD within 72 hours; second, we tested the predictive utility of plasma biomarkers for 90-day mortality. Results 86/315 subjects (27%) developed PGD. 23 subjects (8%) died within 90 days of transplantation, of which 16 (70%) had PGD. Biomarkers measured at 24 hours had greater discrimination than at 6 hours. Individually, sRAGE (AUC 0.71) and PAI-1 (AUC 0.73) had the best discrimination of PGD. The combinations of sRAGE with PAI-1 (AUC 0.75), PAI-1 with ICAM-1 (AUC 0.75), and PAI-1 with SP-D (AUC 0.76) had the best discrimination. Combinations of greater than 2 biomarkers did not significantly enhance discrimination of PGD. ICAM-1 with PAI-1 (AUC 0.72) and ICAM-1 with sRAGE (AUC of 0.72) had the best prediction for 90-day mortality. The addition of ICAM-1, PAI-1, or sRAGE to the concurrent clinical PGD grade significantly improved prediction of 90-day mortality (p<0.001 each). Conclusions Measurement of the combination of a marker of impaired fibrinolysis with an epithelial injury or cell adhesion marker had the best discrimination for PGD and prediction for early mortality, and may provide an alternative outcome useful in future research. PMID:22694851

  20. Ten common genetic variants associated with colorectal cancer risk are not associated with survival after diagnosis

    PubMed Central

    Tenesa, Albert; Theodoratou, Evropi; Din, Farhat VN; Farrington, Susan M; Cetnarskyj, Roseanne; Barnetson, Rebecca A; Porteous, Mary E; Campbell, Harry; Dunlop, Malcolm G

    2010-01-01

    Purpose To date, genome-wide association studies have identified ten genetic loci associated with colorectal cancer (CRC) susceptibility. We hypothesised that these loci might also impact on cancer survival. Experimental design To determine whether SNPs tagging these ten loci influenced all-cause and CRC-specific mortality, we prospectively followed survival outcomes for 2838 Scottish patients recruited soon after a diagnosis of colorectal cancer. Survival analysis was conducted using Cox proportional hazard models adjusted for American Joint Committee on Cancer stage, age and sex. Results None of the SNPs were found to be statistically significantly associated with all-cause or CRC-specific mortality. Conclusions We conclude that none of the ten common genetic variants so far shown to be associated with colorectal cancer risk are associated with survival from colorectal cancer. PMID:20628028

  1. Use of genetic algorithms for computer-aided diagnosis of breast cancers from image features

    NASA Astrophysics Data System (ADS)

    Floyd, Carey E., Jr.; Tourassi, Georgia D.; Baker, Jay A.

    1996-04-01

    In this investigation we explore genetic algorithms as a technique to train the weights in a feed forward neural network designed to predict breast cancer based on mammographic findings and patient history. Mammograms were obtained from 206 patients who obtained breast biopsies. Mammographic findings were recorded by radiologists for each patient. In addition, the outcome of the biopsy was recorded. Of the 206 cases, 73 were malignant while 133 were benign at the time of biopsy. A genetic algorithm (GA) was developed to adjust the weights of an artificial neural network (ANN) so that the ANN would output the outcome of the biopsy when the mammographic findings were given as inputs. The GA is a technique for function optimization that reflects biological genetic evolution. The ANN was a fully connected feed- forward network using a sigmoid activation with 11 inputs, one hidden layer with 10 nodes, and one output node (benign/malignant). The GA approach allows much flexibility in selecting the function to be optimized. In this work both mean-squared error (MSE) and receiver operating characteristic (ROC) curve area (Az) were explored as optimization criteria. The system was trained using a bootstrap sampling. Optimizing for the two criteria result in different solutions. The 'best' solution was obtained by minimizing a linear combination of MSE and (1-Az). ROC areas were 0.82 plus or minus 0.07, somewhat less than those obtained using backpropagation for ANN training: 0.90 plus or minus 0.05. This is the first description of a genetic algorithm for breast cancer diagnosis. The novel advantage of this technique is the ability to optimize the system for maximizing ROC area rather than minimizing mean squared error. A new technique for computer-aided diagnosis of breast cancer has been explored. The flexibility of the GA approach allows optimization of cost functions that have relevance to breast cancer prediction.

  2. Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic

    PubMed Central

    Foley, Samantha B.; Rios, Jonathan J.; Mgbemena, Victoria E.; Robinson, Linda S.; Hampel, Heather L.; Toland, Amanda E.; Durham, Leslie; Ross, Theodora S.

    2014-01-01

    Despite the potential of whole-genome sequencing (WGS) to improve patient diagnosis and care, the empirical value of WGS in the cancer genetics clinic is unknown. We performed WGS on members of two cohorts of cancer genetics patients: those with BRCA1/2 mutations (n = 176) and those without (n = 82). Initial analysis of potentially pathogenic variants (PPVs, defined as nonsynonymous variants with allele frequency < 1% in ESP6500) in 163 clinically-relevant genes suggested that WGS will provide useful clinical results. This is despite the fact that a majority of PPVs were novel missense variants likely to be classified as variants of unknown significance (VUS). Furthermore, previously reported pathogenic missense variants did not always associate with their predicted diseases in our patients. This suggests that the clinical use of WGS will require large-scale efforts to consolidate WGS and patient data to improve accuracy of interpretation of rare variants. While loss-of-function (LoF) variants represented only a small fraction of PPVs, WGS identified additional cancer risk LoF PPVs in patients with known BRCA1/2 mutations and led to cancer risk diagnoses in 21% of non-BRCA cancer genetics patients after expanding our analysis to 3209 ClinVar genes. These data illustrate how WGS can be used to improve our ability to discover patients' cancer genetic risks. PMID:26023681

  3. Prenatal diagnosis and genetic analysis of double trisomy 48,XXX,+18.

    PubMed

    Chen, C P; Chern, S R; Yeh, L F; Chen, W L; Chen, L F; Wang, W

    2000-09-01

    Prenatal diagnosis of simultaneous occurrence of double trisomy involving chromosomes 18 and X is extremely rare. We report on the prenatal diagnosis, genetic analysis and clinical manifestations of a fetus with both trisomy 18 and trisomy X. A 26-year-old, para 1 woman was referred for genetic counselling at 36 weeks' gestation with the sonographic findings of intrauterine growth retardation (IUGR), polyhydramnios, ventricular septal defect, and an enlarged cisterna magna. Both cordocentesis and amniocentesis revealed a consistent karyotype of 48,XXX,+18. Quantitative fluorescent polymerase chain reaction using polymorphic small tandem repeat markers specific for chromosomes 18 and X rapidly determined that both aneuploidies arose as a result of non-disjunction in maternal meiosis II. Our case shows that two non-disjunction events can occur not only in the same parent, but also in the same cell division. Our case also shows that double trisomy, 48,XXX,+18, can demonstrate an enlarged cisterna magna, IUGR and polyhydramnios in prenatal ultrasound. PMID:11015706

  4. A 26-Year Experience in Chorionic Villus Sampling Prenatal Genetic Diagnosis

    PubMed Central

    Jorge, Paula; Mota-Freitas, Maria Manuela; Santos, Rosário; Silva, Maria Luz; Soares, Gabriela; Fortuna, Ana Maria

    2014-01-01

    This report describes the trends of chorionic villus sampling (CVS) referred for prenatal genetic diagnosis in the past two and a half decades in a Portuguese Center. Our cohort of 491 CVS was mostly performed by the transcervical method at the 12th gestational week. Data collected within the framework of this study relate to the following: sampling method, referral reason versus abnormality and incidence of procedure-related pregnancy loss, that declined to about 0.5% over the last 15 years. The year 2000 represented a change in referral reasons for chorionic tissue collection, shifting from almost exclusively for cytogenetic testing to an increasing number of molecular tests for monogenic disorders. Herein, success rates as well as cytogenetic and/or molecular DNA results are presented. These latter include not only tests for several monogenic disorders, but also aneuploidy and maternal cell contamination screening. This retrospective analysis reiterates that CVS is a safe and reliable first trimester technique for prenatal diagnosis in high genetic risk pregnancies. PMID:26237480

  5. Immunohistochemical Markers of Soft Tissue Tumors: Pathologic Diagnosis, Genetic Contributions, and Therapeutic Options

    PubMed Central

    Parham, David M

    2015-01-01

    After ~30 years of widespread usage, immunohistochemistry (IHC) has become a standard method of diagnosis for surgical pathology. Because of the plethora of diagnoses and often subtle nature of diagnostic criteria, IHC finds particular utility in soft tissue tumors. The use of progressively small amounts of tissue for diagnosis highlights the importance of this method. The sensitivity and crispness of IHC stains have progressively improved with the advent of new techniques. Traditionally, IHC detects cell-typic markers that characterize cell phenotypes, such as chromogranin for neuroectodermal tissue, myogenin for skeletal muscle, and cytokeratin for epithelium. However, the advent of genetic discoveries have led to IHC testing for detection of fusion gene products or overexpressed oncogenes associated with deletions and mutations. Proliferation-based markers such as Ki-67 can also be used for prognosis and grading, but more standardization is needed. Development of monoclonal antibody-based pharmaceuticals, such as imatinib or crizotinib, holds the promise of tailored anticancer therapy. IHC thus has assumed importance not only for diagnosis but also for guidance of personalized medicine. PMID:26549970

  6. Molecular genetic study of novel biomarkers for early diagnosis of oral squamous cell carcinoma

    PubMed Central

    Yong-Deok, Kim; Eun-Hyoung, Jeon; Yeon-Sun, Kim; Kang-Mi, Pang; Jin-Yong, Lee; Sung-Hwan, Cho; Tae-Yun, Kim; Tae-Sung, Park; Soung-Min, Kim; Myung-Jin, Kim

    2015-01-01

    Objectives: Early detection and treatment of an oral squamous cell carcinoma (OSCC) is critical because of its rapid growth, frequent lymph-node metastasis, and poor prognosis. However, no clinically-valuable methods of early diagnosis exist, and genetic analysis of OSCCs has yielded no biomarkers. Study Design: We investigated the expression of genes associated with inflammation in OSCCs via a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis of microarray data. Tumor and normal tissues from five patients with an OSCC were used for microarray analysis. Differentially-expressed genes, identified using permutation, local pooled error (LPE), t-tests, and significance analysis of microarrays (SAM), were selected as candidate genetic markers. Results: Two groups corresponding to tissue identity were evident, implying that their differentially-expressed genes represented biological differences between tissues. Fifteen genes were identified using the Student’s paired t-test (p<0.05) and the SAM, with a false discovery rate of less than 0.02. Based on gene expression, these 15 genes can be used to classify an OSCC. A genetic analysis of functional networks and ontologies, validated by using a qRT-PCR analysis of the tissue samples, identified four genes, ADAM15, CDC7, IL12RB2 and TNFRSF8, that demonstrated excellent concordance with the microarray data. Conclusions: Our study demonstrated that four genes (ADAM15, CDC7, IL12RB2 and TNFRSF8) had potential as novel biomarkers for the diagnosis and the treatment of an OSCC. Key words:Biomarker, microarray, quantitative reverse transcription polymerase chain reaction, oral squamous cell carcinoma, gene expression profiling. PMID:25475780

  7. Genetics of primary bilateral macronodular adrenal hyperplasia: a model for early diagnosis of Cushing's syndrome?

    PubMed

    Drougat, Ludivine; Espiard, Stéphanie; Bertherat, Jerôme

    2015-10-01

    Long-term consequences of cortisol excess are frequent despite appropriate treatment after cure of Cushing's syndrome. This might be due to diagnostic delay, often difficult to reduce in rare diseases. The identification of a genetic predisposing factor might help to improve early diagnosis by familial screening. Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing's syndrome. Hypercortisolism in PBMAH is most often diagnosed between the fifth and sixth decades of life. The bilateral nature of the adrenocortical tumors and the occurrence of rare clear familial forms suggest a genetic origin. Indeed, a limited subset of PBMAH can be observed as part of multiple tumors syndromes due to alterations of the APC, Menin or Fumarate Hydratase genes. Rare variants of the phosphodiesterases PDE11A have been associated with PBMAH. The recent identification of ARMC5 germline alterations in 25-50% of PBMAH patients without obvious familial history or associated tumors opens new perspectives. ARMC5 alterations follow the model of a tumor suppressor gene: a first germline inactivating mutation of this 16p located gene is followed by a somatic secondary hit on the other allele (inactivating mutation or allelic loss). Functional studies demonstrate that ARMC5 controls apoptosis and steroid synthesis. The phenotype of index cases patients with the mutation seems more severe than the one of WT index cases. However, phenotype variability within a family is often observed. This review summarizes the genetics of PBMAH, focusing on ARMC5, which offer new perspectives for early diagnosis of Cushing's syndrome. PMID:26264719

  8. Genetic diagnosis of familial hypercholesterolaemia by targeted next-generation sequencing

    PubMed Central

    Maglio, C; Mancina, R M; Motta, B M; Stef, M; Pirazzi, C; Palacios, L; Askaryar, N; Borén, J; Wiklund, O; Romeo, S

    2014-01-01

    Maglio C., Mancina R. M., Motta B. M., Stef M., Pirazzi C., Palacios L., Askaryar N., Borén J., Wiklund O., Romeo S. (University of Gothenburg, Gothenburg, Sweden; University Magna Graecia of Catanzaro, Italy; University of Milan, Italy; Progenika Biopharma SA, Derio, Spain). Genetic diagnosis of familial hypercholesterolaemia by targeted next-generation sequencing. Objectives The aim of this study was to combine clinical criteria and next-generation sequencing (pyrosequencing) to establish a diagnosis of familial hypercholesterolaemia (FH). Design, setting and subjects A total of 77 subjects with a Dutch Lipid Clinic Network score of ?3 (possible, probable or definite FH clinical diagnosis) were recruited from the Lipid Clinic at Sahlgrenska Hospital, Gothenburg, Sweden. Next-generation sequencing was performed in all subjects using SEQPRO LIPO RS, a kit that detects mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9) and LDLR adapter protein 1 (LDLRAP1) genes; copy-number variations in the LDLR gene were also examined. Results A total of 26 mutations were detected in 50 subjects (65% success rate). Amongst these, 23 mutations were in the LDLR gene, two in the APOB gene and one in the PCSK9 gene. Four mutations with unknown pathogenicity were detected in LDLR. Of these, three mutations (Gly505Asp, Ile585Thr and Gln660Arg) have been previously reported in subjects with FH, but their pathogenicity has not been proved. The fourth, a mutation in LDLR affecting a splicing site (exon 6–intron 6) has not previously been reported; it was found to segregate with high cholesterol levels in the family of the proband. Conclusions Using a combination of clinical criteria and targeted next-generation sequencing, we have achieved FH diagnosis with a high success rate. Furthermore, we identified a new splicing-site mutation in the LDLR gene. PMID:24785115

  9. Genetic diagnosis and prognosis of Alzheimer’s disease: challenges and opportunities

    PubMed Central

    Reitz, Christiane

    2015-01-01

    Alzheimer’s disease (AD), the most common form of dementia in western societies, is a pathologically and clinically heterogeneous disease with a strong genetic component. The recent advances in high-throughput genome technologies allowing for the rapid analysis of millions of polymorphisms in thousands of subjects has significantly advanced our understanding of the genomic underpinnings of AD susceptibility. During the last 5 years, genome-wide association and whole-exome- and whole-genome sequencing studies have mapped more than 20 disease-associated loci, providing insights into the molecular pathways involved in AD pathogenesis and hinting at potential novel therapeutic targets. This review article summarizes the challenges and opportunities of when using genomic information for diagnosis and prognosis of Alzheimer’s disease. PMID:25634383

  10. Arrhythmogenic right ventricular cardiomyopathy: an update on pathophysiology, genetics, diagnosis, and risk stratification.

    PubMed

    Paul, M; Wichter, T; Fabritz, L; Waltenberger, J; Schulze-Bahr, E; Kirchhof, P

    2012-09-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy accounting for life-threatening ventricular tachyarrhythmias and sudden death in young individuals and athletes. Over the past years, mutations in desmosomal genes have been identified as disease-causative. However, genetic heterogeneity and variable phenotypic expression alongside with diverse disease progression still render the evaluation of its prognostic implication difficult. ARVC was initially entered into the canon of cardiomyopathies of the World Health Organization in 1995, and international efforts have resulted in the 2010 modified diagnostic criteria for ARVC. Despite all additional insights into pathophysiology, clinical management, and modern risk stratification, under-/misdiagnosing of ARVC remains a problem and hampers reliable statements on the incidence, prevalence, and natural course of the disease.This review provides a comprehensive overview of the current literature on the pathogenesis, diagnosis, treatment, and prognosis of ARVC and sheds some light on potential new developments in these areas. PMID:23011601

  11. Feature selection from nocturnal oximetry using genetic algorithms to assist in obstructive sleep apnoea diagnosis.

    PubMed

    Álvarez, Daniel; Hornero, Roberto; Marcos, J Víctor; Del Campo, Félix

    2012-10-01

    Nocturnal pulse oximetry (NPO) has demonstrated to be a powerful tool to help in obstructive sleep apnoea (OSA) detection. However, additional analysis is needed to use NPO alone as an alternative to nocturnal polysomnography (NPSG), which is the gold standard for a definitive diagnosis. In the present study, we exhaustively analysed a database of blood oxygen saturation (SpO(2)) recordings (80 OSA-negative and 160 OSA-positive) to obtain further knowledge on the usefulness of NPO. Population set was randomly divided into training and test sets. A feature extraction stage was carried out: 16 features (time and frequency statistics and spectral and nonlinear features) were computed. A genetic algorithm (GA) approach was applied in the feature selection stage. Our methodology achieved 87.5% accuracy (90.6% sensitivity and 81.3% specificity) in the test set using a logistic regression (LR) classifier with a reduced number of complementary features (3 time domain statistics, 1 frequency domain statistic, 1 conventional spectral feature and 1 nonlinear feature) automatically selected by means of GAs. Our results improved diagnostic performance achieved with conventional oximetric indexes commonly used by physicians. We concluded that GAs could be an effective and robust tool to search for essential oximetric features that could enhance NPO in the context of OSA diagnosis. PMID:22154238

  12. Angelman syndrome in Denmark. birth incidence, genetic findings, and age at diagnosis.

    PubMed

    Mertz, Line Granild Bie; Christensen, Rikke; Vogel, Ida; Hertz, Jens Michael; Nielsen, Karen Brøndum; Grønskov, Karen; Østergaard, John R

    2013-09-01

    Angelman syndrome (AS) is a neurogenetic disorder caused by loss of expression of the maternal imprinted gene UBE3A on chromosome 15q11.2-q13. Clinical features of AS include severe intellectual disability, a happy disposition, ataxia, mandibular prognatism, and epilepsy. Our objectives were to examine the birth incidence of AS in Denmark and to characterize the size of the 15q11.2-q13 deletions with 1,000K array CGH. In addition, we analyzed genotype differences in regard to age at diagnosis and investigated the occurrence of deletions/duplications outside the 15q11.2-q13 regions. We identified 51 patients with genetically verified AS, which corresponded to a birth incidence of 1:24,580 (95%CI: 1:23,727-1:25,433). Thirty-six patients showed a deletion; 13 had a Class I deletion and 20 had a Class II deletion. There was bimodal distribution of the BP3 breakpoint. Three patients had larger and atypical deletions, with distal breakpoints telomeric to BP3. Five patients had paternal uniparental disomy (pUPD) of chromosome 15, and four had a verified UBE3A mutation. Additional deletions/duplications outside the 15q11.2-q13 areas were demonstrated in half the participants. Six harbored more than one CNV. Mean age at diagnosis was 21 months (95%CI: 17-23 months) for children with a deletion and 46 months (95%CI: 36-55 months) for children with pUPD or a UBE3A mutation (P < 0.01). The presence of a CNV outside 15q11.2-q13 did not have an impact on age at diagnosis. PMID:23913711

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

    PubMed Central

    Roma-Rodrigues, Catarina; Fernandes, Alexandra R

    2014-01-01

    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

  14. Preimplantation genetic diagnosis in Welsh pony embryos after biopsy and cryopreservation.

    PubMed

    Guignot, F; Reigner, F; Perreau, C; Tartarin, P; Babilliot, J M; Bed'hom, B; Vidament, M; Mermillod, P; Duchamp, G

    2015-11-01

    Preimplantation genetic diagnosis and embryo cryopreservation are important tools to improve genetic management in equine species with marked consequences on the economic value, health, biodiversity, and preservation of the animals. This study aimed to develop a biopsy method at the blastocyst stage that provides viable genotyped cryopreserved Welsh pony embryos. Embryos were collected at d 6.75 to 7 after ovulation. Biopsies were performed with either a microblade or a micropipette. After biopsy, embryos were cryopreserved. The survival rate of biopsied embryos was evaluated on fresh and cryopreserved embryos either 24 h after in vitro culture or after transfer to recipients. Fresh and nonbiopsied embryos were used as controls. Sex, coat color genes, myotony (neuromuscular disorder) diagnosis, and markers of parentage were investigated using PCR on biopsied cells after whole-genome amplification and on remaining embryos. The embryo survival rate after transfer was not affected by the micropipette biopsy (50%, = 8; 43%, = 7; and 50%, = 12, at d 30 for fresh biopsied embryos, vitrified biopsied embryos, and control embryos, respectively) but was significantly reduced by the use of microblade biopsy: 9 ( = 11) vs. 67% ( = 12) for control embryos. Successful sex determination was achieved for 82% ( = 28) of the micropipette biopsies and 100% ( = 50) of the microblade biopsies. Sex determined on biopsied cells was found to correspond completely (100%) with that determined on the remaining embryo ( = 37). More than 90% of the parentage checking markers, coat color, and myotony diagnosis were successfully determined on biopsies obtained with either a micropipette or a microblade. Mendelian incompatibility (7.5 and 5.5%) and embryo genotyping errors (6.6 and 8.6%) were low and not significantly different between the 2 methods. In conclusion, for the first time, pregnancy at Day 30 was obtained after transfer of Welsh pony biopsied and vitrified embryos >300 ?m in diameter to recipient pony mares. The biopsied cells collected enabled multigenetic embryo diagnoses to be performed to a high degree of accuracy. The micropipette biopsy is the better method to apply on Welsh pony embryos. PMID:26641042

  15. Fine needle biopsy and genetics, two allied weapons in the diagnosis, prognosis, and target therapeutics of solid pediatric tumors.

    PubMed

    Barroca, Helena

    2008-09-01

    The recognition that genetic defects identify some pediatric solid tumors and may represent prognostic markers has provided cytologists with an extra tool for dealing with such tumors. Using some entities as archetypes, we discuss the importance of the association of fine needle biopsy and genetics, in the diagnosis, prognosis, and therapy selection of solid pediatric tumors. Immunocytochemistry is important to differentiate neuroblastoma, PNET/Ewing sarcoma, alveolar rhabdomyosarcoma, lymphoma, and desmoplastic small round cell tumor. Despite its usefulness in many cases, it is not conclusive and some of the aforementioned tumors even share the expression of some antibodies. The detection of specific diagnostic translocations will thus provide additional information and allows a precise cytologic diagnosis. Kidney tumors are also frequent in children. Although no genetic abnormalities have been identified so far in nephroblastoma, other kidney tumors, such as mesoblastic nephroma, whose cytology pattern can masquerade nephroblastoma, are also characterized by specific translocations. Kidney tumors in children have also been associated recently with typical genetic alterations such as Xp11.2RCC. Concerning prognosis and therapy selection, neuroblastoma is a sort of paradigm. The identification of MYCN oncogene status as an independent prognostic factor is determinant, not only in the assessment of clinical evolution, but also in the identification of risk groups, and consequently in the appropriate therapy selection. Cytopathologists should be aware of the genetic alterations characterizing pediatric tumors in order to collect extra material to perform cytogenetics, FISH, PCR, and Southern blotting, to achieve the correct identification of such genetic changes. PMID:18677757

  16. Familial haemophagocytic lymphohistiocytosis: advances in the genetic basis, diagnosis and management

    PubMed Central

    Gholam, C; Grigoriadou, S; Gilmour, K C; Gaspar, H B

    2011-01-01

    Familial haemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive disorder of immune dysregulation associated with uncontrolled T cell and macrophage activation and hypercytokinaemia. The incidence of FHL is 0·12/100·000 children born per year, with a male to female ratio of 1:1. The disease is classified into six different types based on genetic linkage analysis and chromosomal localization; five specific genetic defects have been identified, which account for approximately 90% of all patients. Type 1 is due to an as yet unidentified gene defect located on chromosome nine. Type 2 is caused by mutations in the perforin (PRF1) gene, type 3 by mutations in the Munc-13–4 (UNC13D) gene, type 4 by mutations in the syntaxin 11 (STX11) gene and the recently described type 5 due to mutations in the gene encoding syntaxin binding protein 2 (STXBP-2). The incidence of the five types varies in different ethnic groups. The most common presenting features are pyrexia of unknown origin, pronounced hepatosplenomegaly and cytopenias. Neurological features tend to present later and are associated with poor prognosis. Absent or decreased lymphocyte cytotoxicity is the cellular hallmark of FHL. Biochemical features such as hyperferritinaemia, hypertriglyceridaemia and hypofibrinogenaemia are usually present, along with high levels of soluble interleukin 2 receptor in the blood and cerebrospinal fluid. Bone marrow aspirate may demonstrate the characteristic haemophagocytes, but initially is non-diagnostic in two-thirds of patients. Established international clinical, haematological and biochemical criteria now facilitate accurate clinical diagnosis. The disease is fatal unless a haematopoietic stem cell transplant (HSCT) is performed. The introduction of HSCT has dramatically improved the prognosis of the disease. However, the mortality of the disease is still significantly high and a number of challenges remain to be addressed. Active disease at the time of the transplant is the major significant poor prognostic factor. Delayed diagnosis, after irreversible organ damage has occurred, especially neurological damage, disease reoccurrence and pre-transplant mortality, remain a concern. PMID:21303357

  17. Multi-Stage Feature Selection by Using Genetic Algorithms for Fault Diagnosis in Gearboxes Based on Vibration Signal

    PubMed Central

    Cerrada, Mariela; Sánchez, René Vinicio; Cabrera, Diego; Zurita, Grover; Li, Chuan

    2015-01-01

    There are growing demands for condition-based monitoring of gearboxes, and techniques to improve the reliability, effectiveness and accuracy for fault diagnosis are considered valuable contributions. Feature selection is still an important aspect in machine learning-based diagnosis in order to reach good performance in the diagnosis system. The main aim of this research is to propose a multi-stage feature selection mechanism for selecting the best set of condition parameters on the time, frequency and time-frequency domains, which are extracted from vibration signals for fault diagnosis purposes in gearboxes. The selection is based on genetic algorithms, proposing in each stage a new subset of the best features regarding the classifier performance in a supervised environment. The selected features are augmented at each stage and used as input for a neural network classifier in the next step, while a new subset of feature candidates is treated by the selection process. As a result, the inherent exploration and exploitation of the genetic algorithms for finding the best solutions of the selection problem are locally focused. The approach is tested on a dataset from a real test bed with several fault classes under different running conditions of load and velocity. The model performance for diagnosis is over 98%. PMID:26393603

  18. Multi-Stage Feature Selection by Using Genetic Algorithms for Fault Diagnosis in Gearboxes Based on Vibration Signal.

    PubMed

    Cerrada, Mariela; Vinicio Sánchez, René; Cabrera, Diego; Zurita, Grover; Li, Chuan

    2015-01-01

    There are growing demands for condition-based monitoring of gearboxes, and techniques to improve the reliability, effectiveness and accuracy for fault diagnosis are considered valuable contributions. Feature selection is still an important aspect in machine learning-based diagnosis in order to reach good performance in the diagnosis system. The main aim of this research is to propose a multi-stage feature selection mechanism for selecting the best set of condition parameters on the time, frequency and time-frequency domains, which are extracted from vibration signals for fault diagnosis purposes in gearboxes. The selection is based on genetic algorithms, proposing in each stage a new subset of the best features regarding the classifier performance in a supervised environment. The selected features are augmented at each stage and used as input for a neural network classifier in the next step, while a new subset of feature candidates is treated by the selection process. As a result, the inherent exploration and exploitation of the genetic algorithms for finding the best solutions of the selection problem are locally focused. The Sensors 2015, 15 23904 approach is tested on a dataset from a real test bed with several fault classes under different running conditions of load and velocity. The model performance for diagnosis is over 98%. PMID:26393603

  19. Genetic Diagnosis of Charcot-Marie-Tooth Disease in a Population by Next-Generation Sequencing

    PubMed Central

    Høyer, Helle; Braathen, Geir J.; Busk, Øyvind L.; Holla, Øystein L.; Svendsen, Marit; Hilmarsen, Hilde T.; Strand, Linda; Skjelbred, Camilla F.; Russell, Michael B.

    2014-01-01

    Charcot-Marie-Tooth (CMT) disease is the most prevalent inherited neuropathy. Today more than 40 CMT genes have been identified. Diagnosing heterogeneous diseases by conventional Sanger sequencing is time consuming and expensive. Thus, more efficient and less costly methods are needed in clinical diagnostics. We included a population based sample of 81?CMT families. Gene mutations had previously been identified in 22 families; the remaining 59 families were analysed by next-generation sequencing. Thirty-two CMT genes and 19 genes causing other inherited neuropathies were included in a custom panel. Variants were classified into five pathogenicity classes by genotype-phenotype correlations and bioinformatics tools. Gene mutations, classified certainly or likely pathogenic, were identified in 37 (46%) of the 81 families. Point mutations in known CMT genes were identified in 21 families (26%), whereas four families (5%) had point mutations in other neuropathy genes, ARHGEF10, POLG, SETX, and SOD1. Eleven families (14%) carried the PMP22 duplication and one family carried a MPZ duplication (1%). Most mutations were identified not only in known CMT genes but also in other neuropathy genes, emphasising that genetic analysis should not be restricted to CMT genes only. Next-generation sequencing is a cost-effective tool in diagnosis of CMT improving diagnostic precision and time efficiency. PMID:25025039

  20. The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis.

    PubMed

    Wiesinger, Christoph; Eichler, Florian S; Berger, Johannes

    2015-01-01

    X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene encoding a peroxisomal ABC transporter. In this review, we compare estimates of incidence derived from different populations in order to provide an overview of the worldwide incidence of X-ALD. X-ALD presents with heterogeneous phenotypes ranging from adrenomyeloneuropathy (AMN) to inflammatory demyelinating cerebral ALD (CALD). A large number of different mutations has been described, providing a unique opportunity for analysis of functional domains within ABC transporters. Yet the molecular basis for the heterogeneity of clinical symptoms is still largely unresolved, as no correlation between genotype and phenotype exists in X-ALD. Beyond ABCD1, environmental triggers and other genetic factors have been suggested as modifiers of the disease course. Here, we summarize the findings of numerous reports that aimed at identifying modifier genes in X-ALD and discuss potential problems and future approaches to address this issue. Different options for prenatal diagnosis are summarized, and potential pitfalls when applying next-generation sequencing approaches are discussed. Recently, the measurement of very long-chain fatty acids in lysophosphatidylcholine for the identification of peroxisomal disorders was included in newborn screening programs. PMID:25999754

  1. The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis

    PubMed Central

    Wiesinger, Christoph; Eichler, Florian S; Berger, Johannes

    2015-01-01

    X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene encoding a peroxisomal ABC transporter. In this review, we compare estimates of incidence derived from different populations in order to provide an overview of the worldwide incidence of X-ALD. X-ALD presents with heterogeneous phenotypes ranging from adrenomyeloneuropathy (AMN) to inflammatory demyelinating cerebral ALD (CALD). A large number of different mutations has been described, providing a unique opportunity for analysis of functional domains within ABC transporters. Yet the molecular basis for the heterogeneity of clinical symptoms is still largely unresolved, as no correlation between genotype and phenotype exists in X-ALD. Beyond ABCD1, environmental triggers and other genetic factors have been suggested as modifiers of the disease course. Here, we summarize the findings of numerous reports that aimed at identifying modifier genes in X-ALD and discuss potential problems and future approaches to address this issue. Different options for prenatal diagnosis are summarized, and potential pitfalls when applying next-generation sequencing approaches are discussed. Recently, the measurement of very long-chain fatty acids in lysophosphatidylcholine for the identification of peroxisomal disorders was included in newborn screening programs. PMID:25999754

  2. Protein and genetic diagnosis of limb girdle muscular dystrophy type 2A: The yield and the pitfalls.

    PubMed

    Fanin, Marina; Angelini, Corrado

    2015-08-01

    Limb girdle muscular dystrophy type 2A (LGMD2A) is the most frequent form of LGMD worldwide. Comprehensive clinical assessment and laboratory testing is essential for diagnosis of LGMD2A. Muscle immunoblot analysis of calpain-3 is the most useful tool to direct genetic testing, as detection of calpain-3 deficiency has high diagnostic value. However, calpain-3 immunoblot testing lacks sensitivity in about 30% of cases due to gene mutations that inactivate the enzyme. The best diagnostic strategy should be determined on a case-by-case basis, depending on which tissues are available, and which molecular and/or genetic methods are adopted. In this work we survey the current knowledge, advantages, limitations, and pitfalls of protein testing and mutation detection in LGMD2A and provide an update of genetic epidemiology. PMID:25900067

  3. Identification of defensin-encoding genes of Picea glauca: characterization of PgD5, a conserved spruce defensin with strong antifungal activity

    PubMed Central

    2012-01-01

    Background Plant defensins represent a major innate immune protein superfamily that displays strong inhibitory effects on filamentous fungi. The total number of plant defensins in a conifer species is unknown since there are no sequenced conifer genomes published, however the genomes of several angiosperm species provide an insight on the diversity of plant defensins. Here we report the identification of five new defensin-encoding genes from the Picea glauca genome and the characterization of two of their gene products, named PgD5 and endopiceasin. Results Screening of a P. glauca EST database with sequences of known plant defensins identified four genes with homology to the known P. glauca defensin PgD1, which were designated PgD2-5. Whereas in the mature PgD2-4 only 7–9 amino acids differed from PgD1, PgD5 had only 64% sequence identity. PgD5 was amplified from P. glauca genomic DNA by PCR. It codes for a precursor of 77-amino acid that is fully conserved within the Picea genus and has similarity to plant defensins. Recombinant PgD5, produced in Escherichia coli, had a molecular mass of 5.721 kDa, as determined by mass spectrometry. The PgD5 peptide exhibited strong antifungal activity against several phytopathogens without any effect on the morphology of the treated fungal hyphae, but strongly inhibited hyphal elongation. A SYTOX uptake assay suggested that the inhibitory activity of PgD5 could be associated with altering the permeability of the fungal membranes. Another completely unrelated defensin gene was identified in the EST library and named endopiceasin. Its gene codes for a 6-cysteine peptide that shares high similarity with the fungal defensin plectasin. Conclusions Screening of a P. glauca EST database resulted in the identification of five new defensin-encoding genes. PgD5 codes for a plant defensin that displays non-morphogenic antifungal activity against the phytopathogens tested, probably by altering membrane permeability. PgD5 has potential for application in the plant biotechnology sector. Endopiceasin appears to derive from an endo- or epiphytic fungal strain rather than from the plant itself. PMID:23035776

  4. X-linked glucose-6-phosphate dehydrogenase (G6PD) and autosomal 6-phosphogluconate dehydrogenase (6PGD) polymorphisms in baboons

    SciTech Connect

    VandeBerg, J.L.; Aivaliotis, M.J.; Samollow, P.B. )

    1992-12-01

    Electrophoretic polymorphisms of glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) were examined in captive colonies of five subspecies of baboons (Papio hamadryas). Phenotype frequencies and family data verified the X-linked inheritance of the G6PD polymorphism. Insufficient family data were available to confirm autosomal inheritance of the 6PGD polymorphism, but the electrophoretic patterns of variant types (putative heterozygotes) suggested the codominant expression of alleles at an autosomal locus. Implications of the G6PD polymorphism are discussed with regard to its utility as a marker system for research on X-chromosome inactivation during baboon development and for studies of clonal cell proliferation and/or cell selection during the development of atherosclerotic lesions in the baboon model. 61 refs., 1 fig., 4 tabs.

  5. Dominant feature selection for the fault diagnosis of rotary machines using modified genetic algorithm and empirical mode decomposition

    NASA Astrophysics Data System (ADS)

    Lu, Lei; Yan, Jihong; de Silva, Clarence W.

    2015-05-01

    This paper develops a novel dominant feature selection method using a genetic algorithm with a dynamic searching strategy. It is applied in the search for the most representative features in rotary mechanical fault diagnosis, and is shown to improve the classification performance with fewer features. First, empirical mode decomposition (EMD) is employed to decompose a vibration signal into intrinsic mode functions (IMFs) which represent the signal characteristic with sample oscillatory modes. Then, a modified genetic algorithm with variable-range encoding and dynamic searching strategy is used to establish relationships between optimized feature subsets and the classification performance. Next, a statistical model that uses receiver operating characteristic (ROC) is developed to select dominant features. Finally, support vector machine (SVM) is used to classify different fault patterns. Two real-world problems, rotor-unbalance vibration and bearing corrosion, are employed to evaluate the proposed feature selection scheme and fault diagnosis system. Statistical results obtained by analyzing the two problems, and comparative studies with five well-known feature selection techniques, demonstrate that the method developed in this paper can achieve improvements in identification accuracy with lower feature dimensionality. In addition, the results indicate that the proposed method is a promising tool to select dominant features in rotary machinery fault diagnosis.

  6. Are There Cultural Differences in Parental Interest in Early Diagnosis and Genetic Risk Assessment for Autism Spectrum Disorder?

    PubMed Central

    Amiet, Claire; Couchon, Elizabeth; Carr, Kelly; Carayol, Jerôme; Cohen, David

    2014-01-01

    Background: There are many societal and cultural differences between healthcare systems and the use of genetic testing in the US and France. These differences may affect the diagnostic process for autism spectrum disorder (ASD) in each country and influence parental opinions regarding the use of genetic screening tools for ASD. Methods: Using an internet-based tool, a survey of parents with at least one child with ASD was conducted. A total of 162 participants from the US completed an English version of the survey and 469 participants from France completed a French version of the survey. Respondents were mainly females (90%) and biological parents (94.3% in the US and 97.2% in France). Results: The mean age of ASD diagnosis reported was not significantly different between France (57.5?±?38.4?months) and the US (56.5?±?52.7?months) (p?=?0.82) despite significant difference in the average age at which a difference in development was first suspected [29.7?months (±28.4) vs. 21.4?months (±18.1), respectively, p?=?7?×?10?4]. Only 27.8% of US participants indicated that their child diagnosed with ASD had undergone diagnostic genetic testing, whereas 61.7% of the French participants indicated this was the case (p?=?2.7?×?10?12). In both countries, the majority of respondents (69.3% and 80% from France and the US, respectively) indicated high interest in the use of a genetic screening test for autism. Conclusion: Parents from France and the US report a persistent delay between the initial suspicion of a difference in development and the diagnosis of ASD. Significantly fewer US participants underwent genetic testing although this result should be regarded as exploratory given the limitations. The significance of these between country differences will be discussed. PMID:24795872

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

    SciTech Connect

    Munne, S.; Cohen, J.; Grifo, J.

    1994-09-01

    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.

  8. The Ethical Implications of Preimplantation Genetic

    E-print Network

    Brutlag, Doug

    : PGD used to screen mutations for severe, irreversible, genetic conditions ­ Sickle-cell anemia ­ Tay-Sachs gene defects in autosomal disease ·Single gene defects in male infertility ·Identification of sex in X-linked diseases ·Aneuploidy screening in women of advanced maternal age ·Aneuploidy screening for male infertility

  9. Genetic Identification Is Critical for the Diagnosis of Parkinsonism: A Chinese Pedigree with Early Onset of Parkinsonism

    PubMed Central

    Yang, Yang; Tang, Bei-sha; Weng, Ling; Li, Nan; Shen, Lu; Wang, Jian; Zuo, Chuan-tao; Yan, Xin-xiang; Xia, Kun; Guo, Ji-feng

    2015-01-01

    Background A number of hereditary neurological diseases display indistinguishable features at the early disease stage. Parkinsonian symptoms can be found in numerous diseases, making it difficult to get a definitive early diagnosis of primary causes for patients with onset of parkinsonism. The accurate and early diagnosis of the causes of parkinsonian patients is important for effective treatments of these patients. Methods We have identified a Chinese family (82 family members over four generations with 21 affected individuals) that manifested the characterized symptoms of parkinsonism and was initially diagnosed as Parkinson’s disease. We followed up with the family for two years, during which we carried out clinical observations, Positron Emission Tomography-Computed Tomography neuroimaging analysis, and exome sequencing to correctly diagnose the case. Results During the two-year follow-up period, we performed comprehensive medical history collection, physical examination, and structural and functional neuroimaging studies of this Chinese family. We found that the patient exhibited progressive deteriorated parkinsonism with Parkinson disease-like neuropathology and also had a good response to the initial levodopa treatment. However, exome sequencing identified a missense mutation, N279K, in exon 10 of MAPT gene, verifying that the early parkinsonian symptoms in this family are caused by the genetic mutation for hereditary frontotemporal lobar dementia. Conclusions For the inherited parkinsonian patients who even show the neuropathology similar to that in Parkinson’s disease and have initial response to levodopa treatment, genetic identification of the molecular basis for the disease is still required for defining the early diagnosis and correct treatment. PMID:26295349

  10. The genetics of Charcot–Marie–Tooth disease: current trends and future implications for diagnosis and management

    PubMed Central

    Hoyle, J Chad; Isfort, Michael C; Roggenbuck, Jennifer; Arnold, W David

    2015-01-01

    Charcot–Marie–Tooth (CMT) disease is the most common hereditary polyneuropathy and is classically associated with an insidious onset of distal predominant motor and sensory loss, muscle wasting, and pes cavus. Other forms of hereditary neuropathy, including sensory predominant or motor predominant forms, are sometimes included in the general classification of CMT, but for the purpose of this review, we will focus primarily on the forms associated with both sensory and motor deficits. CMT has a great deal of genetic heterogeneity, leading to diagnostic considerations that are still rapidly evolving for this disorder. Clinical features, inheritance pattern, gene mutation frequencies, and electrodiagnostic features all are helpful in formulating targeted testing algorithms in practical clinical settings, but these still have shortcomings. Next-generation sequencing (NGS), combined with multigene testing panels, is increasing the sensitivity and efficiency of genetic testing and is quickly overtaking targeted testing strategies. Currently, multigene panel testing and NGS can be considered first-line in many circumstances, although obtaining initial targeted testing for the PMP22 duplication in CMT patients with demyelinating conduction velocities is still a reasonable strategy. As technology improves and cost continues to fall, targeted testing will be completely replaced by multigene NGS panels that can detect the full spectrum of CMT mutations. Nevertheless, clinical acumen is still necessary given the variants of uncertain significance encountered with NGS. Despite the current limitations, the genetic diagnosis of CMT is critical for accurate prognostication, genetic counseling, and in the future, specific targeted therapies. Although whole exome and whole genome sequencing strategies have the power to further elucidate the genetics of CMT, continued technological advances are needed. PMID:26527893

  11. Mosaic small supernumerary marker chromosome 1 at amniocentesis: prenatal diagnosis, molecular genetic analysis and literature review.

    PubMed

    Chen, Chih-Ping; Chen, Ming; Su, Yi-Ning; Huang, Jian-Pei; Chern, Schu-Rern; Wu, Peih-Shan; Su, Jun-Wei; Chang, Shun-Ping; Chen, Yu-Ting; Lee, Chen-Chi; Chen, Li-Feng; Pan, Chen-Wen; Wang, Wayseen

    2013-10-15

    We present prenatal diagnosis and molecular cytogenetic analysis of mosaic small supernumerary marker chromosome 1 [sSMC(1)]. We review the literature of sSMC(1) at amniocentesis and chromosome 1p21.1-p12 duplication syndrome. We discuss the genotype-phenotype correlation of the involved genes of ALX3, RBM15, NTNG1, SLC25A24, GPSM2, TBX15 and NOTCH2 in this case. PMID:23933412

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

    PubMed

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

    2014-10-01

    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 dmd.nl 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

  13. Counseling Challenges with Variants of Uncertain Significance and Incidental Findings in Prenatal Genetic Screening and Diagnosis

    PubMed Central

    Westerfield, Lauren; Darilek, Sandra; van den Veyver, Ignatia B.

    2014-01-01

    Prenatal genetic screening and testing provides prospective parents information about the health of their fetus. It is offered to find or address an increased risk for chromosomal abnormalities or other genetic conditions in the fetus or to identify the cause of fetal structural abnormalities detected by prenatal imaging. Genome-wide tests, such as the already widely-used chromosomal microarray analysis and emerging diagnostic whole exome and whole genome sequencing, have improved the ability to detect clinically significant findings, but have also increased the chance of detecting incidental findings and variants of uncertain significance. There is an extensive ongoing discussion about optimal strategies for diagnostic laboratories to report such findings and for providers to communicate them with patients. While consensus opinions and guidelines are beginning to appear, they often exclude the prenatal setting, due to its unique set of challenging considerations. These include more limited knowledge of the impact of genetic variants when prospectively detected in an ongoing pregnancy, the absence or limitations of detecting clinically recognizable phenotypes at the time of testing and the different decision-making processes that will ensue from testing. In this review, we examine these challenges within the medical ethical framework unique to prenatal care. PMID:26237491

  14. Accurate genetic diagnosis of Finnish pulmonary arterial hypertension patients using oligonucleotide-selective sequencing

    PubMed Central

    Vattulainen, Sanna; Aho, Joonas; Salmenperä, Pertteli; Bruce, Siina; Tallila, Jonna; Gentile, Massimiliano; Sankelo, Marja; Laitinen, Tarja; Koskenvuo, Juha W; Alastalo, Tero-Pekka; Myllykangas, Samuel

    2015-01-01

    The genetic basis of pulmonary arterial hypertension (PAH) among Finnish PAH patients is poorly understood. We adopted a novel-targeted next-generation sequencing (NGS) approach called Oligonucleotide-Selective Sequencing (OS-Seq) and developed a custom data analysis and interpretation pipeline to identify pathogenic base substitutions, insertions, and deletions in seven genes associated with PAH (BMPR2, BMPR1B, ACVRL1, ENG, SMAD9, CAV1, and KCNK3) from Finnish PAH patients. This study represents the first clinical study with OS-Seq technology on patients suffering from a rare genetic disorder. We analyzed DNA samples from 21 Finnish PAH patients, whose BMPR2 and ACVRL1 mutation status had been previously studied using Sanger sequencing. Our sequencing panel covered 100% of the targeted base pairs with >15× sequencing depth. Pathogenic base substitutions were identified in the BMPR2 gene in 29% of the Finnish PAH cases. Two of the pathogenic variant-positive patients had been previously tested negative using Sanger sequencing. No clinically significant variants were identified in the six other PAH genes. Our study validates the use of targeted OS-Seq for genetic diagnostics of PAH and revealed pathogenic variants that had been previously missed using Sanger sequencing. PMID:26247051

  15. At the intersection of toxicology, psychiatry, and genetics: a diagnosis of ornithine transcarbamylase deficiency.

    PubMed

    Sloas, Harold Andrew; Ence, Thomas C; Mendez, Donna R; Cruz, Andrea T

    2013-09-01

    Ornithine transcarbamylase (OTC) deficiency is a genetic disorder involving a mutation of the ornithine transcarbamylase gene, located on the short arm of the X chromosome (Xp21.1). This makes the expression of the gene most common in homozygous males, but heterozygous females can also be affected and may be more likely to suffer from serious morbidity. Most males present early in the neonatal period with more devastating outcomes than their female counterparts. Up to 34% will present in the first 30 days of life (J Pediatr 2001;138:S30). Females often have partially functioning mitochondria due to uneven distribution of the mutant gene secondary to lyonization (“X-chromosome Inactivation”. Genetics Home Reference, 2012). Occasionally, symptomatic females may not even present until they are placed under metabolic stress such as a severe illness, fasting, pregnancy, or new medication (Roth KS, Steiner RD. “Ornithine Transcarbamylase Deficiency”. EMedicine, 2012). The urea cycle is the body's primary tool for the disposal of excess nitrogen, which is generated by the routine metabolism of proteins and amino acids. Mitochondrial dysfunction impairs urea production and result in hyperammonemia (Semin Neonatol 2002;7:27). The sine qua non among all degrees of OTC deficiency at presentation is hyperammonemia. As in adults, children will have similar symptoms of encephalopathy, but this may be expressed differently depending on the child's developmental level. We present an unusual case of OTC deficiency in an older child with undifferentiated symptoms of an anticholinergic toxidrome, liver failure, iron overdose, and mushroom poisoning. PMID:23790482

  16. Role of genetics in diagnosis and therapy of acquired liver disease.

    PubMed

    Zimmer, Vincent; Lammert, Frank

    2014-06-01

    By implementation of novel genotyping technologies, progress in delineating the genetic architecture of acquired liver diseases has been achieved in recent years. The rapid dissemination of genome-wide linkage and association studies has paved the way for the identification of genetic variants that cause or modify non-viral liver diseases as well as the natural and treatment-related outcomes in chronic viral hepatitis. Invaluable genomic data has recently been derived from additional genome-wide association studies (GWAS) of the archetypical cholestatic liver diseases primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). Beyond providing novel pathobiological insights in need of more sophisticated functional annotation, gene variation might in the future be instrumental in precise risk stratification and the development of genotype-based treatment algorithms. In this regard, the definition of subtypes of acquired liver disease and re-categorization of clinically defined disease phenotypes into a more 'genometype'-based disease classification represents a priority future research direction. PMID:24405709

  17. Telethon Network of Genetic Biobanks: a key service for diagnosis and research on rare diseases.

    PubMed

    Filocamo, Mirella; Baldo, Chiara; Goldwurm, Stefano; Renieri, Alessandra; Angelini, Corrado; Moggio, Maurizio; Mora, Marina; Merla, Giuseppe; Politano, Luisa; Garavaglia, Barbara; Casareto, Lorena; Bricarelli, Francesca Dagna

    2013-01-01

    Several examples have always illustrated how access to large numbers of biospecimens and associated data plays a pivotal role in the identification of disease genes and the development of pharmaceuticals. Hence, allowing researchers to access to significant numbers of quality samples and data, genetic biobanks are a powerful tool in basic, translational and clinical research into rare diseases. Recently demand for well-annotated and properly-preserved specimens is growing at a high rate, and is expected to grow for years to come. The best effective solution to this issue is to enhance the potentialities of well-managed biobanks by building a network.Here we report a 5-year experience of the Telethon Network of Genetic Biobanks (TNGB), a non-profit association of Italian repositories created in 2008 to form a virtually unique catalogue of biospecimens and associated data, which presently lists more than 750 rare genetic defects. The process of TNGB harmonisation has been mainly achieved through the adoption of a unique, centrally coordinated, IT infrastructure, which has enabled (i) standardisation of all the TNGB procedures and activities; (ii) creation of an updated TNGB online catalogue, based on minimal data set and controlled terminologies; (iii) sample access policy managed via a shared request control panel at web portal. TNGB has been engaged in disseminating information on its services into both scientific/biomedical - national and international - contexts, as well as associations of patients and families. Indeed, during the last 5-years national and international scientists extensively used the TNGB with different purposes resulting in more than 250 scientific publications. In addition, since its inception the TNGB is an associated member of the Biobanking and Biomolecular Resources Research Infrastructure and recently joined the EuroBioBank network. Moreover, the involvement of patients and families, leading to the formalization of various agreements between TNGB and Patients' Associations, has demonstrated how promoting Biobank services can be instrumental in gaining a critical mass of samples essential for research, as well as, raising awareness, trust and interest of the general public in Biobanks. This article focuses on some fundamental aspects of networking and demonstrates how the translational research benefits from a sustained infrastructure. PMID:24004821

  18. Telethon Network of Genetic Biobanks: a key service for diagnosis and research on rare diseases

    PubMed Central

    2013-01-01

    Several examples have always illustrated how access to large numbers of biospecimens and associated data plays a pivotal role in the identification of disease genes and the development of pharmaceuticals. Hence, allowing researchers to access to significant numbers of quality samples and data, genetic biobanks are a powerful tool in basic, translational and clinical research into rare diseases. Recently demand for well-annotated and properly-preserved specimens is growing at a high rate, and is expected to grow for years to come. The best effective solution to this issue is to enhance the potentialities of well-managed biobanks by building a network. Here we report a 5-year experience of the Telethon Network of Genetic Biobanks (TNGB), a non-profit association of Italian repositories created in 2008 to form a virtually unique catalogue of biospecimens and associated data, which presently lists more than 750 rare genetic defects. The process of TNGB harmonisation has been mainly achieved through the adoption of a unique, centrally coordinated, IT infrastructure, which has enabled (i) standardisation of all the TNGB procedures and activities; (ii) creation of an updated TNGB online catalogue, based on minimal data set and controlled terminologies; (iii) sample access policy managed via a shared request control panel at web portal. TNGB has been engaged in disseminating information on its services into both scientific/biomedical - national and international - contexts, as well as associations of patients and families. Indeed, during the last 5-years national and international scientists extensively used the TNGB with different purposes resulting in more than 250 scientific publications. In addition, since its inception the TNGB is an associated member of the Biobanking and Biomolecular Resources Research Infrastructure and recently joined the EuroBioBank network. Moreover, the involvement of patients and families, leading to the formalization of various agreements between TNGB and Patients’ Associations, has demonstrated how promoting Biobank services can be instrumental in gaining a critical mass of samples essential for research, as well as, raising awareness, trust and interest of the general public in Biobanks. This article focuses on some fundamental aspects of networking and demonstrates how the translational research benefits from a sustained infrastructure. PMID:24004821

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

    PubMed Central

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

    1996-01-01

    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

  20. The molecular genetic basis and diagnosis of familial hypercholesterolemia in Denmark.

    PubMed

    Jensen, Henrik Kjoerulf

    2002-11-01

    Normal function of the hepatic low-density lipoprotein (LDL) receptor is obligate for normal levels of plasma LDL cholesterol. The LDL receptor regulates the concentration of plasma LDL cholesterol by internalizing apolipoprotein B-100- and apolipoprotein E-containing lipoproteins by receptor-mediated endocytosis. Mutations in the gene encoding the LDL receptor protein give rise to one of the most common classical autosomal dominant inherited disorders in man, familial hypercholesterolemia (FH). The estimated prevalence of heterozygous FH is 0.2% (1:500) in most populations of the world including the Danish. Worldwide, an estimated ten million people are afflicted with FH and in Denmark there are approximately 10,000 subjects with heterozygous FH. Persons with heterozygous FH are characterized by a severely elevated concentration of LDL cholesterol in plasma starting in early childhood, tendon xanthomas and a markedly increased risk of premature coronary heart disease (CHD). Adequate control of plasma LDL cholesterol levels can be achieved in most patients with heterozygous FH, and to a lesser extent in the very rare cases with homozygous FH, using combinations of diet, drug therapy and selective LDL-apheresis. So, it is very important that physicians be aware of this relatively common disorder since there is good evidence that early diagnosis and cholesterol-lowering therapy will delay or even prevent CHD in persons with FH. A large majority of these persons, however, are still not diagnosed or adequately treated. It is believed that the diagnostic abilities molecular biology has to offer will provide the impetus for correcting this situation. The aims of the studies behind the present thesis, therefore, were to obtain important knowledge about current mutation detection technology, prevalence and spectrum of LDL receptor gene mutations in Denmark, methods to evaluate pathogenicity of LDL receptor gene mutations, relationship between FH genotype-phenotype, and clinical versus DNA diagnosis in the Danish FH population. Among different relative laborious and expensive scanning methods for unknown gene mutations we have shown that the polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) analysis is a highly efficient and sensitive technique for detection of mutations in the 18 exons including intronic splice-site sequences and the promoter region of the LDL receptor gene, reserving DNA sequencing to the exons revealing variant SSCP patterns. Southern blot analysis or long distance PCR analysis are necessary to identify large gene re-arrangements in the LDL receptor gene in FH patients in whom SSCP analysis did not reveal any smaller sequence alterations. Worldwide, about 700 different mutations in the LDL receptor gene have been reported and in the Danish FH population we have so far identified 60 different mutations localized throughout the LDL receptor gene. In certain populations a small number of mutations predominate due to founder effects. The spectrum of LDL receptor mutations in Danish FH patients is intermediate between such specific founder populations with 5 predominant mutations (W23X, W66G, W556S, 313 + 1G-->A, 1846-1G-->A) accounting for about 40-50% of FH. These frequent mutations can easily and inexpensively be tested for by specific PCR based assays using restriction enzyme cleavage. Future analysis of LDL receptor mutations in heterozygous FH subjects, therefore, should be based on the mutational spectrum present in each relevant specific subset. Most mutations in the LDL receptor gene cause the classical heterozygous form of FH, but a small proportion seem to result in mild or moderate forms of autosomal, dominantly inherited hypercholesterolemia. Differentiation between harmless sequence variations and disease-causing mutations is not always easy without additional work. We have experienced that large re-arrangements, frame-shift and nonsense mutations obviously are pathogenic, but full pathogenicity should not be ascribed to missense mutations and small in-frame deletion

  1. Characterization and noninvasive diagnosis of bladder cancer with serum surface enhanced Raman spectroscopy and genetic algorithms

    NASA Astrophysics Data System (ADS)

    Li, Shaoxin; Li, Linfang; Zeng, Qiuyao; Zhang, Yanjiao; Guo, Zhouyi; Liu, Zhiming; Jin, Mei; Su, Chengkang; Lin, Lin; Xu, Junfa; Liu, Songhao

    2015-05-01

    This study aims to characterize and classify serum surface-enhanced Raman spectroscopy (SERS) spectra between bladder cancer patients and normal volunteers by genetic algorithms (GAs) combined with linear discriminate analysis (LDA). Two group serum SERS spectra excited with nanoparticles are collected from healthy volunteers (n = 36) and bladder cancer patients (n = 55). Six diagnostic Raman bands in the regions of 481-486, 682-687, 1018-1034, 1313-1323, 1450-1459 and 1582-1587 cm-1 related to proteins, nucleic acids and lipids are picked out with the GAs and LDA. By the diagnostic models built with the identified six Raman bands, the improved diagnostic sensitivity of 90.9% and specificity of 100% were acquired for classifying bladder cancer patients from normal serum SERS spectra. The results are superior to the sensitivity of 74.6% and specificity of 97.2% obtained with principal component analysis by the same serum SERS spectra dataset. Receiver operating characteristic (ROC) curves further confirmed the efficiency of diagnostic algorithm based on GA-LDA technique. This exploratory work demonstrates that the serum SERS associated with GA-LDA technique has enormous potential to characterize and non-invasively detect bladder cancer through peripheral blood.

  2. Characterization and noninvasive diagnosis of bladder cancer with serum surface enhanced Raman spectroscopy and genetic algorithms

    PubMed Central

    Li, Shaoxin; Li, Linfang; Zeng, Qiuyao; Zhang, Yanjiao; Guo, Zhouyi; Liu, Zhiming; Jin, Mei; Su, Chengkang; Lin, Lin; Xu, Junfa; Liu, Songhao

    2015-01-01

    This study aims to characterize and classify serum surface-enhanced Raman spectroscopy (SERS) spectra between bladder cancer patients and normal volunteers by genetic algorithms (GAs) combined with linear discriminate analysis (LDA). Two group serum SERS spectra excited with nanoparticles are collected from healthy volunteers (n = 36) and bladder cancer patients (n = 55). Six diagnostic Raman bands in the regions of 481–486, 682–687, 1018–1034, 1313–1323, 1450–1459 and 1582–1587 cm?1 related to proteins, nucleic acids and lipids are picked out with the GAs and LDA. By the diagnostic models built with the identified six Raman bands, the improved diagnostic sensitivity of 90.9% and specificity of 100% were acquired for classifying bladder cancer patients from normal serum SERS spectra. The results are superior to the sensitivity of 74.6% and specificity of 97.2% obtained with principal component analysis by the same serum SERS spectra dataset. Receiver operating characteristic (ROC) curves further confirmed the efficiency of diagnostic algorithm based on GA-LDA technique. This exploratory work demonstrates that the serum SERS associated with GA-LDA technique has enormous potential to characterize and non-invasively detect bladder cancer through peripheral blood. PMID:25947114

  3. Integrative functional genetic-epigenetic approach for selecting genes as urine biomarkers for bladder cancer diagnosis.

    PubMed

    Eissa, Sanaa; Matboli, Marwa; Essawy, Nada O E; Kotb, Youssef M

    2015-12-01

    Early screening for bladder cancer (BC) holds the key to combat and control the increasing global burden of BC mortality. We presented a simple approach to characterize, analyze, and validate a panel of biomarkers in BC and their relationship to bilharziasis. We investigated voided urine and blood samples from patients with bladder cancer (n?=?94), benign bladder lesions (n?=?60), and age-matched normal controls (n?=?56). This study was divided into the following phases. (1) We analyzed the expression of urinary Hyaluronoglucosaminidase 1 (HYAL1) protein in BC and control samples by zymography. (2) We performed bioinformatics analysis to retrieve a set of epigenetic regulators of HYAL1. (3) This set of three selected genes [long non-coding RNA-urothelial cancer associated 1(lncRNA-UCA1), microRNA-210, and microRNA-96] was then analyzed in the same urine samples used in phase I by quantitative real-time PCR. (4) A high reproducibility of gene selection results was also determined from statistical validation. The urinary expression of HYAL1 protein and its epigenetic regulators were higher in BC patients (P?diagnosis. PMID:26138586

  4. Genetics

    MedlinePLUS

    Homozygous; Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

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

    NASA Astrophysics Data System (ADS)

    Meju, Maxwell A.

    2000-05-01

    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.

  6. Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data

    PubMed Central

    Wright, Caroline F; Fitzgerald, Tomas W; Jones, Wendy D; Clayton, Stephen; McRae, Jeremy F; van Kogelenberg, Margriet; King, Daniel A; Ambridge, Kirsty; Barrett, Daniel M; Bayzetinova, Tanya; Bevan, A Paul; Bragin, Eugene; Chatzimichali, Eleni A; Gribble, Susan; Jones, Philip; Krishnappa, Netravathi; Mason, Laura E; Miller, Ray; Morley, Katherine I; Parthiban, Vijaya; Prigmore, Elena; Rajan, Diana; Sifrim, Alejandro; Swaminathan, G Jawahar; Tivey, Adrian R; Middleton, Anna; Parker, Michael; Carter, Nigel P; Barrett, Jeffrey C; Hurles, Matthew E; FitzPatrick, David R; Firth, Helen V

    2015-01-01

    Summary Background Human genome sequencing has transformed our understanding of genomic variation and its relevance to health and disease, and is now starting to enter clinical practice for the diagnosis of rare diseases. The question of whether and how some categories of genomic findings should be shared with individual research participants is currently a topic of international debate, and development of robust analytical workflows to identify and communicate clinically relevant variants is paramount. Methods The Deciphering Developmental Disorders (DDD) study has developed a UK-wide patient recruitment network involving over 180 clinicians across all 24 regional genetics services, and has performed genome-wide microarray and whole exome sequencing on children with undiagnosed developmental disorders and their parents. After data analysis, pertinent genomic variants were returned to individual research participants via their local clinical genetics team. Findings Around 80?000 genomic variants were identified from exome sequencing and microarray analysis in each individual, of which on average 400 were rare and predicted to be protein altering. By focusing only on de novo and segregating variants in known developmental disorder genes, we achieved a diagnostic yield of 27% among 1133 previously investigated yet undiagnosed children with developmental disorders, whilst minimising incidental findings. In families with developmentally normal parents, whole exome sequencing of the child and both parents resulted in a 10-fold reduction in the number of potential causal variants that needed clinical evaluation compared to sequencing only the child. Most diagnostic variants identified in known genes were novel and not present in current databases of known disease variation. Interpretation Implementation of a robust translational genomics workflow is achievable within a large-scale rare disease research study to allow feedback of potentially diagnostic findings to clinicians and research participants. Systematic recording of relevant clinical data, curation of a gene–phenotype knowledge base, and development of clinical decision support software are needed in addition to automated exclusion of almost all variants, which is crucial for scalable prioritisation and review of possible diagnostic variants. However, the resource requirements of development and maintenance of a clinical reporting system within a research setting are substantial. Funding Health Innovation Challenge Fund, a parallel funding partnership between the Wellcome Trust and the UK Department of Health. PMID:25529582

  7. Functional testing strategy for coding genetic variants of unclear significance in MLH1 in Lynch syndrome diagnosis.

    PubMed

    Hinrichsen, Inga; Schäfer, Dieter; Langer, Deborah; Köger, Nicole; Wittmann, Margarethe; Aretz, Stefan; Steinke, Verena; Holzapfel, Stefanie; Trojan, Jörg; König, Rainer; Zeuzem, Stefan; Brieger, Angela; Plotz, Guido

    2015-02-01

    Lynch syndrome is caused by inactivating mutations in the MLH1 gene, but genetic variants of unclear significance frequently preclude diagnosis. Functional testing can reveal variant-conferred defects in gene or protein function. Based on functional defect frequencies and clinical applicability of test systems, we developed a functional testing strategy aimed at efficiently detecting pathogenic defects in coding MLH1 variants. In this strategy, tests of repair activity and expression are prioritized over analyses of subcellular protein localization and messenger RNA (mRNA) formation. This strategy was used for four unclear coding MLH1 variants (p.Asp41His, p.Leu507Phe, p.Gln689Arg, p.Glu605del + p.Val716Met). Expression was analyzed using a transfection system, mismatch repair (MMR) activity by complementation in vitro, mRNA formation by reverse transcriptase-PCR in carrier lymphocyte mRNA, and subcellular localization with dye-labeled fusion constructs. All tests included clinically meaningful controls. The strategy enabled efficient identification of defects in two unclear variants: the p.Asp41His variant showed loss of MMR activity, whereas the compound variant p.Glu605del + p.Val716Met had a defect of expression. This expression defect was significantly stronger than the pathogenic expression reference variant analyzed in parallel, therefore the defect of the compound variant is also pathogenic. Interestingly, the expression defect was caused additively by both of the compound variants, at least one of which is non-pathogenic when occurring by itself. Tests were neutral for p.Leu507Phe and p.Gln689Arg, and the results were consistent with available clinical data. We finally discuss the improved sensitivity and efficiency of the applied strategy and its limitations in analyzing unclear coding MLH1 variants. PMID:25477341

  8. Medical genetics

    SciTech Connect

    Jorde, L.B.; Carey, J.C.; White, R.L.

    1995-10-01

    This book on the subject of medical genetics is a textbook aimed at a very broad audience: principally, medical students, nursing students, graduate, and undergraduate students. The book is actually a primer of general genetics as applied to humans and provides a well-balanced introduction to the scientific and clinical basis of human genetics. The twelve chapters include: Introduction, Basic Cell Biology, Genetic Variation, Autosomal Dominant and Recessive Inheritance, Sex-linked and Mitochondrial Inheritance, Clinical Cytogenetics, Gene Mapping, Immunogenetics, Cancer Genetics, Multifactorial Inheritance and Common Disease, Genetic Screening, Genetic Diagnosis and Gene Therapy, and Clinical Genetics and Genetic Counseling.

  9. Molecular Genetic Diagnosis of a Bethlem Myopathy Family with an Autosomal-Dominant COL6A1 Mutation, as Evidenced by Exome Sequencing

    PubMed Central

    Park, Hyung Jun; Choi, Young-Chul; Kim, Seung Min; Kim, Se Hoon; Hong, Young Bin; Yoon, Bo Ram

    2015-01-01

    Background We describe herein the application of whole exome sequencing (WES) for the molecular genetic diagnosis of a large Korean family with dominantly inherited myopathy. Case Report The affected individuals presented with slowly progressive proximal weakness and ankle contracture. They were initially diagnosed with limb-girdle muscular dystrophy (LGMD) based on clinical and pathologic features. However, WES and subsequent capillary sequencing identified a pathogenic splicing-site mutation (c.1056+1G>A) in COL6A1, which was previously reported to be an underlying cause of Bethlem myopathy. After identification of the genetic cause of the disease, careful neurologic examination revealed subtle contracture of the interphalangeal joint in the affected members, which is a characteristic sign of Bethlem myopathy. Therefore, we revised the original diagnosis from LGMD to Bethlem myopathy. Conclusions This is the first report of identification of COL6A1-mediated Bethlem myopathy in Korea, and indicates the utility of WES for the diagnosis of muscular dystrophy. PMID:25749816

  10. Single strand conformation polymorphism analysis of androgen receptor gene mutations in patients with androgen insensitivity syndromes: Application for diagnosis, genetic counseling, and therapy

    SciTech Connect

    Hiort, O. Tufts-New England Medical Center, Boston, MA ); Huang, Q. ); Sinnecker, G.H.G.; Kruse, K. ); Sadeghi-Nejad, A.; Wolfe, H.J. ); Yandell, D.W. ) Harvard School of Public Health, Boston, MA )

    1993-07-01

    Recent studies indicate that mutations in the androgen receptor gene are associated with androgen insensitivity syndromes, a heterogeneous group of related disorders involving defective sexual differentiation in karyotypic males. In this report, the authors address the possibility of rapid mutational analysis of the androgen receptor gene for initial diagnosis, genetic counseling, and molecular subclassification of affected patients and their families. DNA from peripheral blood leukocytes of six patients from five families with various degrees of androgen insensitivity was studied. Exons 2 to 8 of the androgen receptor gene were analyzed using a combination of single strand conformation polymorphism analysis and direct DNA sequencing. Female family members were also studied to identify heterozygote carriers. Point mutations in the AR gene were identified in all six patients, and all mutations caused amino acid substitutions. One patient with incomplete androgen insensitivity was a mosaic for the mutation. Four of the five mothers, as well as a young sister of one patient, were carriers of the mutation present in the affected child. The data show that new mutations may occur in the androgen receptor gene leading to sporadic androgen insensitivity syndrome. Molecular genetic characterization of the variant allele can serve as a primary tool for diagnosis and subsequent therapy, and can provide a basis for distinguishing heterozygous carriers in familial androgen resistance. The identification of carriers is of substantial clinical importance for genetic counseling. 29 refs., 2 figs., 1 tab.

  11. 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

    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

    2014-01-01

    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

  12. 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

    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

    2014-01-01

    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

  13. Concurrent visual diagnosis and susceptibility profiling of the first line drug against visceral leishmaniasis by plasmonic detection of PCR amplified genetic biomarker.

    PubMed

    Bose, Partha Pratim; Kumar, Prakash; Munagala, Narendar

    2015-12-01

    Visceral form of leishmaniasis (also known as Kala-azar) is a fatal neglected tropical disease affecting 95 countries worldwide. Recently, substantial proportion of resistance related treatment failure cases have been reported against its first line drug, sodium-antimony gluconate (SAG). We report an easy, fast, sensitive and cheap visual diagnosis and SAG susceptibility profiling for this disease based on recently recognized genetic biomarker and gold nanoparticle based plasmonic detection phenomenon. This is a non-gel, non-culture based detection technique, which can be used as simultaneous high throughput detection and SAG-susceptibility profiling in Leishmania endemic resource stringent countries. PMID:26394185

  14. Presentation of Progressive Familial Intrahepatic Cholestasis Type 3 Mimicking Wilson Disease: Molecular Genetic Diagnosis and Response to Treatment

    PubMed Central

    Jain, Dhanpat; Schilsky, Michael L.

    2015-01-01

    Progressive familial intrahepatic cholestasis type 3 (PFIC3) is an autosomal recessive disorder of cholestasis of hepatocellular origin, typically seen in infancy or childhood caused by a defect in the ABCB4 located on chromosome 7. Here we report on an older patient, aged 15, who presented with biochemical testing that led to an initial consideration of a diagnosis of Wilson disease (WD) resulting in a delayed diagnosis of PFIC3. Diagnosis of PFIC3 was later confirmed by molecular studies that identified novel mutations in the ABCB4 gene. Cholestasis due to PFIC3 can cause elevated hepatic copper and increased urine copper excretion that overlap with current diagnostic criteria for WD. Molecular diagnostics are very useful for establishing the diagnosis of PFIC3. Ursodeoxycholic acid ameliorates cholestasis in PFIC3, and may help mediate a reduction in hepatic copper content in response to treatment. PMID:26473142

  15. Genetic technology: Promises and problems

    NASA Technical Reports Server (NTRS)

    Frankel, M. S.

    1975-01-01

    Issues concerning the use of genetic technology are discussed. Some areas discussed include treating genetic disease, prenatal diagnosis and selective abortion, screening for genetic disease, and genetic counseling. Policy issues stemming from these capabilities are considered.

  16. European guidance for the molecular diagnosis of pseudohypoparathyroidism not caused by point genetic variants at GNAS: an EQA study.

    PubMed

    Garin, Intza; Mantovani, Giovanna; Aguirre, Urko; Barlier, Anne; Brix, Bettina; Elli, Francesca M; Freson, Kathleen; Grybek, Virginie; Izzi, Benedetta; Linglart, Agnès; Perez de Nanclares, Guiomar; Silve, Caroline; Thiele, Susanne; Werner, Ralf

    2015-04-01

    Pseudohypoparathyroidism is a rare endocrine disorder that can be caused by genetic (mainly maternally inherited inactivating point mutations, although intragenic and gross deletions have rarely been reported) or epigenetic alterations at GNAS locus. Clinical and molecular characterization of this disease is not that easy because of phenotypic, biochemical and molecular overlapping features between both subtypes of the disease. The European Consortium for the study of PHP (EuroPHP) designed the present work with the intention of generating the standards of diagnostic clinical molecular (epi)genetic testing in PHP patients. With this aim, DNA samples of eight independent PHP patients carrying GNAS genetic and/or epigenetic defects (three patients with GNAS deletions, two with 20q uniparental disomy and three with a methylation defect of unknown origin) without GNAS point mutations were anonymized and sent to the five participant laboratories for their routine genetic analysis (methylation-specific (MS)-MLPA, pyrosequencing and EpiTYPER) and interpretations. All laboratories were able to detect methylation defects and, after the data analysis, the Consortium compared the results to define technical advantages and disadvantages of different techniques. To conclude, we propose as first-level investigation in PHP patients copy number and methylation analysis by MS-MLPA. Then, in patients with partial methylation defect, the result should be confirmed by single CpG bisulphite-based methods (ie pyrosequencing), whereas in case of a complete methylation defect without detectable deletion, microsatellites or SNP genotyping should be performed to exclude uniparental disomy 20. PMID:25005735

  17. Autism Spectrum Disorders in Genetic Syndromes: Implications for Diagnosis, Intervention and Understanding the Wider Autism Spectrum Disorder Population

    ERIC Educational Resources Information Center

    Moss, J.; Howlin, P.

    2009-01-01

    Background: An emerging literature on behavioural phenotypes has highlighted apparent associations between autism spectrum disorders (ASDs) or ASD-related phenomenology and a number of different genetically determined syndromes. Method: A systematic review of the current literature regarding the association with ASD and ASD characteristics was…

  18. A Family Perspective of the Value of a Diagnosis for Intellectual Disability: Experiences from a Genetic Research Study

    ERIC Educational Resources Information Center

    Statham, Helen; Ponder, Maggie; Richards, Martin; Hallowell, Nina; Raymond, Frances Lucy

    2011-01-01

    Many professionals working with individuals with intellectual disability are unconcerned with why someone has the impairment. Genetic aspects may be viewed as, at best irrelevant, but more often, potentially negative. However, where the intellectual disability may be inherited, there are implications for family members and the individual. The data…

  19. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

  20. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maintaining genetic variation in wild populations of Arctic organisms is fundamental to the long-term persistence of high latitude biodiversity. Variability is important because it provides options for species to respond to changing environmental conditions and novel challenges such as emerging path...

  1. Quantitative analysis of methylation status at 11p15 and 7q21 for the genetic diagnosis of Beckwith-Wiedemann syndrome and Silver-Russell syndrome.

    PubMed

    Lee, Beom Hee; Kim, Gu-Hwan; Oh, Tae Jeong; Kim, Joo Hyun; Lee, Jin-Joo; Choi, Seung Hoon; Lee, Joo Yeon; Kim, Jae-Min; Choi, In Hee; Kim, Yoo-Mi; Choi, Jin-Ho; Yoo, Han-Wook

    2013-09-01

    Methylation-specific (MS) multiplex ligation-dependent probe amplification (MLPA) at two differentially methylated regions (DMRs) at chromosome 11p15, H19-DMR and LIT1-DMR, and microsatellite analysis for uniparental disomy (UPD) at chromosome 7 or 11, have been recommended for the genetic diagnosis of the Beckwith-Wiedemann syndrome (BWS) and the Silver-Russell syndrome (SRS). In this study, the efficacy of the MS pyrosequencing method at H19-DMR and LIT1-DMR at 11p15 and SGCE-DMR at 7q21 was evaluated for the genetic diagnosis of BWS (n=18) and SRS (n=20) patients. Epigenetic alterations or UPD were detected in 83% of BWS and 50% of SRS individuals by MS-MLPA, but the detection rate increased to 95% of BWS and 70% of SRS by MS pyrosequencing. Thirteen BWS patients (72%) harbored loss-of-methylation (LOM) at LIT1-DMR and two patients (11%) harbored gain-of-methylation (GOM) at H19-DMR, whereas two patients (11%) had both LOM at LIT1-DMR and GOM at H19-DMR, reflecting paternal UPD 11. Thirteen SRS patients (65%) harbored LOM at H19-DMR, whereas one patient (5%) had GOM at SGCE-DMR, reflecting maternal UPD 7. Birth anthropometric profiles were significantly correlated to methylation scores at either H19-DMR or LIT1-DMR. In conclusion, MS pyrosequencing enhanced the detection rate of molecular defects in BWS and SRS. Moreover, it indicates that methylation status at 11p15.5 might have an important role in fetal growth. PMID:23803580

  2. Mediterranean Founder Mutation Database (MFMD): Taking Advantage from Founder Mutations in Genetics Diagnosis, Genetic Diversity and Migration History of the Mediterranean Population.

    PubMed

    Charoute, Hicham; Bakhchane, Amina; Benrahma, Houda; Romdhane, Lilia; Gabi, Khalid; Rouba, Hassan; Fakiri, Malika; Abdelhak, Sonia; Lenaers, Guy; Barakat, Abdelhamid

    2015-11-01

    The Mediterranean basin has been the theater of migration crossroads followed by settlement of several societies and cultures in prehistoric and historical times, with important consequences on genetic and genomic determinisms. Here, we present the Mediterranean Founder Mutation Database (MFMD), established to offer web-based access to founder mutation information in the Mediterranean population. Mutation data were collected from the literature and other online resources and systematically reviewed and assembled into this database. The information provided for each founder mutation includes DNA change, amino-acid change, mutation type and mutation effect, as well as mutation frequency and coalescence time when available. Currently, the database contains 383 founder mutations found in 210 genes related to 219 diseases. We believe that MFMD will help scientists and physicians to design more rapid and less expensive genetic diagnostic tests. Moreover, the coalescence time of founder mutations gives an overview about the migration history of the Mediterranean population. MFMD can be publicly accessed from http://mfmd.pasteur.ma. PMID:26173767

  3. Barren promise : the hope and heartache in treating infertility

    E-print Network

    McDonough, Maureen (Maureen Ann)

    2005-01-01

    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 ...

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

    PubMed Central

    2014-01-01

    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

  5. A comprehensive genetic diagnosis of Chinese muscular dystrophy and congenital myopathy patients by targeted next-generation sequencing.

    PubMed

    Dai, Yi; Wei, Xiaoming; Zhao, Yanhuan; Ren, Haitao; Lan, Zhangzhang; Yang, Yun; Chen, Lin; Cui, Liying

    2015-08-01

    Muscular dystrophies and congenital myopathies are a large group of heterogeneous inherited muscle disorders. The spectrum of muscular dystrophies and congenital myopathies extends to more than 50 diseases today, even excluding the common forms Duchenne Muscular Dystrophy, Myotonic Dystrophy and Facioscapulohumeral Dystrophy. Unfortunately, even by critical clinical evaluation and muscle pathology, diagnosis is still difficult. To potentially remediate this difficulty, we applied a microarray-based targeted next-generation sequencing (NGS) technology to diagnose these patients. There were 55 consecutive unrelated patients who underwent the test, 36 of which (65%) were found to have a causative mutation. Our result shows the accuracy and efficiency of next-generation sequencing in clinical circumstances and reflects the features and relative distribution of inherited myopathies in the Chinese population. PMID:25987458

  6. 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?

    PubMed

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

    2014-10-01

    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. PMID:24989832

  7. 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?

    PubMed Central

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

    2015-01-01

    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. vs. Myriad Genetics, Inc., et al., the United States 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. PMID:24989832

  8. Utility of immunohistochemical investigation of SDHB and molecular genetic analysis of SDH genes in the differential diagnosis of mesenchymal tumors of GIT.

    PubMed

    Dubova, M; Sedivcova, M; Michal, M; Kokoskova, B; Ryska, A; Smid, D; Daum, O

    2015-02-01

    Loss of expression of beta subunit of succinate dehydrogenase (SDHB) was proved to be present in a subgroup of KIT/PDGFRA wt gastrointestinal stromal tumors (GISTs). To evaluate possible diagnostic utility of SDHB immunohistochemistry in the differential diagnostics of mesenchymal tumors of gastrointestinal tract (GIT), 11 cases of KIT/PDGFRA wt GISTs, 12 gastric schwannomas (GSs), 20 solitary fibrous tumors (SFTs), 4 leiomyomas (LMs), 16 leiomyosarcomas (LMSs), 5 synovial sarcomas (SSs), 3 endometrioid stromal sarcomas (ESSs), and 1 ileal inflammatory myofibroblastic tumor (IMT) were investigated for SDHB immunoexpression together with molecular genetic analysis of genes encoding succinate dehydrogenase (SDH). Three recent cases of KIT/PDGFRA mutant GISTs were used as controls. Among the 11 KIT/PDGFRA wt GISTs, 6 expressed SDHB, 1 of them harboring a sequence change of SDHD. All SDHB-negative cases were SDHB-D wt. In 1 of the control GIST cases molecular genetic analysis revealed an SDHD sequence change in addition to a mutation in KIT exon 11. No SFT was truly SDHB-negative, but in 2 of them the staining was impossible to analyze. Furthermore, 1 SFT carried an SDHB and another 1 SDHD sequence change. All GSs, LMs, LMSs, SSs, ESSs, and IMT were SDHB-positive or non-analyzable, and SDHB-D wt. Additional factors may play a role in regulating expression of SDHB. Furthermore, SDHB immunohistochemistry alone may be misleading in excluding tumors other than GIST (especially SFT) in the differential diagnosis of KIT/PDGFRA wt mesenchymal tumors of GIT. PMID:25205505

  9. Genetics Home Reference: SADDAN

    MedlinePLUS

    ... might also find information on the diagnosis or management of SADDAN in Educational resources and Patient support . General information about the diagnosis and management of genetic conditions is available in the Handbook. ...

  10. Genetics Home Reference: Sialuria

    MedlinePLUS

    ... might also find information on the diagnosis or management of sialuria in Educational resources and Patient support . General information about the diagnosis and management of genetic conditions is available in the Handbook. ...

  11. Genetics Home Reference: Glycine encephalopathy

    MedlinePLUS

    ... Testing Registry Genetic testing PubMed Recent literature OMIM Genetic disorder catalog Conditions > Glycine encephalopathy On this page: Description Genetic changes Inheritance Diagnosis Additional information Other names Glossary definitions Reviewed April ...

  12. Genetics Home Reference: Hereditary pancreatitis

    MedlinePLUS

    ... Recent literature OMIM Genetic disorder catalog Conditions > Hereditary pancreatitis On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed October 2012 What is hereditary pancreatitis? Hereditary pancreatitis is a genetic condition characterized by ...

  13. Genetics Home Reference: Apert syndrome

    MedlinePLUS

    ... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Apert syndrome On this page: Description Genetic changes Inheritance Diagnosis ... names Glossary definitions Reviewed February 2008 What is Apert syndrome? Apert syndrome is a genetic disorder characterized by ...

  14. Genetics Home Reference: Northern epilepsy

    MedlinePLUS

    ... 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 ...

  15. Genetics Home Reference: Neuroblastoma

    MedlinePLUS

    ... 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 ...

  16. Anaphylactic- and calcium-dependent generation of prostaglandin D2 (PGD2), thromboxane B2, and other cyclooxygenase products of arachidonic acid by dispersed human lung cells and relationship to histamine release.

    PubMed

    Holgate, S T; Burns, G B; Robinson, C; Church, M K

    1984-10-01

    Proteolytic digestion of human lung tissue dispersed a population of cells (HDLC) containing 1 to 8% mast cells but which were free from bronchial and vascular smooth muscle. Incubation of HDLC with anti-human IgE, which released a net 24.8 + 4.3% of mast cell-derived histamine, stimulated a 14-fold increase in the generation of PGD2, a seven-fold increase in TXB2, and less than a twofold increase in PGF2 alpha, immunoreactive PGE, (i-PGE) and 6-keto-PGF1 alpha. A similar profile of prostanoid release was observed when cells were challenged with epsilon-specific anti-IgE, indicating that the response was specific to the coupling of IgE Fc receptors. The calcium ionophore A23187 also released prostanoids from HDLC in approximately the same proportions as anti-IgE. This stimulus, however, released only 50% as much PGD2 per nanogram histamine than did IgE-dependent activation, thereby showing a fundamental difference in the mechanisms by which the two agents activate mast cells and liberate arachidonic acid for oxidative metabolism. In concentration-response and time course experiments, both secretory stimuli released prostanoids and histamine in parallel. After separation of lung cells by isopyknic centrifugation, challenge with anti-IgE or A23187 released PGD2 only from those fractions containing mast cells, the amount released corresponding closely to both the mast cell concentration and net histamine release. On pooling data from all experiments, the closest correlation was found between release of PGD2 and histamine when cells were stimulated with either anti-IgE (r = 0.813, p less than 0.001) or A23187 (r = 0.763, p less than 0.001), supporting a mast cell origin for PGD2. The release of other prostanoids in fractions not containing mast cells demonstrates that macrophages, monocytes, and lymphocytes have the capacity to generate TXB2, PGF2 alpha, and i-PGE both in the absence and presence of mast cells. Thus, although mast cells are likely to be the major source of PGD2 generated upon IgE-dependent stimulation of HDLC, other cells dispersed from lung tissue have the capacity to generate prostanoids directly after activation of their IgE-Fc receptors and, indirectly after the secretion of mast cell mediators. PMID:6206153

  17. The Future of Prenatal Diagnosis and Screening

    PubMed Central

    Pergament, Eugene

    2014-01-01

    The future of prenatal diagnosis and screening lies in developing clinical approaches and laboratory technologies applicable to genetic analyses and therapeutic interventions during embryonic development. PMID:26237604

  18. Scabies Diagnosis

    MedlinePLUS

    ... CDC.gov . 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 ...

  19. Importance of Genetic Diversity Assessment in Crop Plants and Its Recent Advances: An Overview of Its Analytical Perspectives

    PubMed Central

    Govindaraj, M.; Vetriventhan, M.; Srinivasan, M.

    2015-01-01

    The importance of plant genetic diversity (PGD) is now being recognized as a specific area since exploding population with urbanization and decreasing cultivable lands are the critical factors contributing to food insecurity in developing world. Agricultural scientists realized that PGD can be captured and stored in the form of plant genetic resources (PGR) such as gene bank, DNA library, and so forth, in the biorepository which preserve genetic material for long period. However, conserved PGR must be utilized for crop improvement in order to meet future global challenges in relation to food and nutritional security. This paper comprehensively reviews four important areas; (i) the significance of plant genetic diversity (PGD) and PGR especially on agriculturally important crops (mostly field crops); (ii) risk associated with narrowing the genetic base of current commercial cultivars and climate change; (iii) analysis of existing PGD analytical methods in pregenomic and genomic era; and (iv) modern tools available for PGD analysis in postgenomic era. This discussion benefits the plant scientist community in order to use the new methods and technology for better and rapid assessment, for utilization of germplasm from gene banks to their applied breeding programs. With the advent of new biotechnological techniques, this process of genetic manipulation is now being accelerated and carried out with more precision (neglecting environmental effects) and fast-track manner than the classical breeding techniques. It is also to note that gene banks look into several issues in order to improve levels of germplasm distribution and its utilization, duplication of plant identity, and access to database, for prebreeding activities. Since plant breeding research and cultivar development are integral components of improving food production, therefore, availability of and access to diverse genetic sources will ensure that the global food production network becomes more sustainable. The pros and cons of the basic and advanced statistical tools available for measuring genetic diversity are briefly discussed and their source links (mostly) were provided to get easy access; thus, it improves the understanding of tools and its practical applicability to the researchers. PMID:25874132

  20. How Are Genetic Conditions Diagnosed?

    MedlinePLUS

    ... to birth, can provide clues to a genetic diagnosis. A personal medical history includes past health issues, hospitalizations and surgeries, ... about genetic testing and the importance of family medical history . ... about the diagnosis of specific genetic disorders are available in each ...

  1. Anthrax: Diagnosis

    MedlinePLUS

    ... EID Journal Articles Anthrax-Related MMWRs Medscape Commentaries Diagnosis Language: English Español (Spanish) Recommend on Facebook Tweet ... anthrax. The only ways to confirm an Anthrax diagnosis are: To measure antibodies or toxin in blood ...

  2. Dermatomyositis: Diagnosis

    MedlinePLUS

    ... Partners in Progress 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 ...

  3. Polymyositis: Diagnosis

    MedlinePLUS

    ... Partners in Progress 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 ...

  4. Genetics Home Reference: Cyclic neutropenia

    MedlinePLUS

    ... Recent literature OMIM Genetic disorder catalog Conditions > Cyclic neutropenia On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed January 2012 What is cyclic neutropenia? Cyclic neutropenia is a disorder that causes frequent ...

  5. Genetics Home Reference: Fryns syndrome

    MedlinePLUS

    ... ClinicalTrials.gov Research studies PubMed Recent literature OMIM Genetic disorder catalog Conditions > Fryns syndrome On this page: Description Genetic changes Inheritance Diagnosis Additional information Other names Glossary definitions Reviewed May ...

  6. Genetics Home Reference: Pfeiffer syndrome

    MedlinePLUS

    ... syndrome On this page: Description Genetic changes Inheritance Diagnosis Additional information Other names Glossary definitions Reviewed February 2008 What is Pfeiffer syndrome? Pfeiffer syndrome is a genetic disorder characterized by the premature fusion of certain skull ...

  7. Genetics Home Reference: Congenital hypothyroidism

    MedlinePLUS

    ... Recent literature OMIM Genetic disorder catalog Conditions > Congenital hypothyroidism On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed September 2015 What is congenital hypothyroidism? Congenital hypothyroidism is a partial or complete loss ...

  8. Genetics Home Reference: Retroperitoneal fibrosis

    MedlinePLUS

    ... Recent literature OMIM Genetic disorder catalog Conditions > Retroperitoneal fibrosis On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed July 2013 What is retroperitoneal fibrosis? Retroperitoneal fibrosis is a disorder in which inflammation ...

  9. Genetics Home Reference: Blau syndrome

    MedlinePLUS

    ... inherited version of the disorder called early-onset sarcoidosis. Where can I find information about diagnosis or ... Genetic Testing Registry: Blau syndrome Genetic Testing Registry: Sarcoidosis, early-onset Merck Manual Consumer Version: Overview of ...

  10. Genetics Home Reference: Beta thalassemia

    MedlinePLUS

    ... Recent literature OMIM Genetic disorder catalog Conditions > Beta thalassemia On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed September 2015 What is beta thalassemia? Beta thalassemia is a blood disorder that reduces ...

  11. Genetics Home Reference: VACTERL association

    MedlinePLUS

    ... Recent literature OMIM Genetic disorder catalog Conditions > VACTERL association On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed December 2011 What is VACTERL association? VACTERL association is a disorder that affects many ...

  12. Genetics Home Reference: Breast cancer

    MedlinePLUS

    ... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Breast cancer On this page: Description Genetic changes Inheritance Diagnosis ... names Glossary definitions Reviewed May 2015 What is breast cancer? Breast cancer is a disease in which certain ...

  13. 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

    Lee, Youjin

    2010-01-01

    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 ...

  14. Genetics Home Reference: Globozoospermia

    MedlinePLUS

    ... Genetic Testing Registry: Globozoospermia Health Topic: Assisted Reproductive Technology MedlinePlus Encyclopedia: Semen Analysis You might also find information on the diagnosis or management of globozoospermia in Educational resources and Patient support . ...

  15. [Genetic structure of the Iranian-speaking population of Azerbaijan from data on frequencies of immunologic and biochemical gene markers].

    PubMed

    Asadova, P Sh; Shne?der, Iu V; Shil'nikova, I N; Zhukova, O V

    2003-11-01

    The data on the genetic studies of Iranian-speaking populations from Azerbaijan (Talyshs and Tats) are presented. In these populations gene frequency distributions for the immunological (AB0, MN, Rhesus-D, -C, -E, P, Lewis, and Kell-Chellano) and biochemical (HP, GC, C'3, TF, 6PGD, GLO1, ESD, ACP1, and PGM1) gene markers were determined. Comparison of the genetic structure of the populations examined with the other Iranian-speaking populations (Persians and Kurds from Iran, Ossetins and Tajiks) and Azerbaijanis showed that Iranian-speaking populations from Azerbaijan were more close to Azerbaijanis, than to Iranian-speaking populations inhabiting other world regions. PMID:14714471

  16. From diagnosis to social diagnosis.

    PubMed

    Brown, Phil; Lyson, Mercedes; Jenkins, Tania

    2011-09-01

    In the past two decades, research on the sociology of diagnosis has attained considerable influence within medical sociology. Analyzing the process and factors that contribute to making a diagnosis amidst uncertainty and contestation, as well as the diagnostic encounter itself, are topics rich for sociological investigation. This paper provides a reformulation of the sociology of diagnosis by proposing the concept of 'social diagnosis' which helps us recognize the interplay between larger social structures and individual or community illness manifestations. By outlining a conceptual frame, exploring how social scientists, medical professionals and laypeople contribute to social diagnosis, and providing a case study of how the North American Mohawk Akwesasne reservation dealt with rising obesity prevalence to further illustrate the social diagnosis idea, we embark on developing a cohesive and updated framework for a sociology of diagnosis. This approach is useful not just for sociological research, but has direct implications for the fields of medicine and public health. Approaching diagnosis from this integrated perspective potentially provides a broader context for practitioners and researchers to understand extra-medical factors, which in turn has consequences for patient care and health outcomes. PMID:21705128

  17. Genetic diversity of allozymes in turnip (Brassica rapa L. var. rapa) from the Nordic area.

    PubMed

    Persson, K; Fält, A S; von Bothmer, R

    2001-01-01

    Genetic diversity and relationships based on isozymes were studied in 31 accessions of turnip (Brassica rapa L. var. rapa). The material included varieties, elite stocks, landraces and older turnip of slash-and-burn type from the Nordic area. A total of 9 isozyme loci and 26 alleles were studied. The isozyme systems were ACO, DIA, GPI, GOT, PGM, PGD and SKD. The level of heterozygosity was reduced in the landraces, but it was high for the variety group 'Ostersundom'. Turnip has a higher genetic variation than other crops within B. rapa and than in other species with the same breeding system. The genetic diversity showed that 18.7% of the genetic variation was within the accessions, and the total H tau value was 0.358. Gpi-I and Pgd-I showed the lowest variation compared with the other loci. The cluster analysis revealed five clusters, with one main cluster including 25 of the 31 accessions. The dendrogram indicated that the variety group 'Ostersundom' clustered together whereas the variety group 'Bortfelder' was associated with country of origin. The landraces were spread in different clusters. The 'slash-and-burn' type of turnip belonged to two groups. PMID:11525064

  18. Genetic diagnosis of X-linked dominant hypophosphatemic rickets in a cohort study: Tubular reabsorption of phosphate and 1,25(OH)2D serum levels are associated with PHEX mutation type

    PubMed Central

    2011-01-01

    Background Genetic Hypophosphatemic Rickets (HR) is a group of diseases characterized by renal phosphate wasting with inappropriately low or normal 1,25-dihydroxyvitamin D3 (1,25(OH)2D) serum levels. The most common form of HR is X-linked dominant HR (XLHR) which is caused by inactivating mutations in the PHEX gene. The purpose of this study was to perform genetic diagnosis in a cohort of patients with clinical diagnosis of HR, to perform genotype-phenotype correlations of those patients and to compare our data with other HR cohort studies. Methods Forty three affected individuals from 36 non related families were analyzed. For the genetic analysis, the PHEX gene was sequenced in all of the patients and in 13 cases the study was complemented by mRNA sequencing and Multiple Ligation Probe Assay. For the genotype-phenotype correlation study, the clinical and biochemical phenotype of the patients was compared with the type of mutation, which was grouped into clearly deleterious or likely causative, using the Mann-Whitney and Fisher's exact test. Results Mutations in the PHEX gene were identified in all the patients thus confirming an XLHR. Thirty four different mutations were found distributed throughout the gene with higher density at the 3' end. The majority of the mutations were novel (69.4%), most of them resulted in a truncated PHEX protein (83.3%) and were family specific (88.9%). Tubular reabsorption of phosphate (TRP) and 1,25(OH)2D serum levels were significantly lower in patients carrying clearly deleterious mutations than in patients carrying likely causative ones (61.39 ± 19.76 vs. 80.14 ± 8.80%, p = 0.028 and 40.93 ± 30.73 vs. 78.46 ± 36.27 pg/ml, p = 0.013). Conclusions PHEX gene mutations were found in all the HR cases analyzed, which was in contrast with other cohort studies. Patients with clearly deleterious PHEX mutations had lower TRP and 1,25(OH)2D levels suggesting that the PHEX type of mutation might predict the XLHR phenotype severity. PMID:21902834

  19. Carrier Diagnosis

    MedlinePLUS

    ... information to women who may indeed be carriers. Genetic tests such as mutation analysis look directly for the altered gene that’s responsible for hemophilia. This is the only way to be absolutely sure that a woman is ... other family members. However, genetic tests can be costly and may not be ...

  20. Genetic Screening

    PubMed Central

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

    2011-01-01

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

  1. Clinical Genetic Testing in Epilepsy

    PubMed Central

    2015-01-01

    New technologies for mutation detection in the human genome have greatly increased our understanding of epilepsy genetics. Application of genomic technologies in the clinical setting allows for more efficient genetic diagnosis in some patients; therefore, it is important to understand the types of tests available and the types of mutations that can be detected. Making a genetic diagnosis improves overall patient care by enhancing prognosis and recurrence risk counseling and informing treatment decisions. PMID:26316867

  2. Human prenatal diagnosis

    SciTech Connect

    Filkins, K.; Russo, J.F.

    1985-01-01

    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.

  3. Genetics Home Reference: X-linked adrenoleukodystrophy

    MedlinePLUS

    ... Program X-linked Adrenoleukodystrophy Database: Diagnosis of X-ALD You might also find information on the diagnosis ... Addison Complex Schilder disease Siemerling-Creutzfeldt disease X-ALD For more information about naming genetic conditions, see ...

  4. Population Genetics and Structure of Buryats from the Lake Baikal Region of Siberia

    E-print Network

    Novoradovsky, A. G.; Spitsyn, Victor A.; Druggirala, R.; Crawford, Michael H.

    1993-10-01

    and Structure of Buryats from the Lake Baikal Region of Siberia A.G. NOVORADOVSKY,1'3 V.A. SPITSYN,1 R. DUGGIRALA,2 AND M.H. CRAWFORD2 Abstract Genetic polymorphisms of blood groups, serum pro- teins, 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 rela- tively high frequencies of alleles ABO*B, RH*D , cerumen D, GC*1F , ACP1*B , ESD*2, and PGD*C. Significant...

  5. Fault diagnosis

    NASA Technical Reports Server (NTRS)

    Abbott, Kathy

    1990-01-01

    The objective of the research in this area of fault management is to develop and implement a decision aiding concept for diagnosing faults, especially faults which are difficult for pilots to identify, and to develop methods for presenting the diagnosis information to the flight crew in a timely and comprehensible manner. The requirements for the diagnosis concept were identified by interviewing pilots, analyzing actual incident and accident cases, and examining psychology literature on how humans perform diagnosis. The diagnosis decision aiding concept developed based on those requirements takes abnormal sensor readings as input, as identified by a fault monitor. Based on these abnormal sensor readings, the diagnosis concept identifies the cause or source of the fault and all components affected by the fault. This concept was implemented for diagnosis of aircraft propulsion and hydraulic subsystems in a computer program called Draphys (Diagnostic Reasoning About Physical Systems). Draphys is unique in two important ways. First, it uses models of both functional and physical relationships in the subsystems. Using both models enables the diagnostic reasoning to identify the fault propagation as the faulted system continues to operate, and to diagnose physical damage. Draphys also reasons about behavior of the faulted system over time, to eliminate possibilities as more information becomes available, and to update the system status as more components are affected by the fault. The crew interface research is examining display issues associated with presenting diagnosis information to the flight crew. One study examined issues for presenting system status information. One lesson learned from that study was that pilots found fault situations to be more complex if they involved multiple subsystems. Another was pilots could identify the faulted systems more quickly if the system status was presented in pictorial or text format. Another study is currently under way to examine pilot mental models of the aircraft subsystems and their use in diagnosis tasks. Future research plans include piloted simulation evaluation of the diagnosis decision aiding concepts and crew interface issues. Information is given in viewgraph form.

  6. Genetics Home Reference: Leber hereditary optic neuropathy

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Leber hereditary optic neuropathy On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed December 2013 What is Leber hereditary optic neuropathy? Leber hereditary optic neuropathy (LHON) is an inherited ...

  7. Genetics Home Reference: Giant axonal neuropathy

    MedlinePLUS

    ... 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 ...

  8. Genetics Home Reference: Small fiber neuropathy

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > Small fiber neuropathy On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed November 2012 What is small fiber neuropathy? Small fiber neuropathy is a condition characterized by ...

  9. Genetics Home Reference: Tuberous sclerosis complex

    MedlinePLUS

    ... complex On this page: Description Genetic changes Inheritance Diagnosis Additional information Other names Glossary definitions Reviewed December 2013 What is tuberous sclerosis complex? Tuberous sclerosis complex is a genetic disorder characterized by the growth of numerous noncancerous (benign) ...

  10. Genetics Home Reference: Intrahepatic cholestasis of pregnancy

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Intrahepatic cholestasis of pregnancy On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed May 2015 What is intrahepatic cholestasis of pregnancy? Intrahepatic cholestasis of pregnancy is a liver disorder ...

  11. Genetics Home Reference: Idiopathic pulmonary fibrosis

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > Idiopathic pulmonary fibrosis On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed April 2015 What is idiopathic pulmonary fibrosis? Idiopathic pulmonary fibrosis is a chronic, progressive lung ...

  12. Genetics Home Reference: Type 1 diabetes

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > Type 1 diabetes On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed March 2013 What is type 1 diabetes? Type 1 diabetes is a disorder characterized by ...

  13. Genetics Home Reference: Pulmonary arterial hypertension

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > Pulmonary arterial hypertension On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed September 2012 What is pulmonary arterial hypertension? Pulmonary arterial hypertension is a progressive disorder characterized ...

  14. Genetics Home Reference: Keratoderma with woolly hair

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Keratoderma with woolly hair On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed November 2015 What is keratoderma with woolly hair? Keratoderma with woolly hair is a group of ...

  15. Genetics Home Reference: Juvenile myoclonic epilepsy

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > Juvenile myoclonic epilepsy On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed September 2015 What is juvenile myoclonic epilepsy? Juvenile myoclonic epilepsy is a condition characterized by ...

  16. Genetics Home Reference: Pyridoxine-dependent epilepsy

    MedlinePLUS

    ... 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 ...

  17. Genetics Home Reference: Lafora progressive myoclonus epilepsy

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Lafora progressive myoclonus epilepsy On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed July 2009 What is Lafora progressive myoclonus epilepsy? Lafora progressive myoclonus epilepsy is a brain disorder ...

  18. The importance of analysis of long-range rearrangement of BRCA1 and BRCA2 in genetic diagnosis of familial breast cancer.

    PubMed

    Kwong, Ava; Chen, Jiawei; Shin, Vivian Y; Ho, John C W; Law, Fian B F; Au, Chun Hang; Chan, Tsun-Leung; Ma, Edmond S K; Ford, James M

    2015-09-01

    Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers. Identification of BRCA mutations greatly improves the preventive strategies and management of breast cancer. Sanger sequencing has been the gold standard in identifying these mutations. However, 4-28% of inherited BRCA mutations may be due to large genomic rearrangements (LGRs), which could be missed by using Sanger sequencing alone. Our aim is to evaluate the pick-up rate of LGRs in our cohort. A total of 1,236 clinically high-risk patients with breast and/or ovarian cancers were recruited through The Hong Kong Hereditary Breast Cancer Family Registry from 2007 to 2014. Full gene sequencing (either Sanger or next generation sequencing) and multiplex ligation-dependent probe amplification (MLPA) were performed. We identified 120 deleterious BRCA mutations: 57 (4.61%) were in BRCA1 and 63 (5.10%) were in BRCA2. LGRs accounted for 6.67% (8 of 120) of all BRCA mutations, whereas 8.77 % (5 of 57) were BRCA1 mutations and 4.76% (3 of 63) were BRCA2 mutations. Through this integrated approach, both small nucleotide variations and LGRs could be detected. We suggest that MLPA should be incorporated into the standard practice for genetic testing to avoid false-negative results, which would greatly affect the management of these high-risk families. PMID:26271414

  19. A handheld flow genetic analysis system (FGAS): towards rapid, sensitive, quantitative and multiplex molecular diagnosis at the point-of-care level.

    PubMed

    Shu, Bowen; Zhang, Chunsun; Xing, Da

    2015-06-21

    A handheld flow genetic analysis system (FGAS) is proposed for rapid, sensitive, multiplex and real-time quantification of nucleic acids at the point-of-care (POC) level. The FGAS includes a helical thermal-gradient microreactor and a microflow actuator, as well as control circuitry for temperature, fluid and power management, and smartphone fluorescence imaging. All of these features are integrated into a field-portable and easy-to-use molecular diagnostic platform powered by lithium batteries. Due to the unique design of the microreactor, not only steady temperatures for denaturation and annealing/extension but also a linear thermal gradient for spatial high-resolution melting can be achieved through simply maintaining a single heater at constant temperature. The smartphone fluorescence imaging system has a wide field of view that captures all PCR channels of the microreactor in a single snapshot without the need for any mechanical scanning. By these designs, the FGAS enables real-time monitoring of the temporal and spatial fluorescence signatures of amplicons during continuous-flow amplification. On the current FGAS, visual detection of as little as 10 copies per ?L of genomic DNA of Salmonella enterica was achieved in 15 min, with real-time quantitative detection of the DNA over 6 orders of magnitude concentration from 10(6) to 10(1) copies per ?L also completed in 7.5-15 min. In addition, multiple pathogenic DNA targets could be simultaneously discriminated with direct bar-chart readout or multiplex spatial melting in serial flow. We anticipate that the FGAS has great potential to become a next-generation gene analyzer for POC molecular diagnostics. PMID:25953325

  20. Genetics and epilepsy

    PubMed Central

    Steinlein, Ortrud K.

    2008-01-01

    The term “epilepsy” describes a heterogeneous group of disorders, most of them caused by interactions between several or even many genes and environmental factors. Much rarer are the genetic epilepsies that are due to single-gene mutations or defined structural chromosomal aberrations, such as microdeletions. The discovery of several of the genes underlying these rare genetic epilepsies has already considerably contributed to our understanding of the basic mechanisms epileptogenesis. The progress made in the last 15 years in the genetics of epilepsy is providing new possibilities for diagnosis and therapy. Here, different genetic epilepsies are reviewed as examples, to demonstrate the various pathways that can lead from genes to seizures. PMID:18472482

  1. Melanoma Diagnosis

    NASA Astrophysics Data System (ADS)

    Horsch, Alexander

    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.

  2. Genetic Mapping

    MedlinePLUS

    ... Fact Sheets Genetic Mapping En Español: Mapeo Genético Genetic Mapping What is genetic mapping? How do researchers ... genetic map? What are genetic markers? What is genetic mapping? Among the main goals of the Human ...

  3. Genetics Home Reference: Canavan disease

    MedlinePLUS

    ... Genetic Testing Registry: Spongy degeneration of central nervous system MedlinePlus Encyclopedia: Canavan Disease You might also find information on the diagnosis or management of Canavan disease in Educational resources and Patient support . General information about the ...

  4. Genetics Home Reference: Familial cylindromatosis

    MedlinePLUS

    ... Center Information about genetic conditions and rare diseases Educational resources Information pages Patient support For patients and ... the diagnosis or management of familial cylindromatosis in Educational resources and Patient support . General information about the ...

  5. Molecular diagnosis: Implications for ophthalmology.

    PubMed

    Rosenbaum, James T; Sibley, Cailin H; Choi, Dongseok; Harrington, Christina A; Planck, Stephen R

    2016-01-01

    The effort to subdivide diseases and to individualize therapies based on characteristics of the patient has been labeled precision medicine. Jameson and Longo define precision medicine as "treatments targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic or psychosocial characteristics that distinguish a given patient from other patients with similar clinical presentations" (Jameson and Longo, 2015). We illustrate how molecular diagnosis can be applied to orbital inflammatory disease to achieve the goals of precision medicine. PMID:26608807

  6. Prenatal Diagnosis of WAGR Syndrome

    PubMed Central

    Tezcan, Berrin; Rich, Philip; Bhide, Amarnath

    2015-01-01

    Wilm's tumour, aniridia, genitourinary abnormalities, and mental retardation (WAGR) syndrome is a rare genetic disorder with an estimated prevalence of 1 in 500,000 to 1 million. It is a contiguous gene syndrome due to deletion at chromosome 11p13 in a region containing WT1 and PAX6 genes. Children with WAGR syndrome mostly present in the newborn/infancy period with sporadic aniridia. The genotypic defects in WAGR syndrome have been well established. However, antenatal ultrasonographic presentation of this syndrome has never been reported. Prenatal diagnosis of this condition is possible in some cases with careful ultrasound examination of classical and nonclassical manifestations of this syndrome. The key point for this rare diagnosis was the decision to perform chromosomal microarray analysis after antenatal diagnosis of absent corpus callosum and absent cavum septum pellucidum, as this finding mandates search for potentially associated genetic disorders. We report a case of WAGR syndrome diagnosed prenatally at 29-week gestation. The diagnosis of the anomaly was based on two- and three-dimensional ultrasound as well as fetal MRI scan and microarray analysis. The ultrasonographic findings included borderline ventriculomegaly, absent corpus callosum, and absent cavum septum pellucidum. Cytogenetic results from the amniotic fluid confirmed WAGR syndrome. Parental karyotype was normal, with no evidence of copy number change, deletion, or rearrangement of this region of chromosome 11. PMID:26605098

  7. Obtaining genetic testing in pediatric epilepsy.

    PubMed

    Ream, Margie A; Patel, Anup D

    2015-10-01

    The steps from patient evaluation to genetic diagnosis remain complicated. We discuss some of the genetic testing methods available along with their general advantages and disadvantages. We briefly review common pediatric epilepsy syndromes with strong genetic association and provide a potentially useful algorithm for genetic testing in drug-resistant epilepsy. We performed an extensive literature review of available information as it pertains to genetic testing and genetics in pediatric epilepsy. If a genetic disorder is suspected as the cause of epilepsy, based on drug resistance, family history, or clinical phenotype, timely diagnosis may reduce overall cost, limit the diagnostic odyssey that can bring much anxiety to families, improve prognostic accuracy, and lead to targeted therapy. Interpretation of complicated results should be performed only in collaboration with geneticists and genetic counselors, unless the ordering neurologist has a strong background in and understanding of genetics. Genetic testing can play an important role in the care provided to patients with epilepsy. PMID:26345167

  8. [Clinical diagnosis].

    PubMed

    Furukawa, Katsutoshi; Kamada, Maki; Ishiki, Aiko; Tomita, Naoki; Arai, Hiroyuki

    2014-04-01

    The commonly followed definition of dementia is the one described by the International Statistical Classification of Diseases, 10th Revision (ICD-10, World Health Organization) or the Diagnostic and Statistical Manual of Mental Disorders (DSM-V, American Psychiatric Association). The most important aspect in the diagnosis of dementia is the assessment of overall mental and functions, including living environment, activities of daily living, cognition, mental status, and behavior. Physicians should diagnose dementia on the basis of not only cognitive test results or radiological findings but also other available information, including that obtained from the families or caregivers. Tests for the quantitative evaluation of cognitive function and dementia include the Mini-Mental State Examination (MMSE), Hasegawa Dementia Scale Revised (HDS-R), Clinical Dementia Rating (CDR), and Wechsler Memory Scale-Revised (WMS-R). PMID:24796095

  9. Copyright 2004 by the Genetics Society of America DOI: 10.1534/genetics.104.027649

    E-print Network

    Matzkin, Luciano M.

    and pattern of reports for six other genes (Adh, Gpdh, Pgm, G6pd, 6Pgd, Hex-C), presents a picture mutations. DROSOPHILA melanogaster is an Afrotropical spe- hemispheres at the Adh, Gpdh, G6pd, and 6Pgd loci

  10. [Etiology and diagnosis of intellectual disability].

    PubMed

    Yang, Pu; Gui, Bao-Heng; Wu, Ling-Qian

    2015-06-01

    Intellectual disability, occurring in 1%-3% of the general population, is a common disease of the nervous system in children. Since diverse genetic and environmental factors contribute to its pathogenesis, the etiological diagnosis of intellectual disability is challenging with respect to the selection of diagnostic tests. It is important to determine the etiology of intellectual disability for the assessment of prognosis, treatment and the family plan. This paper summarizes the research progress in etiology and diagnosis for intellectual disability and introduces the recommended clinical genetics diagnostic approach from the American Academy of Pediatrics. PMID:26108310

  11. Genetics Home Reference: Hepatic veno-occlusive disease with immunodeficiency

    MedlinePLUS

    ... might also find information on the diagnosis or management of VODI in Educational resources and Patient support . General information about the diagnosis and management of genetic conditions is available in the Handbook. ...

  12. Challenges in the diagnosis of Marfan syndrome.

    PubMed

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

    2006-06-19

    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

  13. Diagnosis of automotive fuel cell power generators

    NASA Astrophysics Data System (ADS)

    Hissel, D.; Péra, M. C.; Kauffmann, J. M.

    Most of car manufacturers around the world have launched important research programs on the integration of fuel cell (FC) power generators into cars. Despite the first achievements, fuel cell systems are still badly known, particularly when talking about fault diagnosis and predictive maintenance. This paper proposes a first step in this way by introducing a simple but also efficient diagnosis-oriented model of a proton exchange membrane fuel cell (PEMFC). The considered diagnosis model is here a fuzzy one and is tuned thanks to genetic algorithms.

  14. The value of cardiac genetic testing.

    PubMed

    Ingles, Jodie; Semsarian, Christopher

    2014-08-01

    Genetic testing is an important and necessary aspect of the management of families with cardiac genetic conditions. Commercial genetic tests are available for most cardiac genetic diseases, and increasing uptake amongst patients has contributed to a vastly improved knowledge of the genetic basis of these diseases. The incredible advances in genetic technologies have translated to faster, more comprehensive, and inexpensive commercial genetic tests and has completely changed the landscape of commercial genetic testing in recent years. While there are enormous challenges, mostly relating to interpretation of variants, the value of a genetic diagnosis should not be underestimated. In almost all cases, the single greatest utility is for the predictive genetic testing of family members. This review will describe the value of cardiac genetic testing in the current climate of rapid genetic advancements. PMID:25066489

  15. Plague Diagnosis and Treatment

    MedlinePLUS

    ... Officials Veterinarians Prevention History of Plague Resources FAQ Diagnosis and Treatment Recommend on Facebook Tweet Share Compartir Detailed Diagnosis and Treatment Recommendations Diagnosis Doctors examining a bubo caused by plague. Plague ...

  16. Genetics Home Reference: Head and neck squamous cell carcinoma

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Head and neck squamous cell carcinoma On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed January 2015 What is head and neck squamous cell carcinoma? Squamous cell carcinoma is a cancer that arises ...

  17. Genetics Home Reference: Glycogen storage disease type V

    MedlinePLUS

    ... Genetic disorder catalog Conditions > Glycogen storage disease type V On this page: Description Genetic changes Inheritance Diagnosis ... June 2014 What is glycogen storage disease type V? Glycogen storage disease type V (also known as ...

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

    MedlinePLUS

    ... 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 ...

  19. [Genetic testing in the context of the revision of the French law on bioethics].

    PubMed

    Bonneau, D; Marlin, S; Sanlaville, D; Dupont, J-M; Sobol, H; Gonzales, M; Le Merrer, M; Malzac, P; Razavi, F; Manouvrier, S; Odent, S; Stoppa-Lyonnet, D

    2010-10-01

    This article focuses on six questions raised by genetic testing in human: (1) the use of genetic tests, (2) information given to relatives of patients affected with genetic disorders, (3) prenatal and preimplantatory diagnosis for late onset genetic diseases and the use of pangenomic tests in prenatal diagnosis, (4) direct-to-consumer genetic testing, (5) population screening in the age of genomic medicine and (6) incidental findings when genetic testing are used. PMID:20116936

  20. Genetic counseling services and development of training programs in Malaysia.

    PubMed

    Lee, Juliana Mei-Har; Thong, Meow-Keong

    2013-12-01

    Genetic counseling service is urgently required in developing countries. In Malaysia, the first medical genetic service was introduced in 1994 at one of the main teaching hospitals in Kuala Lumpur. Two decades later, the medical genetic services have improved with the availability of genetic counseling, genetic testing and diagnosis, for both paediatric conditions and adult-onset inherited conditions, at four main centers of medical genetic services in Malaysia. Prenatal diagnosis services and assisted reproductive technologies are available at tertiary centres and private medical facilities. Positive developments include governmental recognition of Clinical Genetics as a subspecialty, increased funding for genetics services, development of medical ethics guidelines, and establishment of support groups. However, the country lacked qualified genetic counselors. Proposals were presented to policy-makers to develop genetic counseling courses. Challenges encountered included limited resources and public awareness, ethical dilemmas such as religious and social issues and inadequate genetic health professionals especially genetic counselors. PMID:23615969

  1. New Genetics

    MedlinePLUS

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

  2. Genetic Counseling

    MedlinePLUS

    Genetic counseling provides information and support to people who have, or may be at risk for, genetic disorders. ... genetic testing. There are many reasons to seek genetic counseling. You may consider it if you Have a ...

  3. Medical genetics

    SciTech Connect

    Nora, J.J.; Fraser, F.C.

    1989-01-01

    This book presents a discussion of medical genetics for the practitioner treating or counseling patients with genetic disease. It includes a discussion of the relationship of heredity and diseases, the chromosomal basis for heredity, gene frequencies, and genetics of development and maldevelopment. The authors also focus on teratology, somatic cell genetics, genetics and cancer, genetics of behavior.

  4. Molecular Diagnosis of Cystic Fibrosis.

    PubMed

    Deignan, Joshua L; Grody, Wayne W

    2016-01-01

    This unit describes a recommended approach to identifying causal genetic variants in an individual suspected of having cystic fibrosis. An introduction to the genetics and clinical presentation of cystic fibrosis is initially presented, followed by a description of the two main strategies used in the molecular diagnosis of cystic fibrosis: (1) an initial targeted variant panel used to detect only the most common cystic fibrosis-causing variants in the CFTR gene, and (2) sequencing of the entire coding region of the CFTR gene to detect additional rare causal CFTR variants. Finally, the unit concludes with a discussion regarding the analytic and clinical validity of these approaches. © 2016 by John Wiley & Sons, Inc. PMID:26724724

  5. Genetics for the ophthalmologist

    PubMed Central

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

    2012-01-01

    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

  6. Genetics Home Reference: Congenital hepatic fibrosis

    MedlinePLUS

    ... Research studies PubMed Recent literature Conditions > Congenital hepatic fibrosis On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed January 2012 What is congenital hepatic fibrosis? Congenital hepatic fibrosis is a disease of the ...

  7. Genetics Home Reference: Multiple familial trichoepithelioma

    MedlinePLUS

    ... Center Information about genetic conditions and rare diseases Educational resources Information pages Patient support For patients and ... diagnosis or management of multiple familial trichoepithelioma in Educational resources and Patient support . General information about the ...

  8. The Genetics of Colorectal Cancer.

    PubMed

    Jasperson, Kory; Burt, Randall W

    2015-10-01

    The hereditary colorectal cancer syndromes comprise a heterogeneous group of conditions with varying cancer risks, gastrointestinal polyp types, nonmalignant findings, and inheritance patterns. Although each one is unique in its own right, these syndromes often have overlapping features, making diagnoses difficult in select cases. Obtaining accurate polyp history (histologic type, number, location, and age of onset), cancer history (location, type, and age of onset), and other nonmalignant features is imperative in determining the likely disease diagnosis and thereby the appropriate genetic tests for precise diagnosis in a timely fashion. This process often necessitates collaboration among surgical oncology team members and genetic counselors. PMID:26363537

  9. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia

    Cancer.gov

    There is incomplete understanding of genetic heterogeneity and clonal evolution during cancer progression. Here we use deep whole-exome sequencing to describe the clonal architecture and evolution of 20 pediatric B-acute lymphoblastic leukaemias from diagnosis to relapse. We show that clonal diversity is comparable at diagnosis and relapse and clonal survival from diagnosis to relapse is not associated with mutation burden.

  10. Genetic algorithms

    NASA Technical Reports Server (NTRS)

    Wang, Lui; Bayer, Steven E.

    1991-01-01

    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.

  11. Tetanus: Diagnosis and Treatment

    MedlinePLUS

    ... Links Tetanus Vaccination Maternal and Neonatal Tetanus Elimination Diagnosis and Treatment Recommend on Facebook Tweet Share Compartir ... should be given along with treatment. Related Page Diagnosis/Treatment for Clinicians Related Links Tetanus Vaccination Maternal ...

  12. Symptoms and Diagnosis

    MedlinePLUS

    ... Frequently Asked Questions Glossary Downloadable Publications Symptoms and Diagnosis If you are new to dystonia, it can ... conditions. The words used to describe your specific diagnosis may be confusing. To accurately describe the form ...

  13. Diagnosis of Ataxia

    MedlinePLUS

    ... 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 ...

  14. Diagnosis of Leishmaniasis

    MedlinePLUS

    ... CDC.gov . Parasites - Leishmaniasis Parasites Home Share Compartir Diagnosis Light-microscopic examination of a stained bone marrow ... are done. More on: Resources for Health Professionals: Diagnosis Print page Get email updates Subscribe to RSS ...

  15. Porphyrins and Porphyria Diagnosis

    MedlinePLUS

    ... are here Home Testing for Porphyria Porphyrins & Porphyria diagnosis The porphyrias are caused by deficiencies of enzymes ... that accumulate are very large. This enables a diagnosis of active Porphyria to be made quite readily. ** ...

  16. Diphtheria Diagnosis and Treatment

    MedlinePLUS

    ... Action Coalition (IAC) Diphtheria and the Alaskan Iditarod Diagnosis and Treatment Recommend on Facebook Tweet Share Compartir Getting treatment for diphtheria quickly is important. Diagnosis of diphtheria is usually made based on signs ...

  17. Birth Defects Diagnosis

    MedlinePLUS

    ... Websites About Us Information For... Media Policy Makers Diagnosis Language: English Español (Spanish) Recommend on Facebook Tweet ... A screening test does not provide a specific diagnosis—that requires a diagnostic test (see below). A ...

  18. Body Lice Diagnosis

    MedlinePLUS

    ... Treatment FAQs Malathion FAQs Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ... Frequently Asked Questions (FAQs) Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ...

  19. Head Lice: Diagnosis

    MedlinePLUS

    ... Treatment FAQs Malathion FAQs Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ... Frequently Asked Questions (FAQs) Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ...

  20. Pubic "Crab" Lice Diagnosis

    MedlinePLUS

    ... Treatment FAQs Malathion FAQs Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ... Frequently Asked Questions (FAQs) Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ...

  1. Coping with a Diagnosis

    MedlinePLUS

    ... Email Home Share Page Print Page Email Page Home / Understanding Parkinson's Coping with a Diagnosis Diagnosis Parkinson's Disease: You Are Not Alone Video Secrets, Myths and Misconceptions What is Parkinson’s ...

  2. Food Allergy Diagnosis

    MedlinePLUS

    ... Skip Content Marketing Share this: Main Content Area Food Allergy Diagnosis © iStockphoto On this page Detailed History ... diagnosis of food allergy. back to top Oral food challenge Caution Because oral food challenges can cause ...

  3. Genetics Home Reference: Multiple system atrophy

    MedlinePLUS

    ... information on the diagnosis or management of multiple system atrophy in Educational resources and Patient support . General information about the diagnosis and management of genetic conditions is available in the Handbook. ... about multiple system atrophy? You may find the following resources about ...

  4. Genetic Counseling

    MedlinePLUS

    ... Articles Genetic Counseling Information For... Media Policy Makers Genetic Counseling Language: English Español (Spanish) Recommend on Facebook ... informed decisions about testing and treatment. Reasons for Genetic Counseling There are many reasons that people go ...

  5. Genetic technologies and ethics.

    PubMed

    Ardekani, Ali M

    2009-01-01

    In the past decade, the human genome has been completely sequenced and the knowledge from it has begun to influence the fields of biological and social sciences in fundamental ways. Identification of about 25000 genes in the human genome is expected to create great benefits in diagnosis and treatment of diseases in the coming years. However, Genetic technologies have also created many interesting and difficult ethical issues which can affect the human societies now and in the future. Application of genetic technologies in the areas of stem cells, cloning, gene therapy, genetic manipulation, gene selection, sex selection and preimplantation diagnosis has created a great potential for the human race to influence and change human life on earth as we know it today. Therefore, it is important for leaders of societies in the modern world to pay attention to the advances in genetic technologies and prepare themselves and those institutions under their command to face the challenges which these new technologies induce in the areas of ethics, law and social policies. PMID:23908725

  6. Mitochondrial disorders: Challenges in diagnosis & treatment

    PubMed Central

    Khan, Nahid Akhtar; Govindaraj, Periyasamy; Meena, Angamuthu Kannan; Thangaraj, Kumarasamy

    2015-01-01

    Mitochondrial dysfunctions are known to be responsible for a number of heterogenous clinical presentations with multi-systemic involvement. Impaired oxidative phosphorylation leading to a decrease in cellular energy (ATP) production is the most important cause underlying these disorders. Despite significant progress made in the field of mitochondrial medicine during the last two decades, the molecular mechanisms underlying these disorders are not fully understood. Since the identification of first mitochondrial DNA (mtDNA) mutation in 1988, there has been an exponential rise in the identification of mtDNA and nuclear DNA mutations that are responsible for mitochondrial dysfunction and disease. Genetic complexity together with ever widening clinical spectrum associated with mitochondrial dysfunction poses a major challenge in diagnosis and treatment. Effective therapy has remained elusive till date and is mostly efficient in relieving symptoms. In this review, we discuss the important clinical and genetic features of mitochondrials disorders with special emphasis on diagnosis and treatment. PMID:25857492

  7. Genetics of Canine Primary Glaucomas.

    PubMed

    Komáromy, András M; Petersen-Jones, Simon M

    2015-11-01

    Primary glaucomas are a leading cause of incurable vision loss in dogs. Based on their specific breed predilection, a genetic cause is suspected to be responsible, and affected dogs should be excluded from breeding. Despite the high prevalence of primary glaucomas in dogs, their genetics have been studied in only a small number of breeds. The identification of canine glaucoma disease genes, and the development of genetic tests, will help to avoid the breeding of affected dogs in the future and will allow for earlier diagnosis and potentially more effective therapy. PMID:26277300

  8. [LCAT deficiency: a nephrological diagnosis].

    PubMed

    Boscutti, Giuliano; Calabresi, Laura; Pizzolitto, Stefano; Boer, Emanuela; Bosco, Manuela; Mattei, Piero Luigi; Martone, Massimiliano; Milutinovic, Neva; Berbecar, Dorina; Beltram, Elisabetta; Franceschini, Guido

    2011-01-01

    A genetic mendelian autosomal recessive condition of deficiency of lecithin- cholesterol acyltransferase (LCAT) can produce two different diseases: one highly interesting nephrologic picture of complete enzymatic deficiency (lecithin:cholesterol acyltransferase deficiency; OMIM ID #245900; FLD), characterized by the association of dyslipidemia, corneal opacities, anemia and progressive nephropathy; and a partial form (fish eye disease; OMIM ID #136120; FED) with dyslipidemia and progressive corneal opacities only. The diagnosis of FLD falls first of all under the competence of nephrologists, because end-stage renal disease appears to be its most severe outcome. The diagnostic suspicion is based on clinical signs (corneal opacities, more severe anemia than expected for the degree of chronic renal failure, progressive proteinuric nephropathy) combined with histology obtained by kidney biopsy (glomerulopathy evolving toward sclerosis with distinctive lipid deposition). However, the final diagnosis, starting with a finding of extremely low levels of HDL-cholesterol, requires collaboration with lipidology Centers that can perform sophisticated investigations unavailable in common laboratories. To be heterozygous for a mutation of the LCAT gene is one of the monogenic conditions underlying primary hypoalphalipoproteinemia (OMIM ID #604091). This disease, which is characterized by levels of HDL-cholesterol below the 5th percentile of those of the examined population (<28 mg/dL for Italians), has heritability estimates between 40% and 60% and is considered to be a predisposing condition for coronary artery disease. Nevertheless, some monogenic forms, and especially those associated with LCAT deficiency, seem to break the rule, confirming once more the value of a proper diagnosis before drawing prognostic conclusions from a laboratory marker. As in many other rare illnesses, trying to discover all the existing cases will contribute to allow studies broad enough to pave the way for further therapies, in this case also fostering the production by industries of the lacking enzyme by genetic engineering. Epidemiological studies, although done on selected populations such as hypoalphalipoproteinemia patients on dialysis and with the effective genetic tools of today, have been disappointing in elucidating the disease. Spreading the clinical knowledge of the disease and its diagnostic course among nephrologists seems to be the best choice, and this is the aim of our work. PMID:21809306

  9. Congenital metabolic diseases: Diagnosis and treatment

    SciTech Connect

    Wapnir, R.A.

    1985-01-01

    This book contains eight parts, each consisting of several papers. The part titles are: The Heritage of Sir Archibald Garrod; New Approaches to the Diagnosis and Treatment of Genetic Disease; Achievements, New Trends, and Policies in the Detection of Inborn Errors of Metabolism; Disorders of Amino Acid Metabolism; Diseases of Energy Metabolism; Problems of Abnormal Storage Diseases; Inherited Diseases of Membrane Transport and Receptors; and Inborn Errors of Purine Metabolism and Urea Synthesis.

  10. Family Assessment and Genetic Counseling.

    ERIC Educational Resources Information Center

    Carpenter, Pat; And Others

    Presented are two papers from a panel discussion on prenatal diagnosis and genetic counseling with families. D. Blackston (director of the Developmental Evaluation Clinic, Decatur, Georgia) points out that a concise family history, pregnancy and birth data, developmental history, careful physical examination, and appropriate laboratory studies are…

  11. A genetic prion disease Background information:Background information

    E-print Network

    Brutlag, Doug

    on homo- or heterozygosity · Genetic counseling ­ Prenatal and pre-implantation diagnosis for familyA genetic prion disease #12;Background information:Background information: About PrionsAbout Prions· Structure ­ Misfolded proteins ­ Not alive; no genetic material · Pathogenesis ­ Convert normal proteins

  12. The Diagnosis of Sarcoidosis.

    PubMed

    Govender, Praveen; Berman, Jeffrey S

    2015-12-01

    Sarcoidosis is a diagnosis of exclusion; there exists neither a pathognomonic clinical feature nor a perfect diagnostic test. Missed diagnosis and overdiagnosis are common. A careful history and physical examination look for "footprints" of sarcoidosis or features suggesting alternative diagnoses. Some presentations are classic and do not require tissue confirmation. A tissue biopsy should be performed if doubt exists. Sampling intrathoracic disease by transbronchial or ultrasound-guided biopsy of mediastinal lymph nodes provide high diagnostic yield with low complication rates. Even with tissue confirmation, diagnosis is never secure and follow-up is required to be fully confident of the diagnosis. PMID:26593135

  13. Myths in the Diagnosis and Management of Orbital Tumors

    PubMed Central

    Gündüz, Kaan; Yan?k, Özge

    2015-01-01

    Orbital tumors constitute a group of diverse lesions with a low incidence in the population. Tumors affecting the eye and ocular adnexa may also secondarily invade the orbit. Lack of accumulation of a sufficient number of cases with a specific diagnosis at various orbital centers, the paucity of prospective randomized studies, animal model studies, tissue bank, and genetic studies led to the development of various myths regarding the diagnosis and treatment of orbital lesions in the past. These myths continue to influence the diagnosis and treatment of orbital lesions by orbital specialists. This manuscript discusses some of the more common myths through case summaries and a review of the literature. Detailed genotypic analysis and genetic classification will provide further insight into the pathogenesis of many orbital diseases in the future. This will enable targeted treatments even for diseases with the same histopathologic diagnosis. Phenotypic variability within the same disease will be addressed using targeted treatments.

  14. Case for diagnosis*

    PubMed Central

    Sano, Daniela Tiemi; de Melo, Luciana Valentini; Tebcherani, Antonio José; Sanchez, Ana Paula Galli

    2014-01-01

    Focal acral hyperkeratosis is a rare genodermatosis with an autosomal dominant pattern of inheritance. It is characterized by usually asymptomatic keratotic papules along the borders of the hands and/or feet. The main differential diagnosis is acrokeratoelastoidosis of Costa, which differs from the former only by not presenting elastorrhexis in histopathological examination, thus requiring this exam for a correct diagnosis. PMID:25184932

  15. New trend in non-invasive prenatal diagnosis.

    PubMed

    Ferrari, M; Carrera, P; Lampasona, V; Galbiati, S

    2015-12-01

    The presence of fetal DNA in maternal plasma represents a source of genetic material which can be obtained non-invasively. To date, the translation of noninvasive prenatal diagnosis from research into clinical practice has been rather fragmented, and despite the advances in improving the analytical sensitivity of methods, distinguishing between fetal and maternal sequences remains very challenging. Thus, the field of noninvasive prenatal diagnosis of genetic diseases has yet to attain a routine application in clinical diagnostics. On the contrary, fetal sex determination in pregnancies at high risk of sex-linked disorders, tests for fetal RHD genotyping and non-invasive assessment of chromosomal aneuploidies are now available worldwide. PMID:25542529

  16. Late diagnosis of Lesch-Nyhan disease variant

    PubMed Central

    Doucet, Brian Percy; Jegatheesan, Dev; Burke, John

    2013-01-01

    A 30-year-old man was referred for investigation and management of hyperuricaemia. History included recurrent nephrolithiasis and chronic gout with poor response to medical management. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) enzyme activity was investigated and found to be deficient confirming the diagnosis of Lesch-Nyhan disease. Hyperuricaemia was treated with allopurinol. To prevent nephrolithiasis, the patient was instructed to avoid dehydration and aim for a minimum urine output of 2?L/day. Urinary alkalinisation with potassium citrate was started. The patient was referred for genetic counselling. This case discusses the genetics, pathophysiology, clinical manifestations, diagnosis and management of HGPRT deficiency. PMID:24326440

  17. Clinical and microbiological diagnosis of oral candidiasis

    PubMed Central

    Jiménez-Soriano, Yolanda

    2013-01-01

    Introduction: Candidiasis or oral candidiasis is the most frequent mucocutaneous mycosis of the oral cavity. It is produced by the genus Candida, which is found in the oral cavity of 53% of the general population as a common commensal organism. One hundred and fifty species have been isolated in the oral cavity, and 80% of the isolates correspond to Candida albicans, which can colonize the oral cavity alone or in combination with other species. Transformation from commensal organism to pathogen depends on the intervention of different predisposing factors that modify the microenvironment of the oral cavity and favor the appearance of opportunistic infection. The present study offers a literature review on the diagnosis of oral candidiasis, with the purpose of establishing when complementary microbiological techniques for the diagnosis of oral candidiasis should be used, and which techniques are most commonly employed in routine clinical practice in order to establish a definitive diagnosis. Materials and methods: A Medline-PubMed, Scopus and Cochrane search was made covering the last 10 years. Results: The diagnosis of oral candidiasis is fundamentally clinical. Microbiological techniques are used when the clinical diagnosis needs to be confirmed, for establishing a differential diagnosis with other diseases, and in cases characterized by resistance to antifungal drugs. Biopsies in turn are indicated in patients with hyperplastic candidiasis. Staining (10% KOH) and culture (Sabouraud dextrose agar) are the methods most commonly used for diagnosing primary candidiasis. Identification of the individual species of Candida is usually carried out with CHROMagar Candida®. For the diagnosis of invasive candidiasis, and in cases requiring differentiation between C. albicans and C. dubliniensis, use is made of immunological and genetic techniques such as ELISA and PCR. Key words:Clinical, oral candidiasis, microbiology. PMID:24455095

  18. Genetic Disorders

    MedlinePLUS

    ... This can cause a medical condition called a genetic disorder. You can inherit a gene mutation from ... during your lifetime. There are three types of genetic disorders: Single-gene disorders, where a mutation affects ...

  19. Genetic Discrimination

    MedlinePLUS

    ... Informed Consent for Genomics Research Intellectual Property Online Bioethics Resources Privacy in Genomics Regulation of Genetic Tests ... Medicine: Policy Implications for Research and Medicine Online Bioethics Resources Privacy in Genomics Regulation of Genetic Tests · ...

  20. Genetic counseling

    MedlinePLUS

    ... certain diseases are also often determined by genes. Genetic counseling is the process where parents can learn more ... up to you whether or not to have genetic counseling and testing. You will want to think about ...

  1. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia | Office of Cancer Genomics

    Cancer.gov

    There is incomplete understanding of genetic heterogeneity and clonal evolution during cancer progression. Here we use deep whole-exome sequencing to describe the clonal architecture and evolution of 20 pediatric B-acute lymphoblastic leukaemias from diagnosis to relapse. We show that clonal diversity is comparable at diagnosis and relapse and clonal survival from diagnosis to relapse is not associated with mutation burden.

  2. Genetic modification and genetic determinism

    PubMed Central

    Resnik, David B; Vorhaus, Daniel B

    2006-01-01

    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

  3. Prenatal diagnosis in Belgium.

    PubMed

    Vamos, E; Vandenberghe, K; Cassiman, J J

    1997-01-01

    Prenatal diagnoses (PND) in Belgium are performed exclusively in licensed centres of medical genetics linked to university hospitals. These centres of genetics provide comprehensive genetic services which include, in addition to genetic tests, genetic counselling and moral support. These services are accessible to all residents in Belgium through coverage by the social security. PND has become a widely accepted procedure by the public and the health professionals, and has achieved significant prevention of birth defects, mainly chromosome abnormalities. The main problems involved in PND in Belgium are (1) the lack of regulations about indications for PND and (2) insufficient education in medical genetics in medical schools. It is hoped that the basic organisation of PND in Belgium will prevail in the future, with the proposed improvements. PMID:9101172

  4. Diagnosis and treatment of dementia: 2. Diagnosis

    PubMed Central

    Feldman, Howard H.; Jacova, Claudia; Robillard, Alain; Garcia, Angeles; Chow, Tiffany; Borrie, Michael; Schipper, Hyman M.; Blair, Mervin; Kertesz, Andrew; Chertkow, Howard

    2008-01-01

    Background Dementia can now be accurately diagnosed through clinical evaluation, cognitive screening, basic laboratory evaluation and structural imaging. A large number of ancillary techniques are also available to aid in diagnosis, but their role in the armamentarium of family physicians remains controversial. In this article, we provide physicians with practical guidance on the diagnosis of dementia based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, held in March 2006. Methods We developed evidence-based guidelines using systematic literature searches, with specific criteria for study selection and quality assessment, and a clear and transparent decision-making process. We selected studies published from January 1996 to December 2005 that pertained to key diagnostic issues in dementia. We graded the strength of evidence using the criteria of the Canadian Task Force on Preventive Health Care. Results Of the 1591 articles we identified on all aspects of dementia diagnosis, 1095 met our inclusion criteria; 620 were deemed to be of good or fair quality. From a synthesis of the evidence in these studies, we made 32 recommendations related to the diagnosis of dementia. There are clinical criteria for diagnosing most forms of dementia. A standard diagnostic evaluation can be performd by family physicians over multiple visits. It involves a clinical history (from patient and caregiver), a physical examination and brief cognitive testing. A list of core laboratory tests is recommended. Structural imaging with computed tomography or magnetic resonance imaging is recommended in selected cases to rule out treatable causes of dementia or to rule in cerebrovascular disease. There is insufficient evidence to recommend routine functional imaging, measurement of biomarkers or neuropsychologic testing. Interpretation The diagnosis of dementia remains clinically integrative based on history, physical examination and brief cognitive testing. A number of core laboratory tests are also recommended. Structural neuroimaging is advised in selected cases. Other diagnostic approaches, including functional neuroimaging, neuropsychological testing and measurement of biomarkers, have shown promise but are not yet recommended for routine use by family physicians. PMID:18362376

  5. SOYBEAN GENETICS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybean genetics is a broad area encompassing all aspects, such as qualitative genetics, molecular genetics, etc. The objective of this book chapter, a revision of a 1998 book on soybean, was to include information that could be used for soybean improvement, and to summarize the current status of s...

  6. Imaging Genetics

    ERIC Educational Resources Information Center

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

    2009-01-01

    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.

  7. Soybean Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybean genetics is a broad area encompassing all aspects, such as qualitative genetics, molecular genetics, etc. The objective of this book chapter was to include information that could be used for soybean improvement, and to summarize the current status of soybean genomics. Soybean germplasm is ...

  8. Genetic Evaluation of Short Stature

    PubMed Central

    Rosenfeld, Ron G.

    2014-01-01

    Context: Genetics plays a major role in determining an individual's height. Although there are many monogenic disorders that lead to perturbations in growth and result in short stature, there is still no consensus as to the role that genetic diagnostics should play in the evaluation of a child with short stature. Evidence Acquisition: A search of PubMed was performed, focusing on the genetic diagnosis of short stature as well as on specific diagnostic subgroups included in this article. Consensus guidelines were reviewed. Evidence Synthesis: There are a multitude of rare genetic causes of severe short stature. There is no high-quality evidence to define the optimal approach to the genetic evaluation of short stature. We review genetic etiologies of a number of diagnostic subgroups and propose an algorithm for genetic testing based on these subgroups. Conclusion: Advances in genomic technologies are revolutionizing the diagnostic approach to short stature. Endocrinologists must become facile with the use of genetic testing in order to identify the various monogenic disorders that present with short stature. PMID:24915122

  9. Shingles: Diagnosis, Treatment, and Outcome

    MedlinePLUS

    ... 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 ...

  10. Irritable bowel syndrome: Diagnosis and pathogenesis

    PubMed Central

    El-Salhy, Magdy

    2012-01-01

    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

  11. GENETIC CAUSES OF DILATED CARDIOMYOPATHY

    PubMed Central

    Mestroni, Luisa; Brun, Francesca; Spezzacatene, Anita; Sinagra, Gianfranco; Taylor, Matthew RG

    2014-01-01

    Dilated cardiomyopathy is a disease of the myocardium characterized by left ventricular dilatation and/or dysfunction, affecting both adult and pediatric populations. Almost half of cases are genetically determined with an autosomal pattern of inheritance. Up to 40 genes have been identified affecting proteins of a wide variety of cellular structures such as the sarcomere, the nuclear envelope, the cytoskeleton, the sarcolemma and the intercellular junction. Novel gene mutations have been recently identified thanks to advances in next-generation sequencing technologies. Genetic screening is an essential tool for early diagnosis, risk assessment, prognostic stratification and, possibly, adoption of primary preventive measures in affected patients and their asymptomatic relatives. The purpose of this article is to review the genetic basis of DCM, the known genotype-phenotype correlations, the role of current genetic sequencing techniques in the discovery of novel pathogenic gene mutations and new therapeutic perspectives. PMID:25584016

  12. Approach to the diagnosis of congenital myopathies.

    PubMed

    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

    2014-02-01

    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

  13. Diagnosis of Osteoporosis.

    ERIC Educational Resources Information Center

    Wahner, H. W.

    1987-01-01

    Early recognition of osteoporosis is difficult because symptoms are lacking and there are no distinct, readily accessible diagnostic features. This article reviews the standard approach, radiographic and laboratory diagnosis, bone mass measurement techniques, and interpretation of bone mineral data. (MT)

  14. Coronavirus Diagnosis and Treatment

    MedlinePLUS

    ... Read more information on enabling JavaScript. Skip Content Marketing Share this: Main Content Area Coronaviruses Diagnosis and Treatment Laboratory tests can detect human coronavirus infection. There are ...

  15. Amblyopia: Lazy Eye Diagnosis

    MedlinePLUS

    ... Eyelid Lump Feel Something in Eye Flashes of Light Irritation Itchiness Light Sensitivity Red Eye Reduced Vision Tearing See all ... lazy eye? Featured Video The Scary Drive that Led to a Diabetes Diagnosis Find An Eye M. ...

  16. [Cluster headache differential diagnosis].

    PubMed

    Guégan-Massardier, Evelyne; Laubier, Cécile

    2015-11-01

    Cluster headache is characterized by disabling stereotyped headache. Early diagnosis allows appropriate treatment, unfortunately diagnostic errors are frequent. The main differential diagnoses are other primary or essential headaches. Migraine, more frequent and whose diagnosis is carried by excess, trigeminal neuralgia or other trigemino-autonomic cephalgia. Vascular or tumoral underlying condition can mimic cluster headache, neck and brain imaging is recommended, ideally MRI. PMID:26549687

  17. [Diagnosis of sleep apnea].

    PubMed

    Kesper, Karl; Cassel, Werner; Hildebrandt, Olaf; Koehler, Ulrich

    2016-01-01

    Obstructive sleep apnea (OSA) is a clinically significant condition associated with an increase in cardiovascular risk, daytime sleepiness and in risk of accidents. Diagnosis usually relies on a detailed anamnesis and an ambulatory nocturnal polygraphy. Suspecting the presence of OSA or a persisting unclear daytime sleepiness in need of treatment further polysomnographic diagnosis should be performed in a specialized sleep center. Cardiorespiratory polysomnography is the diagnostic gold standard in differentiating sleep-related breathing and movement disorders. PMID:26710202

  18. who . . .GENETIC ASSOCIATION OF

    E-print Network

    Berdichevsky, Victor

    who . . .GENETIC ASSOCIATION OF COUNSELING DIRECTORS ROGRAMP are genetic counselors ? Genetic, medical genetics, epidemiological principles, and counseling theory with their skills in genetic risk to disease." The process of genetic counseling ". . . integrates the following: interpretation of family

  19. Genetics Home Reference: X-linked congenital stationary night blindness

    MedlinePLUS

    ... disorder catalog Conditions > X-linked congenital stationary night blindness On this page: Description Genetic changes Inheritance Diagnosis ... 2009 What is X-linked congenital stationary night blindness? X-linked congenital stationary night blindness is a ...

  20. Genetics Home Reference: Spinal muscular atrophy with progressive myoclonic epilepsy

    MedlinePLUS

    ... 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- ...

  1. Fibromyalgia Syndrome: Etiology, Pathogenesis, Diagnosis, and Treatment

    PubMed Central

    Bellato, Enrico; Marini, Eleonora; Castoldi, Filippo; Barbasetti, Nicola; Mattei, Lorenzo; Bonasia, Davide Edoardo; Blonna, Davide

    2012-01-01

    Fibromyalgia syndrome is mainly characterized by pain, fatigue, and sleep disruption. The etiology of fibromyalgia is still unclear: if central sensitization is considered to be the main mechanism involved, then many other factors, genetic, immunological, and hormonal, may play an important role. The diagnosis is typically clinical (there are no laboratory abnormalities) and the physician must concentrate on pain and on its features. Additional symptoms (e.g., Raynaud's phenomenon, irritable bowel disease, and heat and cold intolerance) can be associated with this condition. A careful differential diagnosis is mandatory: fibromyalgia is not a diagnosis of exclusion. Since 1990, diagnosis has been principally based on the two major diagnostic criteria defined by the ACR. Recently, new criteria have been proposed. The main goals of the treatment are to alleviate pain, increase restorative sleep, and improve physical function. A multidisciplinary approach is optimal. While most nonsteroidal anti-inflammatory drugs and opioids have limited benefit, an important role is played by antidepressants and neuromodulating antiepileptics: currently duloxetine (NNT for a 30% pain reduction 7.2), milnacipran (NNT 19), and pregabalin (NNT 8.6) are the only drugs approved by the US Food and Drug Administration for the treatment of fibromyalgia. In addition, nonpharmacological treatments should be associated with drug therapy. PMID:23213512

  2. [Microbiological diagnosis of viral respiratory infections].

    PubMed

    Eiros, José M; Ortiz de Lejarazu, Raúl; Tenorio, Alberto; Casas, Inmaculada; Pozo, Francisco; Ruiz, Guillermo; Pérez-Breña, Pilar

    2009-03-01

    Acute respiratory infection is the most common disease occurring over a person's lifetime, with etiological variations determined mainly by age, environmental circumstances, the healthcare setting, and the underlying pathology. More than 200 different viruses distributed in six viral families have been implicated in the pathogenesis of respiratory tract infection. These facts are generating an increasing diagnostic demand that should be incorporated into the healthcare setting without delay. To meet this demand, the Spanish Society of Infectious Diseases and Clinical Microbiology has updated its Standard Procedure for the microbiological diagnosis of viral respiratory infection. This document contains an update primarily of infections caused by influenza viruses, and secondarily, infections due to other conventional and emerging respiratory viruses. In all cases, the methods for direct virological diagnosis (cell culture, and detection of antigens and nucleic acid) are reviewed, with special reference to techniques for molecular detection and genetic characterization. PMID:19306718

  3. Advances in gene technology: Human genetic disorders

    SciTech Connect

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

    1984-01-01

    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.

  4. Genetic barcodes

    DOEpatents

    Weier, Heinz -Ulrich G

    2015-08-04

    Herein are described multicolor FISH probe sets termed "genetic barcodes" targeting several cancer or disease-related loci to assess gene rearrangements and copy number changes in tumor cells. Two, three or more different fluorophores are used to detect the genetic barcode sections thus permitting unique labeling and multilocus analysis in individual cell nuclei. Gene specific barcodes can be generated and combined to provide both numerical and structural genetic information for these and other pertinent disease associated genes.

  5. Clinical Genetic Testing of Periodic Fever Syndromes

    PubMed Central

    Marcuzzi, Annalisa; Piscianz, Elisa; Kleiner, Giulio; Tommasini, Alberto; Severini, Giovanni Maria; Monasta, Lorenzo; Crovella, Sergio

    2013-01-01

    Periodic fever syndromes (PFSs) are a wide group of autoinflammatory diseases. Due to some clinical overlap between different PFSs, differential diagnosis can be a difficult challenge. Nowadays, there are no universally agreed recommendations for most PFSs, and near half of patients may remain without a genetic diagnosis even after performing multiple-gene analyses. Molecular analysis of periodic fevers' causative genes can improve patient quality of life by providing early and accurate diagnosis and allowing the administration of appropriate treatment. In this paper we focus our discussion on effective usefulness of genetic diagnosis of PFSs. The aim of this paper is to establish how much can the diagnostic system improve, in order to increase the success of PFS diagnosis. The mayor expectation in the near future will be addressed to the so-called next generation sequencing approach. Although the application of bioinformatics to high-throughput genetic analysis could allow the identification of complex genotypes, the complexity of this definition will hardly result in a clear contribution for the physician. In our opinion, however, to obtain the best from this new development a rule should always be kept well in mind: use genetics only to answer specific clinical questions. PMID:23484126

  6. Genetic counseling 

    E-print Network

    Stough, Laura

    2014-01-01

    if they are carriers for Tay Sachs, cystic fibrosis, or Huntington’s disease. Encyclopedia of Special Education, edited by Cecil R. Reynolds, Kimberly J. Vannest, and Elaine Fletcher-Janzen. CopyrightC 2013 John Wiley & Sons, Inc. Ethics and Genetic Counseling Genetic....EuroGentest Network of Excellence Project. Retrieved from http://www.eurogentest.org/web/files/public/unit3/Definitions GeneticTesting-3rdDraf18Jan07.pdf Zych, K. A. (2008). Genetic counseling. In E. Fletcher-Janzen & C. R. Reynolds (Eds.), Encyclopedia of special...

  7. Diagnosis of childhood cancer.

    PubMed

    Raab, Christopher P; Gartner, J Carlton

    2009-12-01

    Childhood cancer is uncommon but remains the leading cause of disease-related death in children. Symptoms are often vague or insidious; they may suggest a more common alternative diagnosis, and they are quite different from those associated with adult malignancy. The skilled office practitioner must consider cancer as a diagnosis when symptoms/signs persist or when multiple symptoms point toward a possible diagnosis of malignancy. Early diagnosis is critical, as survival rates have increased dramatically over the past decades. Prolonged delay in diagnosis is common, especially for brain tumors and certain lymphomas (Hodgkin disease). When one encounters symptoms suspicious for a childhood malignancy, it is imperative that the child be referred to a pediatric cancer center. These centers possess not only the ability to further evaluate and manage children with malignancy, but also are able to provide support for patients and their families. This evaluation may include further imaging, but often involves obtaining tissue for histologic review. This will require appropriate tumor or bone marrow biopsy, preferably before the start of treatment. Depending upon the type of suspected malignancy, direct tumor biopsy can be facilitated by imaging-guided biopsy (ultrasound, CT, or MRI), which spares the patient additional surgery. This optimally is performed by a skilled team: hematologist/oncologist, surgeon, radiologist, and pathologist. Best results depend upon early referral by the thoughtful practitioner. PMID:19913181

  8. Diagnosis and Metaphor.

    PubMed

    Hanne, Michael

    2015-01-01

    Human beings rely on metaphor as a primary cognitive device for interpreting the world around them. Metaphors figure especially strongly in discourse around health, illness, and medicine. It is not just that patients use metaphors to describe their personal experience of being unwell, or that medical professionals employ metaphor to convey a diagnosis, describe a treatment, or explain the function of an organ to their patients. Metaphor, it is argued, lies at the heart of the process of diagnosis. Moreover, diagnosticians employ competing metaphors in the early stages of diagnosis to speculate on alternative ways of viewing a puzzling set of symptoms. Diagnosis is often defined as a process of ordering and classifying, while metaphor is a device for playing with classifications. The medical systems of different cultures depend on different sets of fundamental metaphors. Modern Western biomedicine is organized around a series of basic metaphors: the body as machine, the body as the site of battle, and the body as a communication system. Traditional Chinese medicine, on the other hand, uses images of flow and blockage, balance and imbalance, and works by analogy with five elements: wood, fire, earth, metal, and water. Psychologists are sometimes able to detect from a patient's own use of metaphor, or inability to use or recognize metaphor, clues to a diagnosis of psychosis or autism. With conditions such as anorexia nervosa, therapists may actually work to modify the dysfunctional metaphors by which patients depict themselves, with the purpose of establishing positive metaphors for envisaging recovery. PMID:26657680

  9. Eugenic selection benefits embryos.

    PubMed

    Walker, Mark

    2014-06-01

    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

  10. 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

    Bathke, K.; Liehr. T.; Ekici, A.

    1994-09-01

    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.

  11. Prenatal diagnosis and the trouble with eugenics.

    PubMed

    Landeweerd, Laurens

    2009-01-01

    In the past few years we have witnessed huge steps forwards in reproductive technology. Specifically genetic diagnosis has created a range of possibilities. This carries along benefits for prenatal care as well as carrying along unprecedented ethical dilemmas that demonstrate some more problematic sides of several basic notions in medical ethics. These new technologies also led to a widespread public ethical debate on the desirability of these technologies. Concerns are felt specifically with the potential eugenic application of these technologies. To have a correct overview of the possibilities to a new eugenics, one needs to explore the actual developments in the field of human genetics in recent years. This is important to avoid deviating from what is actually occurring into the realm of science fiction. PMID:19860341

  12. Syncope: diagnosis and management.

    PubMed

    Walsh, Kathleen; Hoffmayer, Kurt; Hamdan, Mohamed H

    2015-02-01

    Syncope is defined as transient loss of consciousness due to global cerebral hypoperfusion. It is characterized by having a relatively rapid onset, brief duration with spontaneous and full recovery. The major challenge in the evaluation of patients with syncope is that most patients are asymptomatic at the time of their presentation. A thorough history and physical examination including orthostatic assessment are crucial for making the diagnosis. After initial evaluation, short-term risk assessment should be performed to determine the need for admission. If the short-term risk is high, inpatient evaluation is needed. If the short-term risk is low, outpatient evaluation is recommended. In patients with suspected cardiac syncope, monitoring is indicated until a diagnosis is made. In patients with suspected reflex syncope or orthostatic hypotension, outpatient evaluation with tilt-table testing is appropriate. Syncope units have been shown to improve the rate of diagnosis while reducing cost and thus are highly recommended. PMID:25686850

  13. Diagnosis of hepatocellular carcinoma

    PubMed Central

    Di Bisceglie, Adrian M.

    2005-01-01

    Hepatocellular carcinoma (HCC) is responsible for a large proportion of cancer deaths worldwide. HCC is frequently diagnosed after the development of clinical deterioration at which time survival is measured in months. Long-term survival requires detection of small tumors, often present in asymptomatic individuals, which may be more amenable to invasive therapeutic options. Surveillance of high-risk individuals for HCC is commonly performed using the serum marker alfa-fetoprotein (AFP) often in combination with ultrasonography. Various other serologic markers are currently being tested to help improve surveillance accuracy. Diagnosis of HCC often requires more sophisticated imaging modalities such as CT scan and MRI, which have multiphasic contrast enhancement capabilities. Serum AFP used alone can be helpful if levels are markedly elevated, which occurs in fewer than half of cases at time of diagnosis. Confirmation by liver biopsy can be performed under circumstances when the diagnosis of HCC remains unclear. PMID:18333158

  14. Human prenatal diagnosis

    SciTech Connect

    Filkins, K.; Russo, R.J.

    1985-01-01

    The multiauthor text is written as a ''guide to rationalize and clarify certain aspects of diagnosis, general counseling and intervention'' for ''health professionals who provide care to pregnant women.'' The text is not aimed at the ultrasonographer but rather at the physicians who are clinically responsible for patient management. Chapters of relevance to radiologists include an overview of prenatal screening and counseling, diagnosis of neural tube defects, ultrasonographic (US) scanning of fetal disorders in the first and second trimesters of pregnancy, US scanning in the third trimester, multiple gestation and selective termination, fetal echo and Doppler studies, and fetal therapy. Also included are overviews of virtually all currently utilized prenatal diagnostic techniques including amniocentesis, fetal blood sampling, fetoscopy, recombinant DNA detection of hemoglobinopathies, chorionic villus sampling, embryoscopy, legal issues, and diagnosis of Mendelian disorders by DNA analysis.

  15. Remote diagnosis server

    NASA Technical Reports Server (NTRS)

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

    2004-01-01

    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.

  16. Genetics of Epilepsy in Clinical Practice

    PubMed Central

    2015-01-01

    Genetics should now be part of everyday clinical epilepsy practice. Good data exist to provide empiric risks based on epilepsy syndrome diagnosis. Investigation of the molecular basis of some epilepsies is now a practical clinical task and is of clear value to the patient and family. In some cases, specific therapeutic decisions can now be made based on genetic findings, and this scenario of precision therapy is likely to increase in the coming years. PMID:26316866

  17. Carpal tunnel syndrome diagnosis.

    PubMed

    Sucher, Benjamin M; Schreiber, Adam L

    2014-05-01

    Carpal tunnel syndrome (CTS) is a common median nerve compression syndrome and the most common peripheral mononeuropathy. The clinical syndrome is diagnosed by history and physical examination. Electrodiagnostic testing is the objective method used to measure median nerve dysfunction at the wrist and confirm the clinical diagnosis of CTS. Neuromuscular ultrasound imaging of the carpal tunnel provides supportive diagnostic information by revealing pathologic nerve swelling in CTS, and other anatomic anomalies that compress the median nerve. These tests cannot be used to make the diagnosis in the absence of history that includes CTS symptom criteria and excludes other causes. PMID:24787330

  18. Pythium Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This is a book chapter on the genetics of Pythium to be published in a book titled "Oomycete Genetics and Genomics: Biology, Interactions with Plants and Animals, and Toolbox." It covers the basic taxonomic classification of species in the genus, the phylogenetic placements, and reviews the literatu...

  19. Genetic Engineering

    ERIC Educational Resources Information Center

    Phillips, John

    1973-01-01

    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)

  20. NEW DEVELOPMENTS IN THE DIAGNOSIS AND TREATMENT OF THYROID CANCER

    PubMed Central

    Schneider, David F.; Chen, Herbert

    2013-01-01

    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

  1. Lymphangioleiomyomatosis: differential diagnosis and optimal management

    PubMed Central

    Xu, Kai-Feng; Lo, Bee Hong

    2014-01-01

    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

  2. Lymphangioleiomyomatosis: differential diagnosis and optimal management.

    PubMed

    Xu, Kai-Feng; Lo, Bee Hong

    2014-01-01

    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

  3. Genetic neurological channelopathies: molecular genetics and clinical phenotypes.

    PubMed

    Spillane, J; Kullmann, D M; Hanna, M G

    2016-01-01

    Evidence accumulated over recent years has shown that genetic neurological channelopathies can cause many different neurological diseases. Presentations relating to the brain, spinal cord, peripheral nerve or muscle mean that channelopathies can impact on almost any area of neurological practice. Typically, neurological channelopathies are inherited in an autosomal dominant fashion and cause paroxysmal disturbances of neurological function, although the impairment of function can become fixed with time. These disorders are individually rare, but an accurate diagnosis is important as it has genetic counselling and often treatment implications. Furthermore, the study of less common ion channel mutation-related diseases has increased our understanding of pathomechanisms that is relevant to common neurological diseases such as migraine and epilepsy. Here, we review the molecular genetic and clinical features of inherited neurological channelopathies. PMID:26558925

  4. Laboratory Diagnosis of Pertussis.

    PubMed

    van der Zee, Anneke; Schellekens, Joop F P; Mooi, Frits R

    2015-10-01

    The introduction of vaccination in the 1950s significantly reduced the morbidity and mortality of pertussis. However, since the 1990s, a resurgence of pertussis has been observed in vaccinated populations, and a number of causes have been proposed for this phenomenon, including improved diagnostics, increased awareness, waning immunity, and pathogen adaptation. The resurgence of pertussis highlights the importance of standardized, sensitive, and specific laboratory diagnoses, the lack of which is responsible for the large differences in pertussis notifications between countries. Accurate laboratory diagnosis is also important for distinguishing between the several etiologic agents of pertussis-like diseases, which involve both viruses and bacteria. If pertussis is diagnosed in a timely manner, antibiotic treatment of the patient can mitigate the symptoms and prevent transmission. During an outbreak, timely diagnosis of pertussis allows prophylactic treatment of infants too young to be (fully) vaccinated, for whom pertussis is a severe, sometimes fatal disease. Finally, reliable diagnosis of pertussis is required to reveal trends in the (age-specific) disease incidence, which may point to changes in vaccine efficacy, waning immunity, and the emergence of vaccine-adapted strains. Here we review current approaches to the diagnosis of pertussis and discuss their limitations and strengths. In particular, we emphasize that the optimal diagnostic procedure depends on the stage of the disease, the age of the patient, and the vaccination status of the patient. PMID:26354823

  5. What Makes Diagnosis Hard?

    ERIC Educational Resources Information Center

    Wears, Robert L.

    2009-01-01

    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…

  6. DIAGNOSIS OF BOVINE NEOSPOROSIS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The protozoan parasite Neospora caninum is a major cause of abortion in cattle. The diagnosis of neosporosis-associated mortality and abortion in cattle is difficult. In the present papers we review histologic, serologic, immunohistochemical, and molecular methods for dignosis of bovine neosporosis....

  7. Diagnosis of Hearing Loss.

    ERIC Educational Resources Information Center

    World Federation of the Deaf, Rome (Italy).

    Seven conference papers from the U.S.S.R., India, Poland, Czechoslovakia, and Yugoslavia consider the diagnosis of hearing loss. They are "Examination of Hearing of Children, Aged from 2 to 5, by Means of Playing Audiometry" by A. P. Kossacheva, "A Study of the Etiology and Pattern of Deafness in a School for the Deaf in Madras, South India" by Y.…

  8. Multi-Disciplinary Diagnosis.

    ERIC Educational Resources Information Center

    Schiffman, Gilbert B.

    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…

  9. Diagnosis of hepatocellular carcinoma

    PubMed Central

    Gomaa, Asmaa I; Khan, Shahid A; Leen, Edward LS; Waked, Imam; Taylor-Robinson, Simon D

    2009-01-01

    Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the diagnosis of HCC, including serum markers, radiological techniques and histological evaluation, and summarises international guidelines for the diagnostic approach to HCC. PMID:19294759

  10. Prenatal diagnosis: whose right?

    PubMed Central

    Heyd, D

    1995-01-01

    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

  11. Genetics Home Reference: What is genetic testing?

    MedlinePLUS

    ... Precision Medicine Next Handbook > Genetic Testing > What is genetic testing? Genetic testing is a type of medical ... emotional aspects of testing. For general information about genetic testing: MedlinePlus offers a list of links to ...

  12. New insights on taxonomy, phylogeny and population genetics of Leishmania (Viannia) parasites based on multilocus sequence analysis.

    PubMed

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

    2012-01-01

    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

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

    E-print Network

    Martin, Ralph R.

    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

  14. [The electrophysiologic diagnosis for muscle ion channelopathies].

    PubMed

    Arimura, Yumiko; Nakamura, Tomonori; Yoshimura, Michiyoshi; Uehara, Akiko; Arimura, Kimiyoshi; Sakoda, Shin-Ichi; Takashima, Hiroshi

    2012-01-01

    The periodic paralysis (PP) and myotonic syndromes have been recognized as muscle ion channelopathies (MIC) consequent to the discovery of genetic abnormalities of muscle ion channels. Genetic studies are therefore indispensable in the diagnosis of MIC. However, it is not practical to examine all muscle ion channels immediately upon identification of clinical symptoms. Clinical symptoms of MIC occur due to the abnormal excitability of the muscle membrane which is in turn related to abnormal ion channel genes. Therefore, a series of electrophysiologic tests is useful in examining the characteristics of abnormal excitability and predicting the abnormal ion channel Needle EMG studies can detect myotonic discharges while the prolonged exercise test can distinguish between primary and secondary PP. For myotonia, pattern I which includes the repeated short exercise test at room temperature or at cold skin temperature is specific for paramyotonia congenita, pattern II is characteristic for myotonia congenita, and pattern III is useful for Na channel myotonia. The decrement of CMAP with 10 Hz repetitive stimulation is related to mutation type in myotonia congenita. Thus, these electrophysiological tests may be of use in screening for MIC to narrow down the diagnosis and the selection of candidates for gene analysis. PMID:23196580

  15. Timely diagnosis and treatment essential in glomerulonephritis.

    PubMed

    Lewis, Gareth; Maxwell, Alexander P

    2015-02-01

    Glomerulonephritis is an important cause of kidney disease and, in the UK, the most common diagnosis in patients receiving chronic dialysis or waiting for kidney transplantation. A key feature is the presence of urinary abnormalities (proteinuria ± haematuria). Patients with nephrotic syndrome typically present with peripheral oedema, massive urinary protein loss and associated low serum albumin levels. Blood pressure and renal function, as measured by eGFR, are usually normal initially. Patients presenting with nephritic syndrome tend to be hypertensive with dipstick-positive or visible haematuria. There may be rapidly progressive renal dysfunction and fall in eGFR. Many patients will have a background genetic susceptibility to glomerulonephritis which may be triggered by environmental, infective or autoimmune factors. Autoimmunity, in combination with genetic factors, is responsible for a significant proportion of cases of glomerulonephritis. Infective agents such as viruses can precipitate minimal change disease. NSAIDs, lithium, penicillamine and heroin can cause nephrotic syndrome. Timely diagnosis and treatment of glomerulonephritis can help to minimise both the occurrence and severity of complications. All patients with glomerulonephritis should be managed according to CKD guidelines with CKD stage-appropriate measurement of renal function, blood pressure, and proteinuria. PMID:25816500

  16. Biology 4250 Evolutionary Genetics

    E-print Network

    Innes, David J.

    clones of genetically identical individuals Facultative sexual/asexual sexual + vegetative reproduction connections among more distantly related taxa Human Forensics Ramets and Genets (sexual and asexual) Genetic chimeras * Genetic chimeras Gender ascertainment Genetic parentage * *More detail Sexual reproduction

  17. Genetics and celiac disease: the importance of screening.

    PubMed

    Leonard, Maureen M; Serena, Gloria; Sturgeon, Craig; Fasano, Alessio

    2015-02-01

    The prevalence of celiac disease (CD) is increasing. Despite an increased awareness and an improvement in diagnostic testing, the majority of individuals with CD remain undiagnosed. Currently, genetic testing in screening for CD is used only to exclude a diagnosis or reinforce a strong clinical suspicion. In this paper, we review the most current literature regarding genetic testing in CD. In response to important data revealing that an individual's HLA haplotype is one of the strongest known predictors of CD, we propose genetic screening for at-risk infants to stratify individuals based on genetic risk to ultimately create genetic specific screening algorithms. PMID:25294637

  18. Bedbugs: Diagnosis, Treatment, and Outcome

    MedlinePLUS

    ... Diseases and treatments A - D Bedbugs Diagnosis, treatment Bedbugs: Diagnosis, treatment, and outcome Bedbug bites: When bedbugs ... pattern. How do you know if you have bedbugs? To find out if you have bedbugs, you ...

  19. Chronic Fatigue Syndrome (CFS): Diagnosis

    MedlinePLUS

    ... CDC.gov . Chronic Fatigue Syndrome (CFS) Share Compartir Diagnosis Diagnostic Challenges For doctors, diagnosing chronic fatigue syndrome ( ... severity. These factors have contributed to a low diagnosis rate. Of the one to four million Americans ...

  20. Pneumocystis Pneumonia Diagnosis and Testing

    MedlinePLUS

    ... CDC.gov . Fungal Diseases Share Compartir Pneumocystis pneumonia Diagnosis and Testing P. jirovecii cysts in a smear ... Aspergillosis Definition Symptoms People at Risk & Prevention Sources Diagnosis & Testing Treatment Health Professionals Statistics More Resources Blastomycosis ...

  1. Pneumococcal Disease Diagnosis and Treatment

    MedlinePLUS

    ... Health Organization National Foundation for Infectious Diseases Sepsis Diagnosis and Treatment Recommend on Facebook Tweet Share Compartir ... pneumococcal disease, antibiotics can help prevent severe illness. Diagnosis If invasive pneumococcal disease , like meningitis or bloodstream ...

  2. Inclusion-Body Myositis: Diagnosis

    MedlinePLUS

    ... Progress 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 ...

  3. TBI Symptoms, Diagnosis, Treatment, Prevention

    MedlinePLUS

    ... Issues Cover Story: Traumatic Brain Injury TBI Symptoms, Diagnosis, Treatment, Prevention Past Issues / Fall 2008 Table of ... of coordination, and increased confusion, restlessness or agitation. Diagnosis Imaging tests, including X-rays of the head ...

  4. Genetic Alliance

    MedlinePLUS

    ... form Search About Us Council Staff Jobs and Internships Press Releases Annual Reports Archives & History Sign Up ... Main menu About Us - Council - Staff - Jobs and Internships - Press Releases - Annual Reports - Archives & History -- Introduction -- Genetic ...

  5. RNA genetics

    SciTech Connect

    Domingo, E. ); Holland, J.J. . Dept. of Biology); Ahlquist, P. . Dept. of Plant Pathology)

    1988-01-01

    This book contains the proceedings on RNA genetics: Retroviruses, Viroids, and RNA recombination, Volume 2. Topics covered include: Replication of retrovirus genomes, Hepatitis B virus replication, and Evolution of RNA viruses.

  6. Genetic Testing

    MedlinePLUS

    ... 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 ...

  7. Prenatal Diagnosis of Antley-Bixler Syndrome and POR Deficiency

    PubMed Central

    Oldani, Elena; Garel, Catherine; Bucourt, Martine; Carbillon, Lionel

    2015-01-01

    Patient: Female, fetus Final Diagnosis: Antley-Bixler syndrome Symptoms: Craniosynostosis • midface hypoplasia • femoral bowing • radiohumeral synostosis Medication: None Clinical Procedure: Prenatal diagnosis of severe fetal bone disease using detailed ultrasonography and computed tomography Specialty: Obstetrics and Gynecology • Maternal-Fetal Medicine Objective: Rare disease Background: Prenatal diagnosis of severe bone diseases is challenging and requires complete and precise analysis of fetal anomalies to guide genetic investigation and parental counselling. Case Report: We report a rare case of Antley-Bixler syndrome prenatally diagnosed at 26 weeks’ gestation by ultrasound and computed tomography in a 28-year-old woman with a history of early termination of pregnancy for “malposition of the inferior limbs”. The prenatal ultrasound scan showed severe femoral bowing and frontal bossing. Taking into account the high probability of a recurrent severe skeletal disorder, a computed tomography (CT) scan was proposed. CT findings revealed bilateral femora deformation, craniosynostosis, severe midface hypoplasia, and radiohumeral synostosis. These anomalies strongly suggested Antley-Bixler syndrome. Sequencing of the POR gene in the fetus and the parents revealed compound heterozygous mutations in exon 9 and intron 7, both inherited from each parent, and this finding allowed genetic counseling. Conclusions: The first step in the proper prenatal diagnosis of fetal bone disorders is the precise analysis of ultrasonographic images. However, when a severe fetal inherited disorder is strongly suspected in late mid-trimester, CT may be discussed and usefully contribute to diagnosis and prognosis assessment. PMID:26670660

  8. Ciona Genetics

    PubMed Central

    Veeman, Michael T.; Chiba, Shota; Smith, William C.

    2010-01-01

    Ascidians, such as Ciona, are invertebrate chordates with simple embryonic body plans and small, relatively non-redundant genomes. Ciona genetics is in its infancy compared to many other model systems, but it provides a powerful method for studying this important vertebrate outgroup. Here we give basic methods for genetic analysis of Ciona, including protocols for controlled crosses both by natural spawning and by the surgical isolation of gametes; the identification and propagation of mutant lines; and strategies for positional cloning. PMID:21805273

  9. Proteinticle engineering for accurate 3D diagnosis.

    PubMed

    Lee, Jong-Hwan; Seo, Hyuk Seong; Song, Jong Am; Kwon, Koo Chul; Lee, Eun Jung; Kim, Ho Jin; Lee, Eun Bong; Cha, Young Joo; Lee, Jeewon

    2013-12-23

    In nature certain proteins are self-assembled inside cells to form nanoscale particles (named "proteinticles") with constant structure and surface topology. Unlike chemically synthesized nanomaterials (e.g., various metal, carbon, and polymer nanoparticles), a variety of functional proteinticles can be easily created through genetic modification of the proteinticle surface, i.e., by adding or inserting specified proteins/peptides to the N- or C-terminus or the internal region of the protein constituent. Here we present proteins/peptides that recognize disease-specific antibodies on the surface of human ferritin based proteinticles for accurate 3D diagnosis of human autoimmune and infectious diseases. The surface display of the extracellular domain of myelin oligodendrocyte glycoprotein (MOG) with native conformation successfully discriminated between autoantibodies to native or denatured MOG, leading to the reliable diagnosis of multiple sclerosis with enhanced accuracy. Also we simultaneously displayed different antigenic peptides from hepatitis C virus (HCV) on the same proteinticle surface with modulating the composition of each peptide. The proteinticles with the heterogeneous peptide surface detected anti-HCV antibodies in patient sera with 100% accuracy. The proposed method of proteinticle engineering can be applied in general to the sensitive and specific diagnosis of many other human diseases. PMID:24195532

  10. [Collaboration between child psychiatry and medical genetics. Genetic diseases with an atypical beginning].

    PubMed

    Brenot, M; Houdiard, C; Couillault, G; Nivelon, J L; Nivelon, A

    1989-01-01

    When a children psychiatrist, faced to atypical psychological troubles, comes up against difficulties in establishing a precise diagnosis, he may consider a genetic etiology and ask for a genetic consultation. He may encounter many problems when he suggests this specialized consultation to the parents. These have often been prepared for a long time to the necessity of a psychiatric therapy in order to cure their child's troubles. The geneticist's diagnosis will induce the parents and the psychiatrist to have a different look on the child and mostly will set limits to the possibilities of treatment. PMID:2715779

  11. An ACE diagnosis

    PubMed Central

    Nasher, Omar; Gupta, Anindya

    2013-01-01

    Gaucher's disease is not commonly considered in the differential diagnosis of adult patients with hepatosplenomegaly and increased serum ACE. A 19-year-old girl presented with recurrent epigastric and left hypochondrial pain over a period of 9?years, associated with episodes of nausea and diarrhoea. She was extensively investigated and found to have splenomegaly and raised serum ACE. A screen for haematological disorders was negative. She reported an insect bite during an overseas holiday preceding her symptoms. She was therefore also screened for infectious causes of hepatosplenomegaly but without success. Later on in life, she reported joint pain and discomfort. Sarcoidosis was thought to be the putative cause on more than one occasion. However, the presence of splenomegaly and her relatively young age, led the rheumatologist to the correct diagnosis. PMID:23417380

  12. Genetics of ischaemic stroke in young adults

    PubMed Central

    Terni, Eva; Giannini, Nicola; Brondi, Marco; Montano, Vincenzo; Bonuccelli, Ubaldo; Mancuso, Michelangelo

    2014-01-01

    Background Stroke may be a clinical expression of several inherited disorders in humans. Recognition of the underlined genetic disorders causing stroke is important for a correct diagnosis, for genetic counselling and, even if rarely, for a correct therapeutic management. Moreover, the genetics of complex diseases such the stroke, in which multiple genes interact with environmental risk factors to increase risk, has been revolutionized by the Genome-Wide Association Study (GWAS) approach. Scope of review Here we review the single-gene causes of ischemic stroke, bringing the reader from the candidate gene method toward the exciting new horizons of genetic technology. Major conclusions The aetiological diagnosis of ischemic stroke in young adults is more complex than in the elderly. The identification of a genetic cause is important to provide appropriate counseling and to start a correct therapy, when available. The advent of GWAS technology, such as for other complex pathological conditions, has contributed enormously to the understanding of many of these genetic bases. For success large, well phenotyped case cohorts are required, and international collaborations are essential. General significance This review focuses on the main causes of genetically-based ischemic stroke in young adults, often classified as indeterminate, investigating also the recent findings of the GWAS, in order to improve diagnostic and therapeutic management. PMID:26672892

  13. Molecular diagnosis of hypophosphatasia and differential diagnosis by targeted Next Generation Sequencing.

    PubMed

    Taillandier, Agnès; Domingues, Christelle; De Cazanove, Clémence; Porquet-Bordes, Valérie; Monnot, Sophie; Kiffer-Moreira, Tina; Rothenbuhler, Agnès; Guggenbuhl, Pascal; Cormier, Catherine; Baujat, Geneviève; Debiais, Françoise; Capri, Yline; Cohen-Solal, Martine; Parent, Philippe; Chiesa, Jean; Dieux, Anne; Petit, Florence; Roume, Joelle; Isnard, Monica; Cormier-Daire, Valérie; Linglart, Agnès; Millán, José Luis; Salles, Jean-Pierre; Muti, Christine; Simon-Bouy, Brigitte; Mornet, Etienne

    2015-11-01

    Hypophosphatasia (HPP) is a rare inherited skeletal dysplasia due to loss of function mutations in the ALPL gene. The disease is subject to an extremely high clinical heterogeneity ranging from a perinatal lethal form to odontohypophosphatasia affecting only teeth. Up to now genetic diagnosis of HPP is performed by sequencing the ALPL gene by Sanger methodology. Osteogenesis imperfecta (OI) and campomelic dysplasia (CD) are the main differential diagnoses of severe HPP, so that in case of negative result for ALPL mutations, OI and CD genes had often to be analyzed, lengthening the time before diagnosis. We report here our 18-month experience in testing 46 patients for HPP and differential diagnosis by targeted NGS and show that this strategy is efficient and useful. We used an array including ALPL gene, genes of differential diagnosis COL1A1 and COL1A2 that represent 90% of OI cases, SOX9, responsible for CD, and 8 potentially modifier genes of HPP. Seventeen patients were found to carry a mutation in one of these genes. Among them, only 10 out of 15 cases referred for HPP carried a mutation in ALPL and 5 carried a mutation in COL1A1 or COL1A2. Interestingly, three of these patients were adults with fractures and/or low BMD. Our results indicate that HPP and OI may be easily misdiagnosed in the prenatal stage but also in adults with mild symptoms for these diseases. PMID:26432670

  14. Culture and psychiatric diagnosis.

    PubMed

    Lewis-Fernández, Roberto; Aggarwal, Neil Krishan

    2013-01-01

    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

  15. [Diagnosis of maternofetal infections].

    PubMed

    Vauloup-Fellous, Christelle; Bouthry, Elise

    2015-06-01

    Prevention is an essential aspect of management of infections that can be transmitted from mother to fetus during pregnancy: The prescription and interpretation of serologic markers differ according to clinical context: screening, counts, clinical signs, or ultrasound signs. Testing for rubella IgG antibodies is recommended at the beginning of pregnancy, in the absence of written results proving either immunity or previous vaccination with two doses. Monthly serologic monitoring (IgG and IgM) is recommended for woman lacking immunity to toxoplasmosis. Diagnosis of a primary infection requires the concomitant detection of IgG and IgM. Nonetheless, the presence of specific IgM is not necessarily a marker of recent infection. IgG avidity must be measured to confirm or rule out a recent primary infection when IgM is positive. The observation of stable antibody titers is often inaccurately considered to be reassuring. In fact, depending on the individuals tested and especially the technique used, antibodies may reach a plateau several days or several weeks after the onset of the infection. Clinical diagnosis of rubella is not reliable, and its rarity today means that physicians are unlikely to recognize it or consider it as a possible differential diagnosis. Nonetheless, residual circulation of the rubella virus continues in France. A chickenpox rash is diagnosed clinically. For atypical eruptions, the virus can be sought directly in the vesicular fluid. Serology is not helpful in this case. PMID:26033555

  16. Epidemiology and diagnosis of lysosomal storage disorders; challenges of screening.

    PubMed

    Kingma, Sandra D K; Bodamer, Olaf A; Wijburg, Frits A

    2015-03-01

    The lysosomal storage disorders (LSDs) are a group of genetic disorders resulting from defective lysosomal metabolism and subsequent accumulation of substrates. Patients present with a large phenotypic spectrum of disease manifestations that are generally not specific for LSDs, leading to considerable diagnostic delay and missed cases. Introduction of new disease modifying therapies for LSDs has made early diagnosis a priority. Increased awareness, but particularly the introduction of screening programs allow for early diagnosis and timely initiation of treatment. This review will provide insight into the epidemiology and diagnostic process for LSDs. In addition, challenges for carrier screening, high-risk screening and newborn population screening for LSDs are discussed. PMID:25987169

  17. Counseling Psychology in the Era of Genetic Testing: Considerations for Practice, Research, and Training

    ERIC Educational Resources Information Center

    Kaut, Kevin P.

    2006-01-01

    The field of genetics and the process of testing for genetic disorders have advanced considerably over the past half century, ushering in significant improvements in certain areas of medical diagnosis and disease prediction. However, genetic discoveries are accompanied by many social, emotional, and psychological implications, and counseling…

  18. Genetic screening

    PubMed Central

    Andermann, Anne; Blancquaert, Ingeborg

    2010-01-01

    Abstract OBJECTIVE To provide a primer for primary care professionals who are increasingly called upon to discuss the growing number of genetic screening services available and to help patients make informed decisions about whether to participate in genetic screening, how to interpret results, and which interventions are most appropriate. QUALITY OF EVIDENCE As part of a larger research program, a wide literature relating to genetic screening was reviewed. PubMed and Internet searches were conducted using broad search terms. Effort was also made to identify the gray literature. MAIN MESSAGE Genetic screening is a type of public health program that is systematically offered to a specified population of asymptomatic individuals with the aim of providing those identified as high risk with prevention, early treatment, or reproductive options. Ensuring an added benefit from screening, as compared with standard clinical care, and preventing unintended harms, such as undue anxiety or stigmatization, depends on the design and implementation of screening programs, including the recruitment methods, education and counseling provided, timing of screening, predictive value of tests, interventions available, and presence of oversight mechanisms and safeguards. There is therefore growing apprehension that economic interests might lead to a market-driven approach to introducing and expanding screening before program effectiveness, acceptability, and feasibility have been demonstrated. As with any medical intervention, there is a moral imperative for genetic screening to do more good than harm, not only from the perspective of individuals and families, but also for the target population and society as a whole. CONCLUSION Primary care professionals have an important role to play in helping their patients navigate the rapidly changing terrain of genetic screening services by informing them about the benefits and risks of new genetic and genomic technologies and empowering them to make more informed choices. PMID:20393090

  19. [Practical genetic counseling conducted by clinical neurologist].

    PubMed

    Yoshida, Kunihiro

    2011-11-01

    With the increasing knowledge of the molecular bases for neurological disorders, neurologists are now often required to administer genetic testing and to present the resulting information effectively in clinical practice. In the neurologic clinical setting, genetic testing of affected individuals is usually taken into consideration for a correct diagnosis, but is rarely undertaken in healthy individuals to determine genetic risks for their life planning. Genetic counseling is indispensable for genetic testing because test results may cause serious distress for patients and their family members (referred to as "clients" in the counseling session). Genetic counseling is the medical process of communication that helps clients understand the nature of the genetic disorder and the options open to them in management and family planning. Through the counseling process, clients are given both the medical information and psychosocial support necessary for their own decision-making. Thus, the aim of genetic counseling is to support the client's decision-making process regarding genetic testing, and to avoid unfavorable actions after disclosure of test results. In the broad sense, genetic counseling is a part of ordinary clinical practice for patients with hereditary neurological disorders because neurologic clinical practice includes education and psychosocial support for patients. But clients seeking predictive genetic testing, which includes complicated ethical and psychosocial issues, should be referred to more specialized genetic counseling clinics that take a multi-disciplinary approach. The counseling process is not a one-way transmission of medical information by neurologists, but consists of two-way communication between patients and neurologists. It is therefore crucial for neurologists to master communication skills, particularly those involving active listening and empathic understanding, in order to conduct effective genetic counseling in clinical practice. PMID:22277396

  20. Dual Diagnosis: Substance Abuse and Mental Illness

    MedlinePLUS

    ... Mental Health Conditions Related Conditions Dual Diagnosis Dual Diagnosis Dual diagnosis is a term for when someone ... chemistry and behavior. How Common is a Dual Diagnosis? About a third of all people experiencing mental ...

  1. Genetic determinants of plasma triglycerides

    PubMed Central

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

    2011-01-01

    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

  2. Diagnosis of ADHD and its Behavioral, Neurologic and Genetic Roots

    PubMed Central

    Mueller, Kathryn L.; Tomblin, J. Bruce

    2014-01-01

    Attention-Deficit/Hyperactivity Disorder (ADHD) is a common developmental disorder often associated with other developmental disorders including speech, language, and reading disorders. Here we review the principal features of ADHD and current diagnostic standards for the disorder. We outline the ADHD subtypes, which are based upon the dimensions of inattention and hyperactivity. These serve as the phenotype for ADHD. Current nomenclature implies a deficit in the cognitive construct of attention, and this has taken researchers on an extended inquiry into several potential endophenotypes underlying ADHD, in particular executive function and its subcomponents. We review this literature and then delve into the neurobiology of ADHD. This research has suggested to us that the corticostriatal system is a strong candidate system in the etiology of ADHD, in part because of the dopaminergic system, which is known to play a role in the disorder. We present this system as an important contributor to the comorbidty of ADHD with other developmental disorders, especially language disorder. PMID:25506117

  3. Arsenicosis: diagnosis and treatment.

    PubMed

    Das, Nilay Kanti; Sengupta, Sujit Ranjan

    2008-01-01

    Diagnosis of arsenicosis relies on both clinical and laboratory criteria, but principally it can be diagnosed on the basis of its cutaneous manifestations. Cutaneous manifestations (melanosis, keratosis, and cutaneous cancers) are essential clues in the diagnosis, and trained dermatologists or arsenic experts are able to clinically confirm a case even without laboratory backup. Although systemic manifestations are not considered as diagnostic hallmarks, yet their presence serves as important telltale signs in arriving at the diagnosis. In countries where laboratory facilities are available, measuring the level of arsenic in drinking water (consumed in the last 6 months), urine, hair, and nails is of immense value. Newer biomarkers of arsenic exposure are being explored to provide early information about arsenic intoxication, of which urinary porphyrin level, blood metallothionein have shown promising results. Controlling the problem of arsenicosis depends on various factors, of which the most important is cessation of intake of arsenic-contaminated water. Deep wells, traditional dug wells, treatment of surface water, rainwater harvesting, and removing arsenic from the contaminated water by arsenic removal plant or arsenic treatment unit are the available options for providing arsenic-free drinking water. The role of nutrition and antioxidants in preventing the onset of symptoms of arsenicosis is also of importance. Nonspecific therapies (e.g., keratolytics for hyperkeratosis) cannot also be ignored and serve as palliative measures. The persons affected need to be followed up at regular intervals to detect the onset of cancers (if any) at the earliest. Role of counseling and education should never be underestimated since absence of public awareness can undermine all efforts of mitigation measures. PMID:19171979

  4. Diagnosis of Food Allergy.

    PubMed

    Chinthrajah, Rebecca Sharon; Tupa, Dana; Prince, Benjamin T; Block, Whitney Morgan; Rosa, Jaime Sou; Singh, Anne Marie; Nadeau, Kari

    2015-12-01

    The prevalence of food allergies has been on the increase over the last 2 decades. Diagnosing food allergies can be complicated, as there are multiple types that have distinct clinical and immunologic features. Food allergies are broadly classified into immunoglobulin E (IgE)-mediated, non-IgE-mediated, or mixed food allergic reactions. This review focuses on the clinical manifestations of the different categories of food allergies and the different tests available to guide the clinician toward an accurate diagnosis. PMID:26456439

  5. Case for diagnosis*

    PubMed Central

    Oliveira, Lorena Cassia de Carvalho; Miranda, Amanda Rodrigues; Pinto, Sebastião Alves; Ianhez, Mayra

    2014-01-01

    A 6 year-old patient began to experience localized hairloss in the right temporal region three years ago. During the first appointment, diagnoses of alopecia areata and congenital triangular alopecia were made. After one year, there was no change. Upon dermatological examination, non-scarring alopecia was noted in the right temporal region, revealing extremely fine and fair hair follicles. A dermoscopy revealed only thin vellus-type hairs. Congenital triangular alopecia is a condition commonly confused with alopecia areata and is thus underdiagnosed. However, well-established clinical parameters and dermoscopic criteria can be used to distinguish skin diseases that affect hair and define the diagnosis. PMID:24770522

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

    ERIC Educational Resources Information Center

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

    2007-01-01

    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

  7. Genetics of Hearing and Deafness

    PubMed Central

    ANGELI, SIMON; LIN, XI; LIU, XUE ZHONG

    2015-01-01

    This article is a review of the genes and genetic disorders that affect hearing in humans and a few selected mouse models of deafness. Genetics is playing an increasingly critical role in the practice of medicine. This is not only in part to the importance that genetic knowledge has on traditional genetic diseases but also in part to the fact that genetic knowledge provides an understanding of the fundamental biological process of most diseases. The proteins coded by the genes related to hearing loss (HL) are involved in many functions in the ear, such as cochlear fluid homeostasis, ionic channels, stereocilia morphology and function, synaptic transmission, gene regulation, and others. Mouse models play a crucial role in understanding of the pathogenesis associated with these genes. Different types of familial HL have been recognized for years; however, in the last two decades, there has been tremendous progress in the discovery of gene mutations that cause deafness. Most of the cases of genetic deafness recognized today are monogenic disorders that can be broadly classified by the mode of inheritance (i.e., autosomal dominant, autosomal recessive, X-linked, and mitochondrial inheritance) and by the presence of associated phenotypic features (i.e., syndromic; and nonsyndromic). In terms of nonsyndromic HL, the chromosomal locations are currently known for ~ 125 loci (54 for dominant and 71 for recessive deafness), 64 genes have been identified (24 for dominant and 40 for recessive deafness), and there are many more loci for syndromic deafness and X-linked and mitochondrial DNA disorders (http://hereditaryhearingloss.org). Thus, today’s clinician must understand the science of medical genetics as this knowledge can lead to more effective disease diagnosis, counseling, treatment, and prevention. PMID:23044516

  8. Genetics of SCID

    PubMed Central

    2010-01-01

    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

  9. Bayesian sequential change diagnosis

    E-print Network

    Dayanik, Savas; Poor, H Vincent

    2007-01-01

    Sequential change diagnosis is the joint problem of detection and identification of a sudden and unobservable change in the distribution of a random sequence. In this problem, the common probability law of a sequence of i.i.d. random variables suddenly changes at some disorder time to one of finitely many alternatives. This disorder time marks the start of a new regime, whose fingerprint is the new law of observations. Both the disorder time and the identity of the new regime are unknown and unobservable. The objective is to detect the regime-change as soon as possible, and, at the same time, to determine its identity as accurately as possible. Prompt and correct diagnosis is crucial for quick execution of the most appropriate measures in response to the new regime, as in fault detection and isolation in industrial processes, and target detection and identification in national defense. The problem is formulated in a Bayesian framework. An optimal sequential decision strategy is found, and an accurate numerica...

  10. Breast cancer early diagnosis based on hybrid strategy.

    PubMed

    Li, Peng; Bi, Tingting; Huang, Jiuling; Li, Siben

    2014-01-01

    The frequent occurrence of breast cancer and its serious consequences have attracted worldwide attention in recent years. Problems such as low rate of accuracy and poor self-adaptability still exist in traditional diagnosis. In order to solve these problems, an AdaBoost-SVM classification algorithm, combined with the cluster boundary sampling preprocessing techniques (CBS-AdaBoost-SVM), is proposed in this paper for the early diagnosis of breast cancer. The algorithm uses machine learning method to diagnose the unknown image data. Moreover, not all of the characteristics play positive roles for classification. To address this issue the paper delete redundant features by using Rough set attribute reduction algorithm based on the genetic algorithm (GA). The effectiveness of the proposed methods are examined on DDSM by calculating its accuracy, confusion matrix, and receiver operating characteristic curves, which give important clues to the physicians for early diagnosis of breast cancer. PMID:25227050

  11. RNA genetics

    SciTech Connect

    Domingo, E. ); Holland, J.J. . Dept. of Biology); Ahlquist, P. . Dept. of Plant Pathology)

    1988-01-01

    This book contains the proceedings on RNA genetics: RNA-directed virus replication Volume 1. Topics covered include: Replication of the poliovirus genome; Influenza viral RNA transcription and replication; and Relication of the reoviridal: Information derived from gene cloning and expression.

  12. Genetic Recombination

    ERIC Educational Resources Information Center

    Whitehouse, H. L. K.

    1973-01-01

    Discusses the mechanisms of genetic recombination with particular emphasis on the study of the fungus Sordaria brevicollis. The study of recombination is facilitated by the use of mutants of this fungus in which the color of the ascospores is affected. (JR)

  13. Upcoming biomarkers for the diagnosis of Kawasaki disease: A review.

    PubMed

    Parthasarathy, Pavithra; Agarwal, Arnav; Chawla, Karan; Tofighi, Taraneh; Mondal, Tapas K

    2015-11-01

    Kawasaki disease (KD) is a major cause of acquired heart disease among children and increases the risk of myocardial infarction. While the biochemical basis of the disease is unclear, the evidence suggests interplay between a microbial infection and a genetic predisposition in the development of the disease. Diagnosis of KD based on clinical observation is not completely reliable and is problematic due to the time-sensitive nature of the disease. Hence, identification of inflammatory, proteomic, and genetic biomarkers may assist in earlier and more effective diagnosis and treatment. This review of observational studies and clinical trials analyzes biomarkers in recent research that may be used to establish a gold standard test for KD diagnosis. 65 articles in the literature are assessed to investigate these new biomarkers in addition to biomarkers presently in use. ESR?40mm/h, leukocyte count ?16?10(9)/L and increased WBC count are together suggestive of the presence of KD. Among proteomic biomarkers, elevated NT-proBNP and differing levels of several other proteomic biomarkers such as iNOS in monocytes and neutrophils have been observed in KD patients. Genetic polymorphisms of six HLA class I genes have also been linked with the disease, alongside MICA alleles A4 and A5.1. The results suggest that NT-proBNP is currently a very promising biomarker for future investigation; further research is warranted to allow for accurate and early detection of the disease using this biomarker. PMID:25749557

  14. Cancer Genetics Professionals

    Cancer.gov

    The information below is from the NCI Cancer Genetics Services Directory.  This directory lists professionals who provide services related to cancer genetics (cancer risk assessment, genetic counseling, genetic susceptibility testing, and others). Professionals

  15. Melanoma genetics.

    PubMed

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2016-01-01

    Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of heritable melanoma risk genes is an important component of disease occurrence. Susceptibility for some families is due to mutation in one of the known high penetrance melanoma predisposition genes: CDKN2A, CDK4, BAP1, POT1, ACD, TERF2IP and TERT. However, despite such mutations being implicated in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed in melanoma families at rates greater than expected by chance. The most extensively documented association is between CDKN2A germ line mutations and pancreatic cancer, and a cancer syndrome including cutaneous melanoma, uveal melanoma and mesothelioma has been proposed for BAP1 germ line mutations. Other medium to high penetrance melanoma predisposition genes have been associated with renal cell carcinoma (MITF, BAP1) and glioma (POT1). These associations between melanoma and other cancers hint at the possibility of common pathways for oncogenesis, and better knowledge of these pathways may improve understanding of the genetic basis underpinning familial melanoma. It is likely that 'melanoma' risk genes will impact on mutation screening and genetic counselling not only for melanoma but also a range of other cancers. PMID:26337759

  16. Enteropathic Spondyloarthritis: From Diagnosis to Treatment

    PubMed Central

    Peluso, Rosario; Di Minno, Matteo Nicola Dario; Iervolino, Salvatore; Manguso, Francesco; Tramontano, Giuseppina; Ambrosino, Pasquale; Esposito, Carmela; Scalera, Antonella; Castiglione, Fabiana; Scarpa, Raffaele

    2013-01-01

    Enteropathic arthritis (EA) is a spondyloarthritis (SpA) which occurs in patients with inflammatory bowel diseases (IBDs) and other gastrointestinal diseases. Diagnosis is generally established on the medical history and physical examination. It was, generally, made according to the European Spondyloarthropathy Study Group (ESSG) criteria. Rheumatic manifestations are the most frequent extraintestinal findings of IBD with a prevalence between 17% and 39%, and IBD is associated, less frequently, with other rheumatic disease such as rheumatoid arthritis, Sjogren syndrome, Takayasu arteritis, and fibromyalgia. Although the pathogenesis of EA has not been plainly clarified, the most popular theory supposes that joint inflammation occurs in genetically predisposed subjects with bacterial gut infections, provided an important evidence for a possible relationship between inflammation of the gut mucosa and arthritis. The management of patients with EA requires an active cooperation between the gastroenterologist and rheumatologist. PMID:23690825

  17. Pancreatic neuroendocrine tumors: biology, diagnosis, and treatment

    PubMed Central

    Ro, Cynthia; Chai, Wanxing; Yu, Victoria E.; Yu, Run

    2013-01-01

    Pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in the pancreas, are among the most common neuroendocrine tumors. The genetic causes of familial and sporadic PNETs are somewhat understood, but their molecular pathogenesis remains unknown. Most PNETs are indolent but have malignant potential. The biological behavior of an individual PNET is unpredictable; higher tumor grade, lymph node and liver metastasis, and larger tumor size generally indicate a less favorable prognosis. Endocrine testing, imaging, and histological evidence are necessary to accurately diagnose PNETs. A 4-pronged aggressive treatment approach consisting of surgery, locoregional therapy, systemic therapy, and complication control has become popular in academic centers around the world. The optimal application of the multiple systemic therapeutic modalities is under development; efficacy, safety, availability, and cost should be considered when treating a specific patient. The clinical presentation, diagnosis, and treatment of specific types of PNETs and familial PNET syndromes, including the novel Mahvash disease, are summarized. PMID:23237225

  18. Diagnosis and Treatment of Fetal Arrhythmia

    PubMed Central

    Wacker-Gussmann, Annette; Strasburger, Janette F.; Cuneo, Bettina F.; Wakai, Ronald T.

    2014-01-01

    Detection and careful stratification of fetal heart rate (FHR) is extremely important in all pregnancies. The most lethal cardiac rhythm disturbances occur during apparently normal pregnancies where FHR and rhythmare regular and within normal or low-normal ranges. These hidden depolarization and repolarization abnormalities, associated with genetic ion channelopathies cannot be detected by echocardiography, and may be responsible for up to 10% of unexplained fetal demise, prompting a need for newer and better fetal diagnostic techniques. Other manifest fetal arrhythmias such as premature beats, tachycardia, and bradycardia are commonly recognized. Heart rhythm diagnosis in obstetrical practice is usually made by M-mode and pulsed Doppler fetal echocardiography, but not all fetal cardiac time intervals are captured by echocardiographic methods. This article reviews different types of fetal arrhythmias, their presentation and treatment strategies, and gives an overview of the present and future diagnostic techniques. PMID:24858320

  19. Determining the Pathogenicity of Genetic Variants Associated with Cardiac Channelopathies

    PubMed Central

    Campuzano, Oscar; Allegue, Catarina; Fernandez, Anna; Iglesias, Anna; Brugada, Ramon

    2015-01-01

    Advancements in genetic screening have generated massive amounts of data on genetic variation; however, a lack of clear pathogenic stratification has left most variants classified as being of unknown significance. This is a critical limitation for translating genetic data into clinical practice. Genetic screening is currently recommended in the guidelines for diagnosis and treatment of cardiac channelopathies, which are major contributors to sudden cardiac death in young people. We propose to characterize the pathogenicity of genetic variants associated with cardiac channelopathies using a stratified scoring system. The development of this system was considered by using all of the tools currently available to define pathogenicity. The use of this scoring system could help clinicians to understand the limitations of genetic associations with a disease, and help them better define the role that genetics can have in their clinical routine. PMID:25608792

  20. Hybrid Systems Diagnosis

    NASA Technical Reports Server (NTRS)

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

    2005-01-01

    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.

  1. [Differential diagnosis of synovitis].

    PubMed

    Morawietz, L; Fernahl, G; Krenn, V

    2008-11-01

    The synovial membrane is a site where many diseases with different etiologies can become manifest. Tumors and storage diseases are some of the rare conditions, whereas crystal deposition diseases, acute bacterial infections and in particular chronic uncharacteristic synovitis are frequently encountered. The latter present a diagnostic problem, because they can barely be assigned to concrete diagnoses. This report will give an overview of the differential diagnosis of joint diseases and will focus on the so-called synovitis score as a tool for the systematic evaluation of chronic uncharacteristic synovitis, providing a possibility to differentiate between degenerative and rheumatic synovitis with a specificity of 60.5% and a sensitivity of 95.5%. PMID:18709370

  2. Genetics of adolescent idiopathic scoliosis.

    PubMed Central

    Czeizel, A; Bellyei, A; Barta, O; Magda, T; Molnár, L

    1978-01-01

    A genetic family study was undertaken by photofluorography of the first, second, and third degree relatives of 116 index patients with adolescent idiopathic scoliosis (AIS). The index patients were ascertained in the course of an epidemiological screening. The pattern of familial clusters and the recurrence risk related to the number of affected relatives and to the severity of the disorder in the index patients support the theory of polygenic inheritance, a multifactorial-threshold aetiological model. The recurrence risk table for first degree relative, prepared by computerised data processing and analysis, may contribute to the early diagnosis and prevention of the disorder. PMID:745214

  3. [Salmonella diagnosis and expanded bacteriologic differential diagnosis using Rambach agar].

    PubMed

    Wermter, R; Müller, U

    1995-05-01

    The present study gives not only additional advises and ideas for the use of Rambach agar but also diagnostic support. Resulting from several years of diagnostic experience the medium can be recommended for enlarged routine differential-diagnosis of bacteria and also for improved Salmonella-diagnosis as an alternative medium (under section 35 LMBG; Untersuchung von Lebensmitteln; Nachweis von Salmonellen). PMID:7575387

  4. Genetic background of supernumerary teeth

    PubMed Central

    Subasioglu, Asli; Savas, Selcuk; Kucukyilmaz, Ebru; Kesim, Servet; Yagci, Ahmet; Dundar, Munis

    2015-01-01

    Supernumerary teeth (ST) are odontostomatologic anomaly characterized by as the existence excessive number of teeth in relation to the normal dental formula. This condition is commonly seen with several congenital genetic disorders such as Gardner's syndrome, cleidocranial dysostosis and cleft lip and palate. Less common syndromes that are associated with ST are; Fabry Disease, Ellis-van Creveld syndrome, Nance-Horan syndrome, Rubinstein-Taybi Syndrome and Trico–Rhino–Phalangeal syndrome. ST can be an important component of a distinctive disorder and an important clue for early diagnosis. Certainly early detecting the abnormalities gives us to make correct management of the patient and also it is important for making well-informed decisions about long-term medical care and treatment. In this review, the genetic syndromes that are related with ST were discussed. PMID:25713500

  5. Genetics Home Reference: Achondroplasia

    MedlinePLUS

    ... Where can I find information about diagnosis or management of achondroplasia? These resources address the diagnosis or management of achondroplasia and may include treatment providers. GeneFacts: ...

  6. Religious Traditions and Prenatal Genetic Counseling

    PubMed Central

    Anderson, Rebecca Rae

    2009-01-01

    Members of organized religious groups may look to their faith traditions for guidance regarding the moral implications of prenatal diagnosis and intervention. Many denominations have doctrinal statements relevant to these deliberations. In this paper, common spiritual issues arising in the genetic counseling encounter are described. Representative doctrinal positions, derived from the responses of 31 U.S. religious denominations to a survey relating to prenatal genetic counseling, are given. Because the long-term adjustment of patients may be dependent in part on their ability to reconcile their actions with their faith traditions, genetic counselors best serve their patients when they invite discussion of matters of faith. Unless invited, patients may assume these topics are ‘off limits’ or that care providers are indifferent to their beliefs. Although genetics professionals ought not assume the role of spiritual advisor, a working knowledge of doctrinal approaches should help counselors frame the issues, and avoid missteps. PMID:19170093

  7. Epileptic syndromes: From clinic to genetic

    PubMed Central

    Tafakhori, Abbas; Aghamollaii, Vajiheh; Faghihi-Kashani, Sara; Sarraf, Payam; Habibi, Laleh

    2015-01-01

    Epilepsy is one of the most common neurological disorders. Studies have demonstrated that genetic factors have a strong role in etiology of epilepsy. Mutations in genes encoding ion channels, neurotransmitters and other proteins involved in the neuronal biology have been recognized in different types of this disease. Moreover, some chromosomal aberration including ring chromosomes will result in epilepsy. In this review, we intend to highlight the role of molecular genetic in etiology of epilepsy syndromes, inspect the most recent classification of International League against Epilepsy and discuss the role of genetic counseling and genetic testing in management of epilepsy syndromes. Furthermore, we emphasize on collaboration of neurologists and geneticists to improve diagnosis and management. PMID:25874049

  8. Genetics of inherited primary arrhythmia disorders

    PubMed Central

    Spears, Danna A; Gollob, Michael H

    2015-01-01

    A sudden unexplained death is felt to be due to a primary arrhythmic disorder when no structural heart disease is found on autopsy, and there is no preceding documentation of heart disease. In these cases, death is presumed to be secondary to a lethal and potentially heritable abnormality of cardiac ion channel function. These channelopathies include congenital long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, and short QT syndrome. In certain cases, genetic testing may have an important role in supporting a diagnosis of a primary arrhythmia disorder, and can also provide prognostic information, but by far the greatest strength of genetic testing lies in the screening of family members, who may be at risk. The purpose of this review is to describe the basic genetic and molecular pathophysiology of the primary inherited arrhythmia disorders, and to outline a rational approach to genetic testing, management, and family screening. PMID:26425105

  9. Clinical review of genetic epileptic encephalopathies

    PubMed Central

    Noh, Grace J.; Asher, Y. Jane Tavyev; Graham, John M.

    2012-01-01

    Seizures are a frequently encountered finding in patients seen for clinical genetics evaluations. The differential diagnosis for the cause of seizures is quite diverse and complex, and more than half of all epilepsies have been attributed to a genetic cause. Given the complexity of such evaluations, we highlight the more common causes of genetic epileptic encephalopathies and emphasize the usefulness of recent technological advances. The purpose of this review is to serve as a practical guide for clinical geneticists in the evaluation and counseling of patients with genetic epileptic encephalopathies. Common syndromes will be discussed, in addition to specific seizure phenotypes, many of which are refractory to anti-epileptic agents. Divided by etiology, we overview the more common causes of infantile epileptic encephalopathies, channelopathies, syndromic, metabolic, and chromosomal entities. For each condition, we will outline the diagnostic evaluation and discuss effective treatment strategies that should be considered. PMID:22342633

  10. Modeling the Diagnostic Criteria for Alcohol Dependence with Genetic Animal Models

    PubMed Central

    Kendler, Kenneth S.; Hitzemann, Robert J.

    2012-01-01

    A diagnosis of alcohol dependence (AD) using the DSM-IV-R is categorical, based on an individual’s manifestation of three or more symptoms from a list of seven. AD risk can be traced to both genetic and environmental sources. Most genetic studies of AD risk implicitly assume that an AD diagnosis represents a single underlying genetic factor. We recently found that the criteria for an AD diagnosis represent three somewhat distinct genetic paths to individual risk. Specifically, heavy use and tolerance versus withdrawal and continued use despite problems reflected separate genetic factors. However, some data suggest that genetic risk for AD is adequately described with a single underlying genetic risk factor. Rodent animal models for alcohol-related phenotypes typically target discrete aspects of the complex human AD diagnosis. Here, we review the literature derived from genetic animal models in an attempt to determine whether they support a single-factor or multiple-factor genetic structure. We conclude that there is modest support in the animal literature that alcohol tolerance and withdrawal reflect distinct genetic risk factors, in agreement with our human data. We suggest areas where more research could clarify this attempt to align the rodent and human data. PMID:21910077

  11. Array-based approaches in prenatal diagnosis.

    PubMed

    Brady, Paul D; Devriendt, Koenraad; Deprest, Jan; Vermeesch, Joris R

    2012-01-01

    The diagnostic benefits of array comparative genomic hybridisation (CGH) have been demonstrated, with this technique now being applied as the first-line test for patients with intellectual disabilities and/or multiple congenital anomalies in numerous laboratories. There are no technical barriers preventing the introduction of array CGH to prenatal diagnosis. The question is rather how this is best implemented, and for whom. The challenges lie in the interpretation of copy number variations, particularly those which exhibit reduced penetrance or variable expression, and how to deal with incidental findings, which are not related to the observed foetal anomalies, or unclassified variants which are currently of uncertain clinical significance. Recently, applications of array technologies to the field of pre-implantation genetic diagnosis have also been demonstrated. It is important to address the ethical questions raised concerning the genome-wide analysis of prenatal samples to ensure the maximum benefit for patients. We provide an overview of the recent developments on the use of array CGH in the prenatal setting, and address the challenges posed. PMID:22228011

  12. Celiac disease: Prevalence, diagnosis, pathogenesis and treatment

    PubMed Central

    Gujral, Naiyana; Freeman, Hugh J; Thomson, Alan BR

    2012-01-01

    Celiac disease (CD) is one of the most common diseases, resulting from both environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non-HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world. However, the population with diabetes, autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD, at least in part, because of shared HLA typing. Gliadin gains access to the basal surface of the epithelium, and interact directly with the immune system, via both trans- and para-cellular routes. From a diagnostic perspective, symptoms may be viewed as either “typical” or “atypical”. In both positive serological screening results suggestive of CD, should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase antibody or anti-endomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy. Currently, the only treatment available for CD individuals is a strict life-long GFD. A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective deamidation of specific glutamine residues by tissue, restore immune tolerance towards gluten, modulation of immune response to dietary gliadin, and restoration of intestinal architecture. PMID:23155333

  13. Human genetics

    SciTech Connect

    Carlson, E.A.

    1984-01-01

    This text provides full and balanced coverage of the concepts requisite for a thorough understanding of human genetics. Applications to both the individual and society are integrated throughout the lively and personal narrative, and the essential principles of heredity are clearly presented to prepare students for informed participation in public controversies. High-interest, controversial topics, including recombinant DNA technology, oncogenes, embryo transfer, environmental mutagens and carcinogens, IQ testing, and eugenics encourage understanding of important social issues.

  14. Epilepsy genetics: the ongoing revolution.

    PubMed

    Lesca, G; Depienne, C

    2015-01-01

    Epilepsies have long remained refractory to gene identification due to several obstacles, including a highly variable inter- and intrafamilial expressivity of the phenotypes, a high frequency of phenocopies, and a huge genetic heterogeneity. Recent technological breakthroughs, such as array comparative genomic hybridization and next generation sequencing, have been leading, in the past few years, to the identification of an increasing number of genomic regions and genes in which mutations or copy-number variations cause various epileptic disorders, revealing an enormous diversity of pathophysiological mechanisms. The field that has undergone the most striking revolution is that of epileptic encephalopathies, for which most of causing genes have been discovered since the year 2012. Some examples are the continuous spike-and-waves during slow-wave sleep and Landau-Kleffner syndromes for which the recent discovery of the role of GRIN2A mutations has finally confirmed the genetic bases. These new technologies begin to be used for diagnostic applications, and the main challenge now resides in the interpretation of the huge mass of variants detected by these methods. The identification of causative mutations in epilepsies provides definitive confirmation of the clinical diagnosis, allows accurate genetic counselling, and sometimes permits the development of new appropriate and specific antiepileptic therapies. Future challenges include the identification of the genetic or environmental factors that modify the epileptic phenotypes caused by mutations in a given gene and the understanding of the role of somatic mutations in sporadic epilepsies. PMID:26003806

  15. Current Controversies in Diagnosis and Management of Cleft Palate and Velopharyngeal Insufficiency

    PubMed Central

    Ysunza, Pablo Antonio; Repetto, Gabriela M.; Pamplona, Maria Carmen; Calderon, Juan F.; Shaheen, Kenneth; Chaiyasate, Konkgrit; Rontal, Matthew

    2015-01-01

    Background. One of the most controversial topics concerning cleft palate is the diagnosis and treatment of velopharyngeal insufficiency (VPI). Objective. This paper reviews current genetic aspects of cleft palate, imaging diagnosis of VPI, the planning of operations for restoring velopharyngeal function during speech, and strategies for speech pathology treatment of articulation disorders in patients with cleft palate. Materials and Methods. An updated review of the scientific literature concerning genetic aspects of cleft palate was carried out. Current strategies for assessing and treating articulation disorders associated with cleft palate were analyzed. Imaging procedures for assessing velopharyngeal closure during speech were reviewed, including a recent method for performing intraoperative videonasopharyngoscopy. Results. Conclusions from the analysis of genetic aspects of syndromic and nonsyndromic cleft palate and their use in its diagnosis and management are presented. Strategies for classifying and treating articulation disorders in patients with cleft palate are presented. Preliminary results of the use of multiplanar videofluoroscopy as an outpatient procedure and intraoperative endoscopy for the planning of operations which aimed to correct VPI are presented. Conclusion. This paper presents current aspects of the diagnosis and management of patients with cleft palate and VPI including 3 main aspects: genetics and genomics, speech pathology and imaging diagnosis, and surgical management. PMID:26273595

  16. GENETICS | REVIEW Genetic Diversity and Societally

    E-print Network

    Rosenberg, Noah

    GENETICS | REVIEW Genetic Diversity and Societally Important Disparities Noah A. Rosenberg1 The magnitude of genetic diversity within human populations varies in a way that reflects the sequence of migrations by which people spread throughout the world. Beyond its use in human evolutionary genetics

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

    SciTech Connect

    Aaltonen, J.; Bjoerses, P.; Peltonen, L.

    1994-09-01

    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.

  18. Primary pulmonary synovial sarcoma: Diagnosis on squash smears.

    PubMed

    Yaseen, Syed Besina; Mustafa, Farhat; Rafiq, Danish; Makhdoomi, Rumana; Chanda, Nassima

    2015-01-01

    Synovial sarcomas are rare tumors accounting for approximately 5-10% of soft tissue sarcomas. They occur predominantly in the extremities, followed by head and neck. Primary pulmonary sarcomas are very rare and comprise only 0.5% of all primary lung malignancies. The diagnosis is established only after sarcomas like primary lung malignancies, and metastatic sarcomas have been excluded. For synovial sarcomas that arise at unusual locations, a definitive diagnosis is challenging and requires the use of ancillary diagnostic procedures such as immunohistochemistry (IHC) and molecular genetic techniques for confirmation of diagnosis. We report a case of 29-year-old male who had right lower lobe lung mass. He underwent right lower lobectomy. Intraoperative squash smears revealed spindle cell sarcoma. Subsequent histopathology and IHC confirmed the diagnosis as synovial sarcoma. We report this case on account of its rarity and to emphasize the utility of intraoperative squash smears in the diagnosis of such cases, which has been under-utilized in clinical practice. PMID:25948950

  19. From prenatal genomic diagnosis to fetal personalized medicine: progress and challenges

    PubMed Central

    Bianchi, Diana W

    2015-01-01

    Thus far, the focus of personalized medicine has been the prevention and treatment of conditions that affect adults. Although advances in genetic technology have been applied more frequently to prenatal diagnosis than to fetal treatment, genetic and genomic information is beginning to influence pregnancy management. Recent developments in sequencing the fetal genome combined with progress in understanding fetal physiology using gene expression arrays indicate that we could have the technical capabilities to apply an individualized medicine approach to the fetus. Here I review recent advances in prenatal genetic diagnostics, the challenges associated with these new technologies and how the information derived from them can be used to advance fetal care. Historically, the goal of prenatal diagnosis has been to provide an informed choice to prospective parents. We are now at a point where that goal can and should be expanded to incorporate genetic, genomic and transcriptomic data to develop new approaches to fetal treatment. PMID:22772565

  20. Etiological diagnosis of hyperprolactinemia.

    PubMed

    Cortet-Rudelli, C; Sapin, R; Bonneville, J-F; Brue, T

    2007-06-01

    There are numerous etiologies of hyperprolactinemia, a common reason for consultation. Diagnostic measures must be capable of identifying the tumors, the most frequent of which are prolactin adenomas. Hypothalamic-pituitary MRI is the reference morphological examination. In clinical practice, it is usually performed very early, following the discovery of increased plasma concentrations of PRL. This approach is warranted for marked increase in PRL in the absence of drugs with hyperprolactinemic effects (>10 x upper limit of normal) since a diagnosis of PRL adenoma is extremely likely under such circumstances. When hyperprolactinemia is moderate, which is the most common finding in practice, all etiologies are possible in theory and it is important to follow a rational diagnostic plan (history-taking to identify use of any drugs with hyperprolactinemic effects paying attention to renal and hepatic history, investigation for endocrine diseases occasionally associated with hyperprolactinemia such as hypothyroidism or polycystic ovary syndrome (PCOS), confirmation of hyperprolactinemia by a second assay when the initial level is less than five times the upper normal limit, pregnancy testing for women of childbearing age) in order to rule out all non-tumoral causes of hyperprolactinemia before proceeding with imaging. Absence of any consequences of hyperprolactinemia on gonadic function or the existence of a concomitant disease that could account for the clinical signs, demonstration of wide variations in PRL from one assay to another in a single patient could prompt screening for macroprolactinemia before MRI is ordered. Macroprolactinoma could also occur in the case of normal or doubtful MRI or discrepancy in response to medical or surgical treatment. T1- and T2-weighted coronal sections (with or without T1 after gadolinium injection) are generally sufficient for diagnosis of microprolactinoma. Dynamic tests may be useful if MRI is normal or unclear. Gadolinium injection with sagittal and axial sections is essential for examination of large lesions. In this case, when the increase of PRL is moderate (<150 mg/ml), a non-lactotropic lesion may be suspected without misdiagnosing a hook effect. Careful analysis of the images allows differentiation between tumoral lesions and pituitary hyperplasia. PMID:17524347

  1. Current Diagnosis and Treatment of Anxiety Disorders

    PubMed Central

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

    2013-01-01

    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

  2. Auto inflammatory syndromes: Diagnosis and treatment.

    PubMed

    Stankovic, Katia; Grateau, Gilles

    2007-12-01

    Hereditary recurrent fevers are rare genetic diseases characterized by apparently spontaneous attacks of inflammation. They include familial Mediterranean fever (FMF); tumor necrosis factor (TNF) receptor periodic syndrome (TRAPS); hyperimmunoglobulinemia D syndrome (HIDS); and hereditary periodic fevers related to mutations in the CIAS1 (cold induced autoinflammatory syndrome 1) gene, such as Muckle-Wells syndrome, familial cold urticaria, and CINCA/NOMID (chronic infantile neurological cutaneous and articular/neonatal-onset multisystemic inflammatory disease). Musculoskeletal manifestations are common. They may occur as features of the acute inflammatory attacks or persist for longer periods. Among them, the most common include arthritis of the large and medium-sized joints in FMF and CINCA, arthralgia in HIDS, and myalgia or pseudo-fasciitis in TRAPS. The outcome is usually favorable, although joint destruction may develop in CINCA or at the hip in FMF. The recurrent bouts of fever and accompanying clinical manifestations suggest the diagnosis, which can be confirmed by genetic testing. Among differential diagnoses, infection should be considered routinely. The treatment of the inflammatory attacks is nonspecific. New pathophysiological insights have led to the development of promising maintenance treatments designed to reduce the number and severity of the inflammatory attacks and to diminish the risk of secondary amyloidosis. PMID:17950649

  3. How genetics came to the unborn: 1960-2000.

    PubMed

    Löwy, Ilana

    2014-09-01

    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

  4. Bronchoscopic diagnosis of pneumonia.

    PubMed Central

    Baselski, V S; Wunderink, R G

    1994-01-01

    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

  5. [Mantle cell lymphoma diagnosis].

    PubMed

    Choukri, Mohammed; Taheri, Hafsa; Seddik, Rachid; Benkirane, Souad; Hamama, Afaf; Masrar, Azzelarab; Agoumi, Najia Benkirane; Chabraoui, Layachi

    2013-01-01

    Recent classifications of non-Hodgkin's lymphomas based on combination of morphologic, immunophenotypic, and cytogenetic criteria have individualized mantle cell lymphoma (MCL). This clinico-biological entity which accounts for 3 to 10% of all non-Hodgkin's lymphomas, now appears to be a biological and therapeutic model for the understanding and treatment of hematologic malignancies. The present study consisting of two cases of MCL collated at laboratory of hematology of Rabat Ibn Sina hospital. The morphological appearance of MCL is characterized by diffuse or nodular lymph infiltration in the mantle zone, the osteo-medullary biopsy shows an interstitial infringement characterized by the presence of lymphocytes resembling centrocytes with cleaved and angular nuclei, dispersed chromatin, inconspicuous nucleoli and scanty cytoplasm. The flow cytometry showed immunophenotype positive for surface Ig, CD19, CD20, CD22, CD79b, CD5 and cyclin D1, and negative for CD10, CD23 and CD25. In conclusion, the methods of diagnosis and prognosis evaluation of mantle cell lymphoma are based on the nodular, medullary and blood morphology, the immunophenotypic, cytogenetic and molecular study of neoplastic cells. PMID:23396434

  6. Pitfalls in developmental diagnosis.

    PubMed

    Blasco, P A

    1991-12-01

    The more common and more glaring pitfalls in developmental diagnosis encountered during infancy and early childhood have been outlined. Much of the ability to avoid these traps depends on a comfortable understanding of the four spheres of early child development and a sound familiarity with the principles of developmental assessment, especially the separation of intellectual and motor entities. Motor milestones are excellent indicators of motor competence but correlate poorly with intellectual capacity. Language and problem-solving milestones in infancy provide the best insights into a child's intellectual potential, and their evolution is independent of motor competence. They may be obscured by motor disability and as a result may be more difficult to demonstrate, but that is a separate issue. In that instance there is nothing subtle about the fact that one is already dealing with a disabled infant. Psychosocial abilities (affective milestones) are critical in understanding the whole child and in making a meaningful statement about behavior, but they lend little additional information to the assessment of intellectual and motor competence. For physicians the "curb-side consult" is a highly efficient tool that has great practical application to developmental concerns and especially to the avoidance of the pitfalls described. Every practitioner should have a resource in developmental and behavioral pediatrics with whom he or she can communicate in an informal fashion. This is especially valuable in situations in which the urgency or even the need for referral (a time-consuming, expensive, and often anxiety-provoking process) is not clear. PMID:1719470

  7. Avian toxicologic diagnosis

    USGS Publications Warehouse

    Sigurdson, C.J.; Franson, J.C.

    2000-01-01

    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.

  8. [Diagnosis of extrauterine pregnancy].

    PubMed

    Giambanco, V; Giambanco, L; Alaimo, D

    1999-01-01

    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

  9. Molecular Biology, Pathobiology, and Genetics Intrinsic Gene Expression Profiles of Gliomas Are a Better

    E-print Network

    Molecular Biology, Pathobiology, and Genetics Intrinsic Gene Expression Profiles of Gliomas value of molecular subgroups was validated on five independent sample cohorts (The Cancer Genome Atlas. Molecular classification therefore may aid diagnosis and can guide clinical decision making. [Cancer Res

  10. Integrative analysis of heterogeneous genomic datasets to discover genetic etiology of autism spectrum disorders

    E-print Network

    Nazeen, Sumaiya

    2014-01-01

    Understanding the genetic background of complex diseases is crucial to medical research, with implications to diagnosis, treatment and drug development. As molecular approaches to this challenge are time consuming and ...

  11. Video-assisted laparoscopy for the detection and diagnosis of endometriosis: safety, reliability, and invasiveness

    PubMed Central

    Schipper, Erica; Nezhat, Camran

    2012-01-01

    Endometriosis is a highly enigmatic disease with multiple presentations ranging from infertility to severe pain, often causing significant morbidity. Video-assisted laparoscopy (VALS) has now replaced laparotomy as the gold standard for the diagnosis and management of endometriosis. While imaging has a role in the evaluation of some patients, histologic examination is needed for a definitive diagnosis. Laboratory evaluation currently has a minor role in the diagnosis of endometriosis, although studies are underway investigating serum markers, genetic studies, and endometrial sampling. A high index of suspicion is essential to accurately diagnose this complex condition, and a multidisciplinary approach is often indicated. The following review discusses laparoscopic diagnosis of endometriosis from the pre-operative evaluation of patients suspected of having endometriosis to surgical technique for safe and adequate laparoscopic diagnosis of the condition and postsurgical care. PMID:22927769

  12. Pheochromocytomas and Paragangliomas: Clinical and Genetic Approaches

    PubMed Central

    Costa, Marcia Helena Soares; Ortiga-Carvalho, Tania M.; Violante, Alice Dutra; Vaisman, Mario

    2015-01-01

    Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors derived from the chromaffin tissue. Diagnosis of these tumors is extremely important as they are linked to the hypertension syndrome with great cardiovascular morbidity and mortality. A great majority of PCCs and PGLs are sporadic and benign tumors; however, the classic idea of 10% exception of these features is changing. The description of new genes linked to familial forms of PCC/PGLs, such as succinate dehydrogenase (SDH) complex subunits, KIF1B?, EGLN1, TMEM127, and MAX, added to the well-known PCC familial syndrome (MEN2, VHL, and neurofibromatosis type 1) presents new challenges for diagnosis. In this review, we discuss the diversity of clinical and genetic approaches to this syndrome as well the diverse criteria that should guide genetic investigation. PMID:26347711

  13. Artificial Intelligence Approaches to Medical Diagnosis

    E-print Network

    Rubin, Andee

    The differential diagnosis of hematuria, blood in the urine, is studied from the point of view of identifying crucial structures and processes in medical diagnosis. The thesis attempts to fit the problem of medical diagnosis ...

  14. Biology 2250 Principles of Genetics

    E-print Network

    Innes, David J.

    in genetics (GMO, gene therapy...) What is Genetics ? - Genetics is the study of heredity and variation American J. Human Genetics Heredity Annals of Human Genetics Hereditas Opthalmic Genetics Japanese Journal of Human Genetics Human Genetics Journal of Heredity Current Genetics Molecular Biology and Evolution

  15. Importance of genetic evaluation and testing in pediatric cardiomyopathy

    PubMed Central

    Tariq, Muhammad; Ware, Stephanie M

    2014-01-01

    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. PMID:25429328

  16. Osteoarthritis: understanding the pathophysiology, genetics, and treatments.

    PubMed Central

    Sinkov, Vladamir; Cymet, Tyler

    2003-01-01

    Risk factors for developing osteoarthritis include age, previous joint injury, obesity, and a genetic predisposition. An imbalance of joint functioning initiates the disease process, which is then worsened through biochemical changes in the collagen in the joint. Joint pain is the cardinal clinical presentation. Radiographic and lab testing do not correlate well with the disease; therefore, diagnosis is made by clinical findings. Treatment focuses on maintaining joint function through the use of directed activity, physical therapy, and medications. PMID:12856913

  17. Molecular genetics in clinical practice: evolution of a DNA diagnostic service.

    PubMed Central

    Meredith, A. L.; Upadhyaya, M.; Harper, P. S.

    1988-01-01

    The development of a molecular genetics diagnostic service over a three year period was studied in a National Health Service region with a population of three million. Starting from a time when few diagnostic applications were possible, the number of disorders and the overall demand had grown rapidly. Conditions for which molecular genetic diagnosis had been provided included Duchenne and Becker muscular dystrophy, myotonic dystrophy, Huntington's disease, and cystic fibrosis. Of 405 requests for diagnosis, 151 (37%) related to determination of carrier state, 187 (46%) to determining the feasibility of future prenatal diagnosis, and 67 (17%) were prenatal diagnostic biopsy samples, almost exclusively of first trimester chorion. DNA samples for future diagnostic use with a wide range of genetic disorders had also been banked. The study showed a need for close integration with clinical genetics services to allow satisfactory genetic counselling and interpretation of risks. PMID:2972330

  18. Contact Dermatitis: Diagnosis, Treatment, and Outcome

    MedlinePLUS

    ... A - D Contact dermatitis Diagnosis, treatment, and outcome Contact dermatitis: Diagnosis, treatment, and outcome How dermatologists diagnose contact dermatitis To diagnose this common skin condition, dermatologists: ...

  19. Prenatal Diagnosis of Antley-Bixler Syndrome and POR Deficiency.

    PubMed

    Oldani, Elena; Garel, Catherine; Bucourt, Martine; Carbillon, Lionel

    2015-01-01

    BACKGROUND Prenatal diagnosis of severe bone diseases is challenging and requires complete and precise analysis of fetal anomalies to guide genetic investigation and parental counselling. CASE REPORT We report a rare case of Antley-Bixler syndrome prenatally diagnosed at 26 weeks' gestation by ultrasound and computed tomography in a 28-year-old woman with a history of early termination of pregnancy for "malposition of the inferior limbs". The prenatal ultrasound scan showed severe femoral bowing and frontal bossing. Taking into account the high probability of a recurrent severe skeletal disorder, a computed tomography (CT) scan was proposed. CT findings revealed bilateral femora deformation, craniosynostosis, severe midface hypoplasia, and radiohumeral synostosis. These anomalies strongly suggested Antley-Bixler syndrome. Sequencing of the POR gene in the fetus and the parents revealed compound heterozygous mutations in exon 9 and intron 7, both inherited from each parent, and this finding allowed genetic counseling. CONCLUSIONS The first step in the proper prenatal diagnosis of fetal bone disorders is the precise analysis of ultrasonographic images. However, when a severe fetal inherited disorder is strongly suspected in late mid-trimester, CT may be discussed and usefully contribute to diagnosis and prognosis assessment. PMID:26670660

  20. Celiac Disease Diagnosis: Endoscopic Biopsy

    MedlinePLUS

    ... Fiction Symptoms Screening Diagnosis Treatment Factsheets ... how celiac disease is diagnosed Only a biopsy lets you know for sure If screening tests and/or symptoms suggest celiac disease, your doctor ...

  1. DCTD — Cancer Diagnosis Program (CDP)

    Cancer.gov

    Skip to Content Click here to view the Site Map Home | Sitemap | Contact DCTD Search this site Cancer Diagnosis Program (CDP) Introduction Major Ongoing Initiatives Current Funding Opportunities Partnerships and Collaborations Scientific Advances Tools,

  2. The role of cloned genes in the prevention of genetic disease.

    PubMed

    Weatherall, D J; Old, J M; Thein, S L; Wainscoat, J S

    1988-06-15

    The application of recombinant DNA technology to the study of human genetic disease promises to increase the scope for carrier detection and prenatal diagnosis. Here we summarize current experience with prenatal diagnosis of single-gene disorders by DNA analysis and highlight some of the technical and organizational problems that remain to be solved. PMID:2900519

  3. Diagnosis of metabolic bone disease

    SciTech Connect

    Grech, P.; Martin, T.J.; Barrington, N.A.; Ell, P.J.

    1986-01-01

    This book presents a reference on the radiologic evaluation, features, and differential diagnosis of metabolic diseases involving the whole skeleton, calcium deficiencies resulting from pharmacologic agents, and bone changes related to endocrine disturbances. It also stresses how radiology, nuclear medicine, and biochemistry - either alone or in concert - contribute to clinical diagnosis. It covers renal bone disease, Paget's disease, hyperphosphatasia, extraskeletal mineralization, metabolic bone disorders related to malnutrition, tumors, plus radionuclide studies including materials and methods.

  4. Specific Genetic Disorders

    MedlinePLUS

    ... links from the National Institutes of Health. Specific Genetic Disorders Many human diseases have a genetic component. ... Condition in an Adult The Undiagnosed Diseases Program Genetic Disorders Achondroplasia Alpha-1 Antitrypsin Deficiency Antiphospholipid Syndrome ...

  5. Genetic Testing (For Parents)

    MedlinePLUS

    ... Kids Deal With Bullies Pregnant? What to Expect Genetic Testing KidsHealth > Parents > Doctors & Hospitals > Medical Tests & Exams > ... blood, skin, bone, or other tissue is needed. Genetic Testing During Pregnancy For genetic testing before birth, ...

  6. Genetic Counseling (For Parents)

    MedlinePLUS

    ... Kids Deal With Bullies Pregnant? What to Expect Genetic Counseling KidsHealth > Parents > Doctors & Hospitals > Medical Tests & Exams > ... how can they help your family? What Is Genetic Counseling? Genetic counseling is the process of: evaluating ...

  7. Genetic Testing for ALS

    MedlinePLUS

    ... Involved Donate Familial Amyotrophic Lateral Sclerosis (FALS) and Genetic Testing By Deborah Hartzfeld, MS, CGC, Certified Genetic ... guarantee a person will develop symptoms of ALS. Genetic Counseling If there is more than one person ...

  8. Biology 4250 Evolutionary Genetics

    E-print Network

    Innes, David J.

    individuals Facultative sexual/asexual sexual + vegetative reproduction Sexual ­ high genotypic diversity connections among more distantly related taxa Sexual reproduction + genetic variation = large amount unique individuals Asexual clones of genetically identicalAsexual clones of genetically identical

  9. Molecular genetics of gliomas.

    PubMed

    Appin, Christina L; Brat, Daniel J

    2014-01-01

    Diffusely infiltrating gliomas are the most common primary brain tumors and include astrocytomas, oligodendrogliomas, and oligoastrocytomas of grades II and III and glioblastoma (GBM), grade IV. Histologic classification is increasingly aided by molecular genetic studies, which assist in the diagnosis and provide prognostic and predictive value. Mutations in IDH1 are frequent in grades II and III astrocytomas, oligodendrogliomas, and oligoastrocytomas, as well as secondary GBMs. IDH1-mutated diffuse gliomas are distinct from their IDH1 wild-type counterparts based on clinical features, growth rates, and concurrent genomic alterations. Grades II and III astrocytomas, as well as secondary GBMs are characterized by IDH1, TP53, and ATRX mutations, whereas oligodendrogliomas most frequently harbor codeletion of 1p/19q and mutations in CIC, FUBP1, and the TERT promoter. Primary GBMs frequently show molecular alterations in EGFR, PDGFRA, PTEN, TP53, NF1, and CDKN2A/B, as well as TERT promoter mutations, but not IDH mutations. Pediatric GBMs have a distinctive molecular pathogenesis, as H3F3A and DAXX mutations are frequent, and their gene expression profile is different than adult GBMs. Other lower-grade gliomas of childhood, such as pilocytic astrocytoma and pleomorphic xanthoastrocytoma, are characterized by BRAF mutations or activating gene rearrangements involving BRAF. PMID:24445767

  10. Genetic kidney diseases

    PubMed Central

    Hildebrandt, Friedhelm

    2010-01-01

    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

  11. Genetics Home Reference: Chordoma

    MedlinePLUS

    ... people use for chordoma? CHDM chordocarcinoma chordoepithelioma notochordal sarcoma notochordoma For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming ...

  12. Changes in Mothers' Experiences of Receiving an Autism Diagnosis: A Contextualized Case Study

    ERIC Educational Resources Information Center

    Hornstein, Shana

    2011-01-01

    Autism has a unique history. The definition has broadened and changed over time, from an emotional disturbance with psychogenic origins to a neurodevelopmental disability with suspected environmental and genetic origins. Diagnosis occurs later than children born with obvious disabilities such as cerebral palsy or Down syndrome, but earlier than…

  13. Myxoinflammatory fibroblastic sarcoma: morphologic and genetic updates.

    PubMed

    Ieremia, Eleni; Thway, Khin

    2014-10-01

    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

  14. Age at Diagnosis of Sickle Cell Anaemia in Lagos, Nigeria

    PubMed Central

    Akodu, SO; Diaku-Akinwumi, IN; Njokanma, OF

    2013-01-01

    Background Sickle cell anaemia is the most common genetic disorder worldwide as well as in Nigeria. Delay in the diagnosis of the condition constitutes an important cause of concern for caretakers of affected children. Objective To determine the age at diagnosis in a population of children with sickle cell anaemia in Lagos, Nigeria. Methodology The study was conducted between October and December 2009 at the sickle cell clinic of the Department of Paediatrics of Lagos State University Teaching Hospital, Ikeja, Lagos in South west Nigeria. By convenience sampling, a total of 192 children with sickle cell anaemia aged six months to 15 years were interviewed with the aid of a structured questionnaire. Results Overall, the mean age at confirmation of haemoglobin genotype was 27.33 months (± 26. 36 months). The mean age at diagnosis was significantly lower among males than females (25.59 ± 27.74 Vs. 29.14 ± 24.85, p = 0.04). A quarter of the children were diagnosed before infancy and three-quarters before three years of age. Upper social stratum and small family size were significantly associated with earlier diagnosis of sickle cell anaemia. Conclusion Too few subjects are diagnosed in infancy. Routine screening should ideally be done at birth and neonatal period or at the latest, between six and nine months. PMID:23350014

  15. Biology 2250 Principles of Genetics

    E-print Network

    Innes, David J.

    ? - Genetics is the study of heredity and variation - Examples of genetic variation 1. Domesticated species 2 American J. Human Genetics Heredity Annals of Human Genetics Hereditas Opthalmic Genetics Japanese Journal of Human Genetics Human Genetics Journal of Heredity CurrentGenetics Molecular Biology and Evolution Animal

  16. Disorders and borders: psychiatric genetics and nosology.

    PubMed

    Smoller, Jordan W

    2013-10-01

    Over the past century, the definition and classification of psychiatric disorders has evolved through a combination of historical trends, clinical observations, and empirical research. The current nosology, instantiated in the DSM-5 and ICD-10, rests on descriptive criteria agreed upon by a consensus of experts. While the development of explicit criteria has enhanced the reliability of diagnosis, the validity of the current diagnostic categories has been the subject of debate and controversy. Genetic studies have long been regarded as a key resource for validating the boundaries among diagnostic categories. Genetic epidemiologic studies have documented the familiality and heritability of clinically defined psychiatric disorders and molecular genetic studies have begun to identify specific susceptibility variants. At the same time, there is growing evidence from family, twin and genomic studies that genetic influences on psychiatric disorders transcend clinical boundaries. Here I review this evidence for cross-disorder genetic effects and discuss the implications of these findings for psychiatric nosology. Psychiatric genetic research can inform a bottom-up reappraisal of psychopathology that may help the field move beyond a purely descriptive classification and toward an etiology-based nosology. PMID:24132891

  17. Genetic Syndromes associated with Congenital Heart Disease

    PubMed Central

    2015-01-01

    Recent research has demonstrated that genetic alterations or variations contribute considerably to the development of congenital heart disease. Many kinds of genetic tests are commercially available, and more are currently under development. Congenital heart disease is frequently accompanied by genetic syndromes showing both cardiac and extra-cardiac anomalies. Congenital heart disease is the leading cause of birth defects, and is an important cause of morbidity and mortality during infancy and childhood. This review introduces common genetic syndromes showing various types of congenital heart disease, including Down syndrome, Turner syndrome, 22q11 deletion syndrome, Williams syndrome, and Noonan syndrome. Although surgical techniques and perioperative care have improved substantially, patients with genetic syndromes may be at an increased risk of death or major complications associated with surgery. Therefore, risk management based on an accurate genetic diagnosis is necessary in order to effectively plan the surgical and medical management and follow-up for these patients. In addition, multidisciplinary approaches and care for the combined extra-cardiac anomalies may help to reduce mortality and morbidity accompanied with congenital heart disease. PMID:26413101

  18. Laser mass spectrometry for DNA sequencing, disease diagnosis, and fingerprinting

    SciTech Connect

    Winston Chen, C.H.; Taranenko, N.I.; Zhu, Y.F.; Chung, C.N.; Allman, S.L.

    1997-03-01

    Since laser mass spectrometry has the potential for achieving very fast DNA analysis, the authors recently applied it to DNA sequencing, DNA typing for fingerprinting, and DNA screening for disease diagnosis. Two different approaches for sequencing DNA have been successfully demonstrated. One is to sequence DNA with DNA ladders produced from Snager`s enzymatic method. The other is to do direct sequencing without DNA ladders. The need for quick DNA typing for identification purposes is critical for forensic application. The preliminary results indicate laser mass spectrometry can possibly be used for rapid DNA fingerprinting applications at a much lower cost than gel electrophoresis. Population screening for certain genetic disease can be a very efficient step to reducing medical costs through prevention. Since laser mass spectrometry can provide very fast DNA analysis, the authors applied laser mass spectrometry to disease diagnosis. Clinical samples with both base deletion and point mutation have been tested with complete success.

  19. Laser mass spectrometry for DNA sequencing, disease diagnosis, and fingerprinting

    NASA Astrophysics Data System (ADS)

    Chen, C. H. Winston; Taranenko, N. I.; Zhu, Y. F.; Chung, C. N.; Allman, S. L.

    1997-05-01

    Since laser mass spectrometry has the potential for achieving very fast DNA analysis, we recently applied it to DNA sequencing, DNA typing for fingerprinting, and DNA screening for disease diagnosis. Two different approaches for sequencing DNA have been successfully demonstrated. One is to sequence DNA with DNA ladders produced from Sanger's enzymatic method. The other is to do direct sequencing without DNA ladders. The need for quick DNA typing for identification purposes is critical for forensic application. Our preliminary results indicate laser mass spectrometry can possible be used for rapid DNA fingerprinting applications at a much lower cost than gel electrophoresis. Population screening for certain genetic disease can be a very efficient step to reducing medical costs through prevention. Since laser mass spectrometry can provide very fast DNA analysis, we applied laser mass spectrometry to disease diagnosis. Clinical samples with both base deletion and point mutation have been tested with complete success.

  20. An update on immunopathogenesis, diagnosis, and treatment of multiple sclerosis

    PubMed Central

    Garg, Neeta; Smith, Thomas W

    2015-01-01

    Background Multiple sclerosis is an acquired demyelinating disease of the central nervous system. It is the second most common cause of disability in adults in United States after head trauma. Discussion The etiology of MS is probably multifactorial, related to genetic, environmental, and several other factors. The pathogenesis is not fully understood but is believed to involve T-cell-mediated inflammation directed against myelin and other related proteins with a possible role for B cells. The McDonald criteria have been proposed and revised over the years to guide the diagnosis of MS and are based on clinical presentation and magnetic resonance imaging (MRI) of the brain and spinal cord to establish dissemination in time and space. The treatment of MS includes disease modification with immunomodulator drugs and symptom management to address the specific symptoms such as fatigue, spasticity, and pain. Conclusion An update on etiology, pathogenesis, diagnosis, and immunomodulatory treatment of MS is presented. PMID:26445701

  1. Restless Leg Syndrome: A Neglected Diagnosis

    PubMed Central

    Einollahi, Behzad; Izadianmehr, Neda

    2014-01-01

    Context: Restless legs syndrome (RLS) is an irresistible urge to move legs that usually occur during inactivity and at night. This neurologic condition is associated with increased risk of nocturnal hypertension as well as cardiovascular events and affects patient’s sleep, which leads to anxiety, depression, and decreases quality of life. Presence of RLS in patients on hemodialysis is associated with higher mortality rate. Most of the times, patients have indescribable symptoms. The aim of this review was to provide physicians with information to be aware and turn their attention to the patient’s symptoms, which are the most important clue to diagnosis of RLS. Evidence Acquisition: For data extraction, we reviewed PubMed, Scopus, Google scholar, the Cochrane collaboration, and Up to Date databases with the keywords of restless legs syndrome, sleep disorders, and end-stage renal disease (ESRD). The most recent review articles, clinical trials, and cross-sectional studies with large sample sizes that had used International RLS Study Group criteria (IRLSSG) and had focused on demographic characteristics and renal function were included. This situation has described in primary and secondary forms. The former usually occurs in younger patients and seems to have genetic tendencies and the latter is due to the iron deficiency state, pregnancy, and ESRD. Results: Two major theories are developed regarding the pathophysiology of RLS. The first one concerns central nervous system dopamine imbalance and the second one concerns intracellular iron dysregulation. The most common used pharmacologic agents in treatment of RLS are dopamine agonists. Other used therapeutic agents include levodopa, Alpha-2-delta calcium channel ligands, opioids, anticonvulsants, benzodiazepines, clonidine, iron therapy in low levels of serum ferritin, and nonpharmacologic therapies. Conclusions: The most important factor in diagnosis is physician’s attention and clinical experience with this condition and using IRLSSG. PMID:25695039

  2. ["Designer baby" changed to French for "double hope baby"].

    PubMed

    Fagniez, P-L; Loriau, J; Tayar, C

    2005-10-01

    Scientific advances during the last decades regarding potential intervention on embryos arouse many questions in society to prepare the ground concerning the limits that should be set for these practices. For the first time in 1994, a parliamentary proceeding allowed the definition of a French model of bioethics through laws of the same name. These laws, among others, authorized in a well and strictly defined setting the practice of preimplantation genetic diagnosis (PGD). Because of technical progress concerning PGD, new questions arose, especially concerning the accomplishment of designer babies. The French Chamber of Representatives came in with a new law that banishes the concept of designer babies and replaces it with another concept: double hope babies, in French "bébé du double espoir". A first hope of a pregnancy giving birth to a healthy child and the second being that this child conceived with the aid of PGD could help treat an elder brother. Because of the issuing of two specific laws in a ten years interval, France occupies a privileged place in a Europe where bioethical issues continue to be debated, particularly PGD. PMID:16139550

  3. Wide range of chromosome abnormalities in the embryos of young egg donors.

    PubMed

    Munné, S; Ary, J; Zouves, C; Escudero, T; Barnes, F; Cinioglu, C; Ary, B; Cohen, J

    2006-03-01

    Embryo chromosome studies show high rates of abnormalities, above 50%, but most embryos studied were from patients aged 35 and older. The objectives of this study were firstly, to evaluate the rate of chromosome abnormalities in embryos from young egg donors, and secondly, to compare the range of chromosome abnormality rates between donors and non-egg donor cycles, both undergoing preimplantation genetic diagnosis (PGD) for infertility using fluorescence in-situ hybridization analysis with probes for chromosomes X, Y, 13, 15, 16, 18, 21, and 22. On average, only 43% of the embryos were chromosomally normal, while the comparison group had euploidy rates between 34 (age group 18-34) (P < 0.001) and 21% (age group 40-45) (P < 0.001). There was considerable variation between donor cycles, with almost one-third having less than 30% normal embryos. Also, within donors and recipients repeating several IVF cycles with PGD, only 29-56% of the second PGD cycles had similar rates of normal embryos to the first cycle, while in the comparison group it was 64%. The results can explain why some egg donors are successful whereas others are not, and may also show that a policy of PGD for first time egg donors is appropriate and indicated. PMID:16569324

  4. The role of imaging in the diagnosis and management of hypertrophic cardiomyopathy.

    PubMed

    Weissler-Snir, Adaya; Crean, Andrew; Rakowski, Harry

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy, affecting approximately 1:500 people. As the yield of genetic testing is only about 35-60%, the diagnosis of HCM is still clinical and based on the demonstration of unexplained and usually asymmetric left ventricular (LV) hypertrophy by imaging modalities. In the past, echocardiography was the sole imaging modality used for the diagnosis and management of HCM. However, in recent years other imaging modalities such as cardiac magnetic resonance have played a major role in the diagnosis, management and risk stratification of HCM, particularly when the location of left ventricular hypertrophy is atypical (apex, lateral wall) and when the echocardiographic imaging is sub-optimal. However, the most unique contribution of cardiac magnetic resonance is the quantification of myocardial fibrosis. Exercise stress echocardiography is the preferred provocative test for the assessment of LV outflow tract obstruction, which is detected only on provocation in one-third of the patients. PMID:26567960

  5. Evaluation of Molecular and Immunohistochemical Adjunct Modalities in the Diagnosis of Soft Tissue Neoplasms.

    PubMed

    Mourtzoukou, Despoina; Fisher, Cyril; Thway, Khin

    2015-12-01

    The accurate diagnosis of soft tissue neoplasms has crucial therapeutic and prognostic importance. There is frequent morphologic overlap between entities, and ancillary modalities are used in the vast majority of diagnoses. Immunohistochemistry is rapid and inexpensive, and in addition to the older markers that mainly detected cytoplasmic proteins, antibodies can indirectly detect tumor-specific genetic and molecular abnormalities. The use of molecular diagnostic techniques is now widespread, with molecular services often integrated into routine histopathology laboratories; as their cost and turnaround times begin to parallel those for immunohistochemistry, we compared the usefulness of ancillary immunohistochemistry, molecular genetic, and molecular cytogenetic techniques in the diagnosis of soft tissue lesions. We evaluated the number and contribution of immunohistochemical tests and panels and of ancillary molecular techniques in the primary histopathologic diagnosis of 150 soft tissue lesions. Ninety of 150 cases required either only one immunohistochemical panel or minimal immunohistochemistry for diagnosis, while 39/150 required 2 to 4 panels. In 5/150, ancillary molecular tests alone (without immunohistochemistry) were diagnostically sufficient. The majority of cases required one immunohistochemical panel for diagnosis, with a smaller proportion requiring a second, and a minority requiring a third or fourth (which mainly comprised neoplasms for which the final diagnosis was uncertain). Certain neoplasms required both extensive immunohistochemistry and ancillary molecular testing, despite which the final diagnosis was inconclusive. Ancillary molecular techniques now make a significant contribution to soft tissue tumor diagnosis, being required in over one third (52/150) of cases, and were useful in confirming or excluding tumors that were not possible to conclusively diagnose with histology and immunohistochemistry. Only a small proportion of soft tissue neoplasms (16/150; all benign) did not require immunohistochemistry or ancillary molecular methods, with morphology alone being sufficient for diagnosis. PMID:26310271

  6. November 20, 2001 Evolutionary Genetics

    E-print Network

    Gavrilets, Sergey

    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

  7. [Diagnosis of tuberous sclerosis complex].

    PubMed

    Belousova, E D; Dorofeeva, M Yu; Pivovarova, A M; Katusheva, O V

    2015-01-01

    Tuberous sclerosis complex is a autosomal dominant instantly progressing disease, causing the development of benign tumors in all organs and tissues of human body. According to International Consensus Conference (2012), definite or possible TSC diagnosis can be made. For the definite diagnosis of TSC, two major criteria or one major criterion and ?2 minor criteria have to be present. For a possible diagnosis, 1 major criterion or ?2 minor criteria should be found. A pathogenic mutation in the TSC1 or TSC2 gene is by itself sufficient for a definite diagnosis. There are following major diagnostic criteria: angiofibromas (?3) or forehead plaque; hypomelanotic macules (?3); ungual fibromas (?2); chagrin patch; multiple retinal hamartomas; cortical dysplasias (?3, include tubers and cerebral white matter radial migration lines; subependymal nodules; subependymal giant cell astrocytoma; cardiac rhabdomyoma; lymphagioleiomatosis and renal angiomyolipomas (?2). The minor criteria are the following ones: dental enamel pits (?3); intraoral fibromas (?2); non-renal hamartomas; retinal achromatic patch; confetti skin lesions; multiple renal cysts. Diagnosis of TSC is not difficult if a physician is familiar with clinical presentation of the disease. PMID:26525630

  8. Safe, accurate, prenatal diagnosis of thanatophoric dysplasia using ultrasound and free fetal DNA

    PubMed Central

    Chitty, Lyn S; Khalil, Asma; Barrett, Angela N; Pajkrt, Eva; Griffin, David R; Cole, Tim J

    2013-01-01

    Objective To improve the prenatal diagnosis of thanatophoric dysplasia by defining the change in fetal size across gestation and the frequency of sonographic features, and developing non-invasive molecular genetic diagnosis based on cell-free fetal DNA (cffDNA) in maternal plasma. Methods Fetuses with a confirmed diagnosis of thanatophoric dysplasia were ascertained, records reviewed, sonographic features and measurements determined. Charts of fetal size were then constructed using the LMS (lambda-mu-sigma) method and compared with charts used in normal pregnancies and those complicated by achondroplasia. Cases in this cohort referred to our Regional Genetics Laboratory for molecular diagnosis using cffDNA were identified and results reviewed. Results Forty-two cases were scanned in our units. Commonly reported sonographic features were very short and sometimes bowed femora, frontal bossing, cloverleaf skull, short fingers, a small chest and polyhydramnios. Limb shortening was obvious from as early as 13 weeks' gestation, with minimal growth after 20 weeks. Analysis of cffDNA in three of these pregnancies confirmed the presence of the c.742C>CT (p.Arg248Cys) or the c.1948A>AG (p.Lys650Glu) mutation in the fibroblast growth factor receptor 3 gene. Conclusion These data should improve the accuracy of the sonographic diagnosis of thanatophoric dysplasia and have implications for reliable and safe targeted molecular confirmation using cffDNA. © 2013 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. PMID:23408600

  9. Databases for genetic services. Current usages and future directions.

    PubMed

    Meaney, F J

    1987-06-01

    Computer-based systems for the management of data in clinical genetics have become increasingly available for patient information storage and retrieval, evaluation and diagnosis, and pedigree data. The need for a national genetic services database has been recognized, and federal grants have provided funds for the development of state and regional databases for the evaluation of genetic services. Continuation of federal funding and the development of data systems that allow local, state, and regional needs to be met are essential for any progress to be made toward a national database. PMID:3668409

  10. The Genetics of Reading Disabilities: From Phenotypes to Candidate Genes

    PubMed Central

    Raskind, Wendy H.; Peter, Beate; Richards, Todd; Eckert, Mark M.; Berninger, Virginia W.

    2013-01-01

    This article provides an overview of (a) issues in definition and diagnosis of specific reading disabilities at the behavioral level that may occur in different constellations of developmental and phenotypic profiles (patterns); (b) rapidly expanding research on genetic heterogeneity and gene candidates for dyslexia and other reading disabilities; (c) emerging research on gene-brain relationships; and (d) current understanding of epigenetic mechanisms whereby environmental events may alter behavioral expression of genetic variations. A glossary of genetic terms (denoted by bold font) is provided for readers not familiar with the technical terms. PMID:23308072

  11. Genetics and the investigation of developmental delay/intellectual disability.

    PubMed

    Srour, Myriam; Shevell, Michael

    2014-04-01

    Global developmental delay and intellectual disabilities are common reasons for diagnostic assessment by paediatricians. There are a multiplicity of possible causes many of which have genetic, management and treatment implications for the child and family. Genetic causes are estimated to be responsible for approximately a quarter to one-half of identified cases. The multiplicity of individually rare genetic causes challenges the practitioner with respect to the selection of diagnostic tests and accurate diagnosis. To assist the practitioner practice guidelines have been formulated and these are reviewed and summarised in this particular article. PMID:24344174

  12. Human genetics in Johannesburg, South Africa: past, present and future.

    PubMed

    Kromberg, Jennifer G R; Krause, Amanda

    2013-12-01

    Genetic services were set up in Johannesburg, South Africa, in the late 1960s, but only became widespread and formalised after the first Professor of Human Genetics, Trefor Jenkins, was installed at the University of the Witwatersrand in 1974. The first services involved chromosome studies, and these developed into genetic counselling services. Prenatal diagnosis began to be offered, particularly for older women at risk for chromosome abnormalities in the fetus, and those at risk for neural tube defects. Genetic screening was then initiated for the Jewish community because of their high carrier rate for Tay-Sachs disease. Educational courses in human genetics were offered at Wits Medical School, and medical as well as other health professionals began to be trained. Research, supported by national and international bodies, was integral in the activities of the Department (now Division) of Human Genetics and focused on genetic conditions affecting the generally understudied black community. In the late 1980s the first training programme for genetic counsellors was started at MSc level, and postgraduate scientists at MSc and PhD levels studied in and qualified through the Department. At the same time molecular genetic laboratories were set up. In the late 1990s training for medical geneticists was initiated. Extensive high-quality genetic services developed over the four decades were comparable to those of most other departments in developed countries.  PMID:24300637

  13. Unified Criteria for Ultrasonographic Diagnosis of ADPKD

    PubMed Central

    Pei, York; Obaji, James; Dupuis, Annie; Paterson, Andrew D.; Magistroni, Riccardo; Dicks, Elizabeth; Parfrey, Patrick; Cramer, Benvon; Coto, Eliecer; Torra, Roser; San Millan, Jose L.; Gibson, Robert; Breuning, Martijn; Peters, Dorien; Ravine, David

    2009-01-01

    Individuals who are at risk for autosomal dominant polycystic kidney disease are often screened by ultrasound using diagnostic criteria derived from individuals with mutations in PKD1. Families with mutations in PKD2 typically have less severe disease, suggesting a potential need for different diagnostic criteria. In this study, 577 and 371 at-risk individuals from 58 PKD1 and 39 PKD2 families, respectively, were assessed by renal ultrasound and molecular genotyping. Using sensitivity data derived from genetically affected individuals and specificity data derived from genetically unaffected individuals, various diagnostic criteria were compared. In addition, data sets were created to simulate the PKD1 and PKD2 case mix expected in practice to evaluate the performance of diagnostic criteria for families of unknown genotype. The diagnostic criteria currently in use performed suboptimally for individuals with mutations in PKD2 as a result of reduced test sensitivity. In families of unknown genotype, the presence of three or more (unilateral or bilateral) renal cysts is sufficient for establishing the diagnosis in individuals aged 15 to 39 y, two or more cysts in each kidney is sufficient for individuals aged 40 to 59 y, and four or more cysts in each kidney is required for individuals ?60 yr. Conversely, fewer than two renal cysts in at-risk individuals aged ?40 yr is sufficient to exclude the disease. These unified diagnostic criteria will be useful for testing individuals who are at risk for autosomal dominant polycystic kidney disease in the usual clinical setting in which molecular genotyping is seldom performed. PMID:18945943

  14. Age-Related Macular Degeneration: Advances in Management and Diagnosis

    PubMed Central

    Yonekawa, Yoshihiro; Miller, Joan W.; Kim, Ivana K.

    2015-01-01

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies. PMID:26239130

  15. Diagnosis of Atopic Dermatitis: Mimics, Overlaps, and Complications

    PubMed Central

    Siegfried, Elaine C.; Hebert, Adelaide A.

    2015-01-01

    Atopic dermatitis (AD) is one of the most common skin diseases affecting infants and children. A smaller subset of adults has persistent or new-onset AD. AD is characterized by pruritus, erythema, induration, and scale, but these features are also typical of several other conditions that can mimic, coexist with, or complicate AD. These include inflammatory skin conditions, infections, infestations, malignancies, genetic disorders, immunodeficiency disorders, nutritional disorders, graft-versus-host disease, and drug eruptions. Familiarity of the spectrum of these diseases and their distinguishing features is critical for correct and timely diagnosis and optimal treatment. PMID:26239454

  16. With current gene markers, presymptomatic diagnosis of heritable disease is still a family affair

    SciTech Connect

    Not Available

    1987-09-04

    In the last four years, genes or genetic markers have been identified for a host of disorders including Huntington's disease, cystic fibrosis, Duchenne muscular dystrophy, polycystic kidney disease, bipolar depressive disorder, retinoblastoma, Alzheimer's disease, and schizophrenia. Such discoveries have made it possible to diagnose in utero some 30 genetic diseases during the first trimester of pregnancy. Yet, while these newly discovered gene markers may be revolutionizing prenatal and presymptomatic diagnosis, they are in many respects halfway technology. Such was the opinion of several speakers at a conference sponsored by the American Medical Association in Washington, DC. At the conference, entitled DNA Probes in the Practice of Medicine, geneticists emphasized that gene markers - stretches of DNA that are usually inherited in tandem with a disease gene - are usually not sufficient for presymptomatic diagnosis of genetic disease in an individual.

  17. Cancer Genetics Services Directory

    MedlinePLUS

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  18. Frontotemporal Dementia: Genetics

    MedlinePLUS

    ... of Genetic Counselors at www.nsgc.org . A genetic counselor or geneticist develops a family pedigree, which is a graphic description of family tree with health history, to record information collected from patients and families. ... possibility of genetic testing with your genetic counselor or doctor. You ...

  19. Biology 4250 Evolutionary Genetics

    E-print Network

    Innes, David J.

    1 Biology 4250 Evolutionary Genetics Fall 2009 Dr David InnesDr. David Innes Course Webpage: http in Genetic Variation 2. Types of Molecular Markers 3. Molecular Markers in Ecology and Evolution 4 I di id and Evolution 9. Conservation Genetics 10. Human Evolutionary Genetics Darwin and evolution: conversion

  20. Biology 4250 Evolutionary Genetics

    E-print Network

    Innes, David J.

    1 Biology 4250 Evolutionary Genetics Fall 2009 Dr. David Innes Outline of topics: 1. Introduction/History of Interest in Genetic Variation 2. Types of Molecular Markers 3. Molecular Markers in Ecology and Evolution 4 8. Sex and Evolution 9. Conservation Genetics 10. Human Evolutionary Genetics Advantages

  1. Inspirations in medical genetics.

    PubMed

    Asadollahi, Reza

    2014-03-21

    There are abundant instances in the history of genetics and medical genetics to illustrate how curiosity, charisma of mentors, nature, art, the saving of lives and many other matters have inspired great discoveries. These achievements from deciphering genetic concepts to characterizing genetic disorders have been crucial for management of the patients. There remains, however, a long pathway ahead. PMID:24658215

  2. Genetic Counseling Program Information

    E-print Network

    Berdichevsky, Victor

    Genetic Counseling Program Information for Potential Applicants #12;Page 2 of 12 8.24.11 Program Overview "Genetic counseling is the process of helping people understand and adapt to the medical of Genetic Counselors Definition Task Force. Journal of Genetic Counseling (2006); 15(2):77-83. The practice

  3. Diagnosis and Management of Behavioral Variant Frontotemporal Dementia

    PubMed Central

    Pressman, Peter; Miller, Bruce L

    2014-01-01

    Frontotemporal dementia (FTD) was documented over a century ago. The last decade, however, has seen substantial changes in our conceptions of this increasingly recognized disorder. Different clinical variants have been delineated, the most common of which is the behavioral variant (bvFTD). Updated diagnostic criteria have been established. New histopathological findings and genetic etiologies have been discovered. Research continues to uncover molecular mechanisms by which abnormal proteins accumulate in degenerating brain tissue. Novel neuroimaging techniques suggest that functional networks are diminished in bvFTD that may be relevant to empathy and social behavior. Despite rapid advances in our understanding of bvFTD, the disease is still under-recognized and commonly misdiagnosed. The result is inappropriate patient care. Recognizing the various presentations of bvFTD and its histological and genetic subtypes may further diagnosis, treatment and research. PMID:24315411

  4. Etiology of Attention Disorders: A Neurological/Genetic Perspective.

    ERIC Educational Resources Information Center

    Grantham, Madeline Kay

    This paper explores the historical origins of attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD) as a neurological disorder, current neurological and genetic research concerning the etiology of ADD/ADHD, and implications for diagnosis and treatment. First, ADD/ADHD is defined and then the origins of ADD/ADHD as a…

  5. Current understanding of genetics and genetic testing and information needs and preferences of adults with inherited retinal disease.

    PubMed

    McKibbin, Martin; Ahmed, Mushtaq; Allsop, Matthew J; Downey, Louise; Gale, Richard; Grant, Hilary Louise; Potrata, Barbara; Willis, Thomas A; Hewison, Jenny

    2014-09-01

    Advances in sequencing technology and the movement of genetic testing into all areas of medicine will increase opportunities for molecular confirmation of a clinical diagnosis. For health-care professionals without formal genetics training, there is a need to know what patients understand about genetics and genetic testing and their information needs and preferences for the disclosure of genetic testing results. These topics were explored during face-to-face interviews with 50 adults with inherited retinal disease, selected in order to provide a diversity of opinions. Participants had variable understanding of genetics and genetic testing, including basic concepts such as inheritance patterns and the risk to dependents, and many did not understand the term 'genetic counselling'. Most were keen for extra information on the risk to others, the process for genetic testing and how to share the information with other family members. Participants were divided as to whether genetic testing should be offered at the time of the initial diagnosis or later. Many would prefer the results to be given by face-to-face consultation, supplemented by further information in a format accessible to those with visual impairment. Health-care professionals and either leaflets or websites of trusted agencies were the preferred sources of information. Permission should be sought for disclosure of genetic information to other family members. The information needs of many patients with inherited retinal disease appear to be unmet. An understanding of their information needs and preferences is required to help health-care professionals provide optimal services that meet patient expectations. PMID:24398793

  6. ADHD: Is Objective Diagnosis Possible?

    PubMed Central

    Johnson, Lynda G.

    2005-01-01

    Although attention deficit/hyperactivity disorder (ADHD) is one of the most common cognitive disorders, the usual diagnostic procedures pursued by psychiatrists, neurologists, pediatricians, and family practitioners are based largely, if not exclusively, on subjective assessments of perceived behavior. The recommended approaches to ADHD diagnosis are reviewed, first from the perspective of the various expert panels, and then from the research literature upon which those recommendations are based. The authors agree that ADHD is a clinical diagnosis, and that the assessment of subjective reports can be systematic. But they propose that objective data should also contribute to the clinical diagnosis of ADHD; and that new computerized assessment technology can generate objective cognitive data in an efficient and cost-effective way. Computerized tests can also improve the assessment of treatment response over time. PMID:21120096

  7. [Asperger syndrome - a fashionable diagnosis?].

    PubMed

    Haker, Helene

    2014-10-01

    The Asperger Syndrome is - in contrast to early childhood autism - a disorder at the lighter end of the autism spectrum. Although first described in 1943, it was included in the ICD-10 not before 1992. The knowledge about this lighter autistic disorder spread only slowly. The increasing prevalence rates can be explained by the increased knowledge about this disorder and the growing clinical experience. In contrast to the public that gives repeated medial attention to it, and to would-be affected who seem to see an attractive excuse for social problems in an Asperger diagnosis, many psychiatrists appear cautious to state a diagnosis with which they are not familiar and which is discredited as a fashionable diagnosis. PMID:25270748

  8. Diagnosis of human visceral pentastomiasis.

    PubMed

    Tappe, Dennis; Büttner, Dietrich W

    2009-01-01

    Visceral pentastomiasis in humans is caused by the larval stages (nymphs) of the arthropod-related tongue worms Linguatula serrata, Armillifer armillatus, A. moniliformis, A. grandis, and Porocephalus crotali. The majority of cases has been reported from Africa, Malaysia, and the Middle East, where visceral pentastomiasis may be an incidental finding in autopsies, and less often from China and Latin America. In Europe and North America, the disease is only rarely encountered in immigrants and long-term travelers, and the parasitic lesions may be confused with malignancies, leading to a delay in the correct diagnosis. Since clinical symptoms are variable and serological tests are not readily available, the diagnosis often relies on histopathological examinations. This laboratory symposium focuses on the diagnosis of this unusual parasitic disease and presents its risk factors and epidemiology. PMID:19238218

  9. Diagnosis of Human Visceral Pentastomiasis

    PubMed Central

    Tappe, Dennis; Büttner, Dietrich W.

    2009-01-01

    Visceral pentastomiasis in humans is caused by the larval stages (nymphs) of the arthropod-related tongue worms Linguatula serrata, Armillifer armillatus, A. moniliformis, A. grandis, and Porocephalus crotali. The majority of cases has been reported from Africa, Malaysia, and the Middle East, where visceral pentastomiasis may be an incidental finding in autopsies, and less often from China and Latin America. In Europe and North America, the disease is only rarely encountered in immigrants and long-term travelers, and the parasitic lesions may be confused with malignancies, leading to a delay in the correct diagnosis. Since clinical symptoms are variable and serological tests are not readily available, the diagnosis often relies on histopathological examinations. This laboratory symposium focuses on the diagnosis of this unusual parasitic disease and presents its risk factors and epidemiology. PMID:19238218

  10. Charcot-Marie-Tooth disease variants-classification, clinical, and genetic features and rational diagnostic evaluation.

    PubMed

    Bassam, Bassam A

    2014-03-01

    Inherited neuropathies are among the most prevalent inherited neurologic disorders, and with current advances in molecular biology and genetic testing, the clinical spectrum of phenotype/genotype has been expanding enormously. Genetic testing is nowadays commercially available to several subtypes although many remain because of unknown genetic defect. A stepwise rational approach, which is shown in , facilitates reaching a specific diagnosis and reduces the cost. PMID:24534835

  11. Diagnosis of alcoholic liver disease

    PubMed Central

    Torruellas, Cara; French, Samuel W; Medici, Valentina

    2014-01-01

    Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential. PMID:25206273

  12. Autism Diagnosis and Screening: Factors to Consider in Differential Diagnosis

    ERIC Educational Resources Information Center

    Matson, Johnny L.; Beighley, Jennifer; Turygin, Nicole

    2012-01-01

    There has been an exponential growth in assessment methods to diagnose disorders on the autism spectrum. Many reasons for this trend exist and include advancing knowledge on how to make a diagnosis, the heterogeneity of the spectrum, the realization that different methods may be needed based on age and intellectual disability. Other factors…

  13. [Difficult diagnosis in pulmonary hydatidosis].

    PubMed

    Pop, Monica; Mure?an, Alina; Râjnoveanu, Ruxandra; Man, Milena

    2006-01-01

    Echinococcosis is a disease caused by a small taenid-tape of Echinococcus granulosus, a parasite that lives in the intestine of canines. Occasionally the intermediate host is the human being and it is located especially in the liver and in the lung having the shape of cysts. The diagnosis is often difficult because of the radiological aspect of the cysts, which are very much alike some tumor. The abstract contains two cases of pulmonary hydatid cyst and its steps towards the final diagnosis. PMID:17802938

  14. Rhabdomyolysis: Pathogenesis, Diagnosis, and Treatment

    PubMed Central

    Torres, Patrick A.; Helmstetter, John A.; Kaye, Adam M.; Kaye, Alan David

    2015-01-01

    Background Rhabdomyolysis is a complex medical condition involving the rapid dissolution of damaged or injured skeletal muscle. Methods This review focuses on the epidemiology, pathophysiology, causes, presentation, diagnosis, complications, management, and anesthetic considerations related to rhabdomyolysis. Results Any form of muscle damage––and by extension any entity that causes muscle damage––can initiate rhabdomyolysis. One of the most important treatment goals when rhabdomyolysis is suspected is avoiding acute kidney injury. Conclusion All clinicians should be aware of common causes, diagnosis, and treatment options. PMID:25829882

  15. Diagnosis of amyotrophic lateral sclerosis.

    PubMed

    Rowland, L P

    1998-10-01

    This review of the differential diagnosis of amyotrophic lateral sclerosis focuses on two themes. The first is practical, how to establish the diagnosis based primarily on clinical findings buttressed by electrodiagnosis. The main considerations are multifocal motor neuropathy and cervical spondylotic myelopathy. The second theme is the relationship of motor neuron disease to other conditions, including benign fasciculation (Denny-Brown, Foley syndrome), paraneoplastic syndromes, lymphoproliferative disease, radiation damage, monomelic amyotrophy (Hirayama syndrome), as well as an association with parkinsonism, dementia and multisystem disorders of the central nervous system. PMID:9851643

  16. How do solar UV irradiance and smoking impact the diagnosis of second cancers after diagnosis of melanoma?: No answer yet.

    PubMed

    Berwick, Marianne

    2012-01-01

    It may be useful to look at the risk patterns for developing a second primary malignancy after a first primary melanoma diagnosis in order to understand the etiology and mortality due to melanoma. In this volume, W.B. Grant has proposed the interesting hypothesis that solar UV radiation and smoking may be inversely associated with the development of melanoma through the presence of dermal or solar elastosis. However, this association is inconsistent and may be explained by confounding by outdoor activity, physical exercise, obesity, diet and underlying immune or genetic factors. PMID:22870348

  17. R. D. Field TU Talk Genetic AlgorithmsGenetic Algorithms

    E-print Network

    Field, Richard

    ): · Very Slow! Genetic Algorithms (model of genetics & evolution): · Combine the good features of both y yR. D. Field TU Talk Genetic AlgorithmsGenetic Algorithms andand Neural NetworksNeural Networks asas genetics and evolution (Genetic Algorithms). · Show an example of the use of a genetic algorithm

  18. Spinocerebellar ataxia type 3/Machado-Joseph disease manifested as spastic paraplegia: A clinical and genetic study

    PubMed Central

    SONG, YANMIN; LIU, YUNHAI; ZHANG, NING; LONG, LILI

    2015-01-01

    The aim of the present study was to conduct a familial investigation and provide a genetic diagnosis to a family presenting with spastic paraplegia and clinically diagnosed with hereditary spastic paraplegia (HSP). Blood samples were obtained from the family, and mutations in the gene causing spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease (MJD), known as MJD1, were analyzed using the polymerase chain reaction, 8% denaturing polyacrylamide gel electrophoresis, and T-vector ligation and sequencing. The trinucleotide repeat number of the mutant allele was 80, leading to a genetic diagnosis of SCA3/MJD. This suggests that patients with SCA3/MJD characteristically present with typical spastic paraplegia without evident manifestations of ataxia. For those families with HSP involving the nervous system and showing genetic anticipation, an MJD1 genetic diagnosis should be considered to assist in clinical diagnosis of HSP. PMID:25574208

  19. Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment.

    PubMed

    Engel, Andrew G; Shen, Xin-Ming; Selcen, Duygu; Sine, Steven M

    2015-04-01

    The congenital myasthenic syndromes (CMS) are a diverse group of genetic disorders caused by abnormal signal transmission at the motor endplate, a special synaptic contact between motor axons and each skeletal muscle fibre. Most CMS stem from molecular defects in the muscle nicotinic acetylcholine receptor, but they can also be caused by mutations in presynaptic proteins, mutations in proteins associated with the synaptic basal lamina, defects in endplate development and maintenance, or defects in protein glycosylation. The specific diagnosis of some CMS can sometimes be reached by phenotypic clues pointing to the mutated gene. In the absence of such clues, exome sequencing is a useful technique for finding the disease gene. Greater understanding of the mechanisms of CMS have been obtained from structural and electrophysiological studies of the endplate, and from biochemical studies. Present therapies for the CMS include cholinergic agonists, long-lived open-channel blockers of the acetylcholine receptor ion channel, and adrenergic agonists. Although most CMS are treatable, caution should be exercised as some drugs that are beneficial in one syndrome can be detrimental in another. PMID:25792100

  20. Molecular Diagnosis in Autoimmune Skin Blistering Conditions

    PubMed Central

    Otten, J.V.; Hashimoto, T.; Hertl, M.; Payne, A.S.; Sitaru, C.

    2014-01-01

    Blister formation in skin and mucous membranes results from a loss of cell-cell or cell-matrix adhesion and is a common outcome of pathological events in a variety of conditions, including autoimmune and genetic diseases, viral and bacterial infections, or injury by physical and chemical factors. Autoantibodies against structural components maintaining cell-cell and cell-matrix adhesion induce tissue damage in autoimmune blistering diseases. Detection of these autoantibodies either tissue-bound or circulating in serum is essential to diagnose the autoimmune nature of disease. Various immunofluorescence methods as well as molecular immunoassays, including enzyme-linked immunosorbent assay and immunoblotting, belong to the modern diagnostic algorithms for these disorders. There is still a considerable need to increase awareness of the rare autoimmune blistering diseases, which often show a severe, chronic-relapsing course, among physicians and the public. This review article describes the immunopathological features of autoimmune bullous diseases and the molecular immunoassays currently available for their diagnosis and monitoring. PMID:24160488

  1. Genetic heterogeneity in Usher syndrome.

    PubMed

    Keats, Bronya J B; Savas, Sevtap

    2004-09-15

    Mutations in seven different genes have been associated with Usher syndrome, and an additional four loci have been mapped. The identified genes encode myosin VIIa, harmonin (a PDZ-domain protein), cadherin 23, protocadherin 15, sans (a scaffold-like protein), usherin and clarin. Three clinical types of Usher syndrome have been described: USH1 patients have severe to profound congenital hearing loss, vestibular dysfunction, and retinal degeneration beginning in childhood, those with USH2 have moderate to severe congenital hearing loss, normal vestibular function, and later onset of retinitis pigmentosa, and USH3 patients have progressive hearing loss, which distinguishes them from the other two types. The shaker-1, waltzer, Ames waltzer, and Jackson shaker mice provide murine models for four of the genetic forms of Usher syndrome. Ongoing studies are enabling early diagnosis of Usher syndrome in children who present with hearing loss, thus providing time to prepare for the onset of visual loss. PMID:15368488

  2. Diagnosis of cracked tooth syndrome

    PubMed Central

    Mathew, Sebeena; Thangavel, Boopathi; Mathew, Chalakuzhiyil Abraham; Kailasam, SivaKumar; Kumaravadivel, Karthick; Das, Arjun

    2012-01-01

    The incidences of cracks in teeth seem to have increased during the past decade. Dental practitioners need to be aware of cracked tooth syndrome (CTS) in order to be successful at diagnosing CTS. Early diagnosis has been linked with successful restorative management and predictably good prognosis. The purpose of this article is to highlight factors that contribute to detecting cracked teeth. PMID:23066261

  3. [Prenatal diagnosis of ovarian cysts].

    PubMed

    Frémond, B; Guibert, L; Jouan, H; Milon, J; Tekou, H; Duval, J M; Babut, J M

    1986-01-01

    The authors report 10 cases of ante-natally diagnosed ovarian cysts. Ultrasonography greatly contributed to the diagnosis of this condition rarely described before. These cysts are usually follicular cysts. Physiopathological explanation still remain unclear: excessive fetal gonadotrope activity, enzymatic abnormality of the theca interna, abnormal stimulation by the mother's HCG are the main hypothesis. Ultrasonographic prenatal diagnosis is based on the discovery of an intra-abdominal round liquid area in a female fetus with normal kidneys and bladder. Obstetrical management is very simple: observation and vaginal delivery. After birth, diagnosis is assessed by clinical examination and ultrasonography which may be able to recognize a possible torsion (intracystic fluid septation). Treatment is conditioned by two facts: first these cysts are usually follicular benign lesions, second there is a high risk of complications, mainly torsion or rupture. Non-operative treatment and observation can be justified for very small cysts which have low risk of torsion. Laparotomy confirms the diagnosis: regarding non complicated cysts, surgery must be as conservative as possible: cystectomy is often feasible, leaving a laminated but functional ovary. Percutaneous puncture under ultrasonography could be considered. PMID:3533290

  4. [Differential diagnosis of pigmented tumors].

    PubMed

    Hundeiker, M

    1979-05-10

    Some frequent diagnostic problems and the most important clinical and histologic criteria in differential diagnosis of malignant melanomas, benign pigment cell nevi, melanotic epithelial neoplastic lesions and frequent haemosiderotic tumors are delineated in a condensed survey. Considering the variety of diagnostic errors, one should never treat respectively destroy pigmented tumors of the skin without histologic investigation. PMID:218872

  5. Publications Fish Disease Diagnosis and

    E-print Network

    written in the Microsoft implementation of the BASIC inter preted programming language BASICA (or GW BASICPublications Fish Disease Diagnosis and Basic Fishery Computer Programs The second edition distribution of the disease and, finally, key refer ences on it. The volume is an excellent hand book

  6. DCTD — Cancer Diagnosis Program (CDP)

    Cancer.gov

    Staff from the NCI Divisions of Cancer Biology (DCB) and Cancer Treatment and Diagnosis (DCTD) along with the Lance Armstrong Foundation Live Strong Young Adult Alliance Science Task Force sponsored a joint workshop on cancer biology among adolescent and young adult (AYA) oncology patients with breast, colon, and ALL.

  7. DCTD — Cancer Diagnosis Program (CDP)

    Cancer.gov

    The goals of this conference were to bring together cancer clinicians, researchers, engineers, and public health experts from academia, clinical centers, government, and non-governmental organizations to focus on clinical aspects of cancer in the developing world and on promising technological developments for diagnosis, prognosis, and treatment.

  8. Mental Retardation: Diagnosis and Treatment.

    ERIC Educational Resources Information Center

    Poser, Charles M., Ed.

    A collection of writings by 17 authors, the text includes the following discussions: general principles of diagnosis and management of mental retardation, neurologic evaluation of the infant and child, psychological evaluation, educational information, and treatment of pseudoretardation, communicative disorders, and metabolic and endocrine causes.…

  9. Trichotillomania: Assessment, Diagnosis, and Treatment

    ERIC Educational Resources Information Center

    Kress, Victoria E. White; Kelly, Brandy L.; McCormick, Laura J.

    2004-01-01

    This article examines the assessment, diagnosis, and treatment of trichotillomania (the recurrent desire to pull out one's hair). The authors provide a brief review both of proposed etiologies of trichotillomania and of the diagnostic and assessment issues related to this disorder, and they discuss interventions and treatments that have been shown…

  10. Antenatal diagnosis of isolated omphalocele

    PubMed Central

    Lamquami, Safae; Mamouni, Nisrine; Errarhay, Sanae; Bouchikhi, Chahrazzad; Banani, Abdelaziz

    2015-01-01

    The concern of obstetric and surgical teams is when diagnosis of omphalocele, the care of the newborn and the prognosis of the malformation, mainly linked to the existence of associated malformations or chromosomal abnormalities. In our case of isolated omphalocele, the overall prognosis was good. PMID:26523175

  11. Implementation and utilization of genetic testing in personalized medicine

    PubMed Central

    Abul-Husn, Noura S; Owusu Obeng, Aniwaa; Sanderson, Saskia C; Gottesman, Omri; Scott, Stuart A

    2014-01-01

    Clinical genetic testing began over 30 years ago with the availability of mutation detection for sickle cell disease diagnosis. Since then, the field has dramatically transformed to include gene sequencing, high-throughput targeted genotyping, prenatal mutation detection, preimplantation genetic diagnosis, population-based carrier screening, and now genome-wide analyses using microarrays and next-generation sequencing. Despite these significant advances in molecular technologies and testing capabilities, clinical genetics laboratories historically have been centered on mutation detection for Mendelian disorders. However, the ongoing identification of deoxyribonucleic acid (DNA) sequence variants associated with common diseases prompted the availability of testing for personal disease risk estimation, and created commercial opportunities for direct-to-consumer genetic testing companies that assay these variants. This germline genetic risk, in conjunction with other clinical, family, and demographic variables, are the key components of the personalized medicine paradigm, which aims to apply personal genomic and other relevant data into a patient’s clinical assessment to more precisely guide medical management. However, genetic testing for disease risk estimation is an ongoing topic of debate, largely due to inconsistencies in the results, concerns over clinical validity and utility, and the variable mode of delivery when returning genetic results to patients in the absence of traditional counseling. A related class of genetic testing with analogous issues of clinical utility and acceptance is pharmacogenetic testing, which interrogates sequence variants implicated in interindividual drug response variability. Although clinical pharmacogenetic testing has not previously been widely adopted, advances in rapid turnaround time genetic testing technology and the recent implementation of preemptive genotyping programs at selected medical centers suggest that personalized medicine through pharmacogenetics is now a reality. This review aims to summarize the current state of implementing genetic testing for personalized medicine, with an emphasis on clinical pharmacogenetic testing. PMID:25206309

  12. Interstitial Lung Disease in Childhood: Clinical and Genetic Aspects

    PubMed Central

    Kitazawa, Hiroshi; Kure, Shigeo

    2015-01-01

    Interstitial lung disease (ILD) in childhood is a heterogeneous group of rare pulmonary conditions presenting chronic respiratory disorders. Many clinical features of ILD still remain unclear, making the treatment strategies mainly investigative. Guidelines may provide physicians with an overview on the diagnosis and therapeutic directions. However, the criteria used in different clinical studies for the classification and diagnosis of ILDs are not always the same, making the development of guidelines difficult. Advances in genetic testing have thrown light on some etiologies of ILD, which were formerly classified as ILDs of unknown origins. The need of genetic testing for unexplained ILD is growing, and new classification criteria based on the etiology should be adopted to better understand the disease. The purpose of this review is to give an overview of the clinical and genetic aspects of ILD in children. PMID:26512209

  13. Genetic factors in athetoid cerebral palsy.

    PubMed

    Amor, D J; Craig, J E; Delatycki, M B; Reddihough, D

    2001-11-01

    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 the literature aiming to identify instances of familial recurrence of athetoid cerebral palsy. The birth history, family history, and previous investigations of subjects with athetoid cerebral palsy were studied and subjects were clinically examined for evidence of an underlying genetic etiology. Factors suggesting a genetic cause were specifically sought, such as advanced paternal age, progression of symptoms, and associated congenital abnormalities. No subjects in the study group had similarly affected relatives, and additional features suggesting a genetic cause were not observed. A literature search identified 16 instances of familial recurrence of athetoid cerebral palsy. Familial cases were typically associated with significant spasticity, microcephaly, intellectual disability, seizures, and a lack of history of birth asphyxia, and most could be explained by either autosomal-recessive or X-linked-recessive inheritance. The genetic contribution to athetoid cerebral palsy is small, with an overall risk of recurrence in siblings of about 1%. This risk is lower than previously suggested in the literature. PMID:11732763

  14. Application of chromosome 16 markers in the differential diagnosis of neuronal ceroid-lipofuscinosis

    SciTech Connect

    Taschner, P.E.M.; Vos, N. de; Breuning, M.H.

    1995-06-05

    Accurate diagnosis of neuronal ceroid lipofuscinosis (NCL) is important for a correct prognosis of the disease and for genetic counseling. Up to now, no direct diagnostic test has been available for NCL. The clinical diagnosis is made on the basis of symptoms, neurophysiological, neuroradiological, and specific lipopigment pattern data. Recent advances in the genetics of NCL have enabled us to use polymorphic DNA markers linked to the CLN1 and CLN3 loci as a tool in the differential diagnosis of NCL. We have applied genetic analysis with polymorphic DNA markers flanking the CLN3 gene on chromosome 16 to two consanguineous families in which NCL occurs. In the first family, which is of Turkish extraction, two patients suffering from a protracted form of juvenile NCL previously had been diagnosed with juvenile NCL. Haplotypes from this family indicate that the patients and their healthy sibling are haplo-identical, suggesting that this protracted form of juvenile NCL is not linked to the CLN3 locus. In the second family, which is Moroccan origin, one patient suffers from the early juvenile variant of NCL (Lake-Cavanagh). In this family, the patient and one of the healthy siblings have identical haplotypes, excluding linkage of early juvenile NCL to the CLN3 locus on 16p12.1-11.2. Therefore, these cases from different populations demonstrate that haplotype analysis can be used as an additional method to exclude the diagnosis of juvenile NCL. 21 refs., 4 figs., 1 tab.

  15. Pre-natal counselling and diagnosis in Down's syndrome.

    PubMed

    Papp, Z

    1973-01-01

    Today Down's syndrome is recognizable on the basis of its clinical c haracteristics in infants. According to present knowledge, Down's syndr ome can be classified cytogenetically into 4 groups: regular trisomy, translocational trisomy, mosaic forms and double trisomies. Knowledge of the karyotype is used in genetic counselling for further prevention of Down's syndrome in unborn fetuses. Prenatal chromosome analyses, a form of intrauterine diagnosis, has been used in Hungary since 1968. The average incidence of Down's syndrome has been estimated at 1.5:1000 among newborns. The mother's age and genetic deviations are determinant s in whether or not the syndrome will occur. The risk of Down's syndrome increases from 1 per 1000 in mothers under 30 to 10-20 per 1000 in mothers over 45. Since risk increases with the mother's age amniocen tesis should be routinely performed in pregnancies of older mothers. In the case of trisomy verified by intrauterine diagnosis, termination of pregnancy is advised. If population cytogenetic investigations are practiced, the carriers of the balanced translocation will be revealed and within a few years there will be only 3 indications for amniocentesis: 1) in cases of mother's advanced age, 2) in cases of bala nced translocation carrier and 3) in cases of a previously affected chil d disregarding the parental karyotypes. The expected risk of Down's syn drome predictable from available data if higher than 1-5% justifies intr auterine chromosome analysis. PMID:12156379

  16. Diagnosis of primary ciliary dyskinesia*

    PubMed Central

    Olm, Mary Anne Kowal; Caldini, Elia Garcia; Mauad, Thais

    2015-01-01

    Primary ciliary dyskinesia (PCD) is a genetic disorder of ciliary structure or function. It results in mucus accumulation and bacterial colonization of the respiratory tract which leads to chronic upper and lower airway infections, organ laterality defects, and fertility problems. We review the respiratory signs and symptoms of PCD, as well as the screening tests for and diagnostic investigation of the disease, together with details related to ciliary function, ciliary ultrastructure, and genetic studies. In addition, we describe the difficulties in diagnosing PCD by means of transmission electron microscopy, as well as describing patient follow-up procedures. PMID:26176524

  17. Genetic syndromes associated with overgrowth in childhood

    PubMed Central

    2013-01-01

    Overgrowth syndromes comprise a diverse group of conditions with unique clinical, behavioral and molecular genetic features. While considerable overlap in presentation sometimes exists, advances in identification of the precise etiology of specific overgrowth disorders continue to improve clinicians' ability to make an accurate diagnosis. Among them, this paper introduces two classic genetic overgrowth syndromes: Sotos syndrome and Beckwith-Wiedemann syndrome. Historically, the diagnosis was based entirely on clinical findings. However, it is now understood that Sotos syndrome is caused by a variety of molecular genetic alterations resulting in haploinsufficiency of the NSD1 gene at chromosome 5q35 and that Beckwith-Wiedemann syndrome is caused by heterogeneous abnormalities in the imprinting of a number of growth regulatory genes within chromosome 11p15 in the majority of cases. Interestingly, the 11p15 imprinting region is also associated with Russell-Silver syndrome which is a typical growth retardation syndrome. Opposite epigenetic alterations in 11p15 result in opposite clinical features shown in Beckwith-Wiedemann syndrome and Russell-Silver syndrome. Although the exact functions of the causing genes have not yet been completely understood, these overgrowth syndromes can be good models to clarify the complex basis of human growth and help to develop better-directed therapies in the future. PMID:24904861

  18. Cutaneous and mucocutaneous leishmaniasis: Differential diagnosis, diagnosis, histopathology, and management.

    PubMed

    Handler, Marc Z; Patel, Parimal A; Kapila, Rajendra; Al-Qubati, Yasin; Schwartz, Robert A

    2015-12-01

    The diagnosis of leishmaniasis can be challenging because it mimics both infectious and malignant conditions. A misdiagnosis may lead to an unfavorable outcome. Using culture, histologic, and/or polymerase chain reaction study results, a diagnosis of leishmaniasis can be established and treatment initiated. Appropriate management requires an accurate diagnosis, which often includes identification of the specific etiologic species. Different endemic areas have varying sensitivities to the same medication, even within individual species. Species identification may be of practical value, because infections with select species have a substantial risk of visceral involvement. In addition, HIV and otherwise immunocompromised patients with leishmaniasis have a propensity for diffuse cutaneous leishmaniasis. For most New World Leishmania species, parenteral antimonial drugs remain the first line of therapy, while Old World species are easily treated with physical modalities. Historically, live organism vaccination has been used and is effective in preventing leishmaniasis, but results in an inoculation scar and an incubation period that may last for years. A more effective method of vaccination would be welcome. PMID:26568336

  19. AB025. Genome technology applications for perinatal diagnosis and fetal medicine in China

    PubMed Central

    Yang, Haitao

    2015-01-01

    China has nearly one million new born errors with inherited diseases or chromosomal abnormalities in its 20 million new born populations each year. It is a big challenge to avoid new born error with applying various new technologies in prenatal diagnosis. Rapid progress of genome technology in recent years has made it possible to diagnose subtle genetic abnormalities in a clinical setting on routine basis. These technology advances allowed for detailed genotype-phenotype correlations and the identification of the genetic basis of many congenital anomalies. Besides gene polymorphisms of folic acid detection, mutation analysis of thalassemia, classical chromosome analysis, and fluorescence in situ hybridization, etc. classical genetic testings, many new technologies were introduced to the clinic of prenatal and fetal medicine, more advanced technology such as CGH microarray analysis, exome and whole-genome sequencing (WGS) on pre- and postnatal samples of cell-free DNA has revolutionized the field of prenatal diagnosis. Especially, next generation sequencing (NGS) has rapidly adapted to prenatal diagnosis, non-invasive prenatal test (NIPT) was successfully applied into clinic with about half million of pregnant women received NIPT diagnosis in the analysis of aneuploidies and high risk for trisomy 13, 18 and 21 with successful detection rate of great than 99% so far. Currently Chinese central government already specified more than 100 hospitals to utilizing NIPT for high risk planeload fetal screening. Incorporation of these technologies in perinatal and fetal medicine has demonstrated that increased power of detecting diseases in prenatal diagnosis. It is clear that new genome technologies such as CGH array, whole-genome analysis and NIPT by NGS etc., offered more possibilities to identify various inherited diseases, genetic mutation or metabolism errors in new born population and provide more solutions to disease prevent and treatment in the field.

  20. Identification of genetic networks.

    PubMed Central

    Xiong, Momiao; Li, Jun; Fang, Xiangzhong

    2004-01-01

    In this report, we propose the use of structural equations as a tool for identifying and modeling genetic networks and genetic algorithms for searching the most likely genetic networks that best fit the data. After genetic networks are identified, it is fundamental to identify those networks influencing cell phenotypes. To accomplish this task we extend the concept of differential expression of the genes, widely used in gene expression data analysis, to genetic networks. We propose a definition for the differential expression of a genetic network and use the generalized T2 statistic to measure the ability of genetic networks to distinguish different phenotypes. However, describing the differential expression of genetic networks is not enough for understanding biological systems because differences in the expression of genetic networks do not directly reflect regulatory strength between gene activities. Therefore, in this report we also introduce the concept of differentially regulated genetic networks, which has the potential to assess changes of gene regulation in response to perturbation in the environment and may provide new insights into the mechanism of diseases and biological processes. We propose five novel statistics to measure the differences in regulation of genetic networks. To illustrate the concepts and methods for reconstruction of genetic networks and identification of association of genetic networks with function, we applied the proposed models and algorithms to three data sets. PMID:15020486