Sample records for genetic diagnosis pgd

  1. Views of Preimplantation Genetic Diagnosis (PGD) among Psychiatrists and Neurologists

    PubMed Central

    Abbate, Kristopher J.; Klitzman, Robert; Chung, Wendy K.; Ottman, Ruth; Leu, Cheng-Shiun; Appelbaum, Paul S.

    2014-01-01

    Objective As prenatal genetic testing (GT) and Preimplantation Genetic Diagnosis (PGD) use increase, providers in many specialties may play roles in patient discussions and referrals. Hence, we examined key aspects of neurologists’ and psychiatrists’ views and approaches. Study Design We surveyed attitudes and practices among 163 neurologists and 372 psychiatrists. Results 24.9% of neurologists and 31.9% of psychiatrists had discussed prenatal GT with patients, but 95.3% didn’t feel comfortable discussing PGD; only 2.9% discussed it; and only 1.8% had patients ask about PGD. Most would refer for PGD for Huntington’s disease (HD) and Tay-Sachs, fewer for Cystic Fibrosis (CF), and fewer still for autism, Alzheimer’s (AD), or gender selection for family balancing; in each of these cases, psychiatrists > neurologists. Providers who’d refer for PGD for HD, CF, or gender selection differed from others in proportions of patients with insurance, were more likely to have undergone a GT themselves, and be concerned about discrimination. Conclusions These data, the first to examine how neurologists and psychiatrists view PGD, suggest they don’t feel comfortable discussing PGD, but have strong views about its use. Potential PGD use is associated with concerns about discrimination, and less experience with GT. These data highlight needs for enhancing education about these technologies among various providers. PMID:25098029

  2. 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

  3. 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

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

    SciTech Connect

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

    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.

  5. Addressing the idiosyncratic needs of Orthodox Jewish couples requesting sex selection by preimplantation genetic diagnosis (PGD).

    PubMed

    Grazi, Richard V; Wolowelsky, Joel B

    2006-01-01

    We report here on ethical considerations addressing the idiosyncratic needs of two Orthodox Jewish couples requesting sex selection through PGD. The patients' considerations stem from generally healthy concerns, are not based on any gender biases and have little chance of having any major societal impact, given the idiosyncratic nature of the situation. Halakhah, the legal and ethical system of rabbinic Orthodox Judaism, generally opposes sex selection through PGD for nonmedical reasons, but would approve the procedure in these cases. Meeting these needs within the context of the doctor-patient relationship necessitates reconsidering to some extent the ASRM Ethics Committee guidelines. PMID:17136601

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

    Microsoft Academic Search

    Y. Verlinsky; C. Strom; S. Rechitsky

    1994-01-01

    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

  7. Addressing the idiosyncratic needs of Orthodox Jewish couples requesting sex selection by preimplantation genetic diagnosis (PGD)

    Microsoft Academic Search

    Richard V. Grazi; Joel B. Wolowelsky

    2006-01-01

    We report here on ethical considerations addressing the idiosyncratic needs of two Orthodox Jewish couples requesting sex\\u000a selection through PGD. The patients’ considerations stem from generally healthy concerns, are not based on any gender biases\\u000a and have little chance of having any major societal impact, given the idiosyncratic nature of the situation. Halakhah, the\\u000a legal and ethical system of rabbinic

  8. Reprogenetics: Preimplantational genetics diagnosis

    PubMed Central

    Coco, Roberto

    2014-01-01

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

  9. The Ethics of Preimplantation Genetic Diagnosis

    NSDL National Science Digital Library

    2012-03-22

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

  10. [Examples of preimplantation genetic diagnosis versus prenatal diagnosis in carriers of genetic abnormalities: advantages and disadvantages].

    PubMed

    Snel, B J; Ypma, T D

    2008-03-29

    Preimplantation genetic diagnosis (PGD) is a method for identifying genetic abnormalities in embryos obtained via in-vitro fertilisation before their implantation. There are many indications for PGD, which offers an alternative to prenatal diagnosis, although each modality has its advantages and drawbacks. In three female patients there were clear indications for PGD: carriage of the gene for myotubular myopathy, a balanced complex chromosomal translocation, and a Robertsonian translocation in the male partner, respectively. The first patient eventually abandoned PGD and chose prenatal diagnosis. She had a total of three abortions. A twin pregnancy with a so-called foetal reduction resulted in the birth of a genetically normal child. The second patient had one spontaneous abortion and subsequently underwent two PGD cycles, resulting in an uncomplicated pregnancy and the delivery of a genetically normal child. The third patient had one genetically normal child and six spontaneous abortions. She then underwent the PGD procedure successfully and is expecting twins; the pregnancy has been uncomplicated. During preconception counselling of couples at high genetic risk, physicians should be aware of PGD as an alternative to prenatal diagnosis. PMID:18461896

  11. Analysis of Sex Chromosomes in Preimplantation Genetic Diagnosis for X-Chromosome-Linked Disorders

    Microsoft Academic Search

    Harumi Kubo; Yutaka Sasabe; Takayo Nishimura

    2002-01-01

    Preimplantation genetic diagnosis (PGD) is diagnostic tool to avoid inheritance of genetic disease by transferring unaffected embryos. Recently, PCR and FISH have been mainly applied to the diagnosis of single gene disorders and chromosomal abnormalities, respectively. Since with PGD, only a few cells are available for genetic tests, both gene and chromosomes analysis have to be obtained from the same,

  12. Preimplantation genetic diagnosis: does age of onset matter (anymore)?

    Microsoft Academic Search

    Timothy Krahn

    2009-01-01

    The identification and avoidance of disease susceptibility in embryos is the most common goal of preimplantation genetic diagnosis\\u000a (PGD). Most jurisdictions that accept but regulate the availability of PGD restrict it to what are characterized as ‘serious’\\u000a conditions. Line-drawing around seriousness is not determined solely by the identification of a genetic mutation. Other factors\\u000a seen to be relevant include: impact

  13. Views of internists towards uses of PGD

    PubMed Central

    Chung, Wendy; Marder, Karen; Shanmugham, Anita; Chin, Lisa J.; Stark, Meredith; Leu, Cheng-Shiun; Appelbaum, Paul S.

    2012-01-01

    Preimplantation genetic diagnosis (PGD) is increasingly available, but how physicians view it is unclear. Internists are gatekeepers and sources of information, often treating disorders for which PGD is possible. This quantitative study surveyed 220 US internists, who were found to be divided. Many would recommend PGD for cystic fibrosis (CF; 33.7%), breast cancer (BRCA; 23.4%), familial adenomatous polyposis (FAP; 20.6%) and familial hypertrophic cardiomyopathy (19.9%), but few for social sex selection (5.2%); however, in each case, >50% were unsure. Of those surveyed, 4.9% have suggested PGD to patients. Only 7.1% felt qualified to answer patient questions about it. Internists who would refer for PGD had completed medical training less recently and, for CF, were more likely to have privately insured patients (P < 0.033) and patients who reported genetic discrimination (P < 0.013). Physicians more likely to refer for BRCA and FAP were less likely to have patients ask about genetic testing. This study suggests that internists often feel they have insufficient knowledge about it and may refer for it based on limited understanding. They view possible uses of PGD differently, partly reflecting varying ages of onset and disease treatability. These data have critical implications for training, research and practice. PMID:23276655

  14. [Genetic diagnosis of IVF embryos: preliminary results from 'preimplantation genetic diagnoses' in the Netherlands].

    PubMed

    de Die-Smulders, C E; Geraedts, J P; Dreesen, J C; Coonen, E; Land, J A

    1998-11-01

    Preimplantation genetic diagnosis (PGD) is a very early form of genetic testing. It involves testing one or two cells taken from a recent embryo of eight cells produced by in vitro fertilization, and selective transfer of genetically normal embryos. So far in the Academic Hospital Maastricht, the Netherlands, 20 couples have undergone PGD, resulting in 6 ongoing pregnancies (one twin pregnancy). In three women the indications for PGD were: cystic fibrosis, sex-linked Pelizaeus-Merzbacher disease and chromosomal translocation, respectively. In the Netherlands PGD is only allowed if there is a high risk of a serious genetic disease. PGD can be carried out in Maastricht for: cystic fibrosis, sex-linked diseases, chromosomal abnormalities, fragile X syndrome, spinal muscular atrophy and myotonic dystrophy. The advantage of PGD is that it excludes the necessity of a therapeutic abortion. Disadvantages ages are the requirement of in vitro fertilization, which has only a 15-20% pregnancy rate, and the experimental nature of the PGD procedure. To date, about 200 children have been born worldwide following PGD. PMID:10028321

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

    PubMed

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

    2014-06-01

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

  16. Double locus analysis of chromosome 21 for preimplantation genetic diagnosis of aneuploidy

    Microsoft Academic Search

    M. C. Magli; M. Sandalinas; T. Escudero; L. Morrison; A. P. Ferraretti; L. Gianaroli

    2001-01-01

    Preimplantation genetic diagnosis (PGD) of numerical chromosome abnormalities significantly reduces spontaneous abortions and may increase pregnancy rates in women of advanced maternal age undergoing in vitro fertilization. However, the technique has an error rate of around 10% and trisomy 21 conceptions have occurred after PGD. To further reduce the risk of transferring trisomy 21 embryos to the patient, we designed

  17. Preimplantation genetic diagnosis in Saudi Arabia.

    PubMed

    Abotalib, Zeinab

    2013-01-01

    Preimplantation genetic diagnosis (PGD) testing is the practice of obtaining a cellular biopsy sample from a developing human oocyte or embryo, acquired via a cycle of in vitro fertilization (IVF); evaluating the genetic composition of this sample; and using this information to determine which embryos will be optimal for subsequent uterine transfer. PGD has become an increasingly useful adjunct to IVF procedures. The ability to provide couples who are known carriers of genetic abnormalities the opportunity to deliver healthy babies has opened a new frontier in reproductive medicine. The purpose of the PGD is enables us to choose which embryos will be implanted into the mother. In the present study 137 families who had undergone IVF at Habib Medical Centre, were enrolled for the PGD analysis. The couple visited the clinic for the sex selection, recurrent fetal loss and with the recurrent IVF failure. 802 embryos were tested by the biopsy method and 512 are found to be normal and 290 were abnormal embryos. In this study only 24% of the embryos were transferred and the remaining was not transferred because of the abnormalities or undesired sex of the embryos. The structural and numerical abnormalities were found to be 16.8%. PMID:23750087

  18. Preimplantation genetic diagnosis in Saudi Arabia

    PubMed Central

    Abotalib, Zeinab

    2013-01-01

    Preimplantation genetic diagnosis (PGD) testing is the practice of obtaining a cellular biopsy sample from a developing human oocyte or embryo, acquired via a cycle of in vitro fertilization (IVF); evaluating the genetic composition of this sample; and using this information to determine which embryos will be optimal for subsequent uterine transfer. PGD has become an increasingly useful adjunct to IVF procedures. The ability to provide couples who are known carriers of genetic abnormalities the opportunity to deliver healthy babies has opened a new frontier in reproductive medicine. The purpose of the PGD is enables us to choose which embryos will be implanted into the mother. In the present study 137 families who had undergone IVF at Habib Medical Centre, were enrolled for the PGD analysis. The couple visited the clinic for the sex selection, recurrent fetal loss and with the recurrent IVF failure. 802 embryos were tested by the biopsy method and 512 are found to be normal and 290 were abnormal embryos. In this study only 24% of the embryos were transferred and the remaining was not transferred because of the abnormalities or undesired sex of the embryos. The structural and numerical abnormalities were found to be 16.8%. PMID:23750087

  19. Preimplantation genetic diagnosis: design or too much design

    PubMed Central

    Verpoest, W.

    2009-01-01

    Preimplantation genetic diagnosis (PGD) is a technique that was first applied in humans in 1990 (Handyside et al., 1990; Verlinsky et al., 1990). Thirty years on an estimated 15000 children have been conceived and born using PGD, a number dwarfed by the huge number of children already conceived via conventional in vitro fertilisation. In contrast to numerous reports on reproductive outcome in conventional IVF, data on reproductive outcome of PGD are scarse. There is ongoing debate about the diagnostic accuracy and clinical relevance of Preimplantation genetic screening for aneuploidy (PGS) (Shahine et al., 2006; Twisk et al., 2006), however well conducted prospective randomized studies are few. In this PhD summary, the author describes the reproductive results of a large PGD program and applies life table analysis with multiple regression analysis and comparative analysis where appropriate. Potential risks of PGD including misdiagnosis, perinatal mortality and monozygotic twinning rate are assessed. The aim is to provide both patients and physicians with adequate information on all reproductive aspects of PGD as a diagnostic and therapeutic tool. PMID:25489466

  20. Preimplantation genetic diagnosis as an alternative to amniocentesis and chorionic villus sampling: psychosocial and ethical aspects.

    PubMed

    Vergeer, M M; van Balen, F; Ketting, E

    1998-09-01

    Social and ethical considerations play an increasing role in decisions about the use of diagnostic technologies. In this article expert opinions of a medical-biological and a social-ethical panel on psychosocial, ethical and social aspects of preimplantation genetic diagnosis (PGD) are discussed. PGD is a new diagnostic technology for identifying chromosomal or single gene defects, which is now available as a medical treatment in several western countries. In contrast to traditional technologies like amniocentesis and chorionic villus sampling PGD offers the possibility for diagnosis before pregnancy. The panels expected PGD to be chosen only in serious situations. IVF was considered to be a barrier for PGD but less so in more serious situations. Destruction of pre-embryos was thought more acceptable than selective abortion, but only marginally. Finally a substantial decrease was expected in the acceptance of handicapped people in society as a consequence of the possibilities of technologies like PGD. Although PGD offers new possibilities for couples at risk of having a child with a genetic defect, it is important that couples are counseled in a way that emphasizes both the advantages and disadvantages of the technology. The general public should be informed about possibilities and impossibilities of preventive diagnosis and the right of future parents not to use genetic diagnosis. PMID:9832892

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

    PubMed

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

    2015-01-01

    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

  2. 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

  3. 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

  4. Gender eugenics? The ethics of PGD for intersex conditions.

    PubMed

    Sparrow, Robert

    2013-01-01

    This article discusses the ethics of the use of preimplantation genetic diagnosis (PGD) to prevent the birth of children with intersex conditions/disorders of sex development (DSDs), such as congenital adrenal hyperplasia (CAH) and androgen insensitivity syndrome (AIS). While pediatric surgeries performed on children with ambiguous genitalia have been the topic of intense bioethical controversy, there has been almost no discussion to date of the ethics of the use of PGD to reduce the prevalence of these conditions. I suggest that PGD for those conditions that involve serious medical risks for those born with them is morally permissible and that PGD for other "cosmetic" variations in sexual anatomy is more defensible than might first appear. However, importantly, the arguments that establish the latter claim have radical and disturbing implications for our attitude toward diversity more generally. PMID:24024804

  5. 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

  6. Medical and social perspectives of PGD for single gene disorders and human leukocyte antigen typing

    Microsoft Academic Search

    Semra Kahraman; Necati Findikli; Guvenc Karliklaya; Semra Sertyel; Huseyin Karadayi; Yaman Saglam; Francesco Fiorentino

    2007-01-01

    Preimplantation genetic diagnosis (PGD) for single gene disorders combined with human leukocyte antigen (HLA) typing has recently emerged as a therapeutic tool. For couples who are at risk of passing on a genetic disease to their offspring, preimplantation embryos can be selected according to their genetic status as well as a possible HLA matching with the affected sibling. Stem cells

  7. First successful application of preimplantation genetic diagnosis and haplotyping for congenital hyperinsulinism

    Microsoft Academic Search

    Wafa Qubbaj; Abdulrahman Al-Swaid; Saad Al-Hassan; Khalid Awartani; Hesham Deek; Serdar Coskun

    2011-01-01

    Congenital hyperinsulinism is the most common cause of persistent hypoglycaemia in infancy. Early surgical intervention is usually required to prevent brain damage. The prevention of the transmission to the offspring is important in families carrying the mutated gene. Preimplantation genetic diagnosis (PGD) is an early genetic testing procedure for couples at risk of transmitting inherited diseases. A 36-year-old Saudi woman

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

    Microsoft Academic Search

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

    2009-01-01

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

  9. Preimplantation genetic diagnosis of Marfan syndrome with the use of fluorescent polymerase chain reaction and the Automated Laser Fluorescence DNA Sequencer ? ? Automated Laser Fluorescence DNA Sequencer, Pharmacia Biotech

    Microsoft Academic Search

    Karen Sermon; Willy Lissens; Ludwine Messiaen; Maryse Bonduelle; Mark Vandervorst; André Van Steirteghem; Inge Liebaers

    1999-01-01

    Objective: To develop and apply clinical preimplantation genetic diagnosis (PGD) for Marfan syndrome.Design: Case report.Setting: Centers for medical genetics and reproductive medicine in university hospitals.Patient(s): One couple in which the husband was affected with Marfan syndrome.Intervention(s): The couple underwent three intracytoplasmic sperm injection cycles.Main Outcome Measure(s): The correct diagnosis was obtained for embryos in three PGD cycles.Result(s): Although all the

  10. 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

  11. [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

  12. Choosing disability: preimplantation genetic diagnosis and negative enhancement.

    PubMed

    Karpin, Isabel

    2007-08-01

    This article examines the unusual circumstance of what the author has tentatively termed "negative enhancement". This term is used to describe those instances where individuals seek to use preimplantation genetic diagnosis (PGD) to achieve outcomes that, commonly, are socially not preferred. In a recent survey by the Genetics and Public Policy Centre, it was found that 3% of IVF-PGD clinics in the United States reported having provided PGD to couples who seek to select an embryo for the presence of a particular disease or disability, such as deafness, in order that the child share the characteristic with the parents. The idea of "negative enhancement" is, therefore, both a paradox and a useful means to describe the hidden assumptions behind claims that enhancement technologies can only lead us in one direction -- towards a race of blond, blue-eyed, able-bodied, intellectually magnificent and athletically superior beings. In Australia there does appear to be a consensus that PGD should only be used to select against serious disability. This inevitably raises the question of how we define disability and who is best placed to make decisions about the kind of kin we want to create. PMID:17902492

  13. Preimplantation diagnosis of a lysosomal storage disorder by in situ enzymatic activity: ‘Proof of principle’ in acid sphingomyelinase-deficient mice

    Microsoft Academic Search

    A. Butler; S. C. Henderson; R. E. Gordon; A. Dagan; S. Gatt; E. H. Schuchman

    2005-01-01

    Summary  Genetic diagnosis of preimplantation embryos (PGD) can substantially reduce the chance that at-risk couples have children\\u000a afflicted with inherited diseases. However, PGD requires DNA,which is usually obtained from single cells following embryo\\u000a biopsy. In addition, PGD requires that the genetic defect(s) causing the disorder be known. We have therefore developed an\\u000a alternative to PGD, which we term preimplantation enzymatic diagnosis

  14. 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

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

    Microsoft Academic Search

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

    2010-01-01

    Childhood DNA testing, prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) are available for familial adenomatous polyposis (FAP). However, the use of PND and PGD is controversial. The purpose of this study was to investigate attitudes toward, and experiences with, childhood DNA testing, PND and PGD among members of families at high risk for FAP. In this nationwide, cross-sectional study,

  16. Birth of healthy female twins after preimplantation genetic diagnosis of cystic fibrosis combined with gender determination

    Microsoft Academic Search

    Pierre F. Ray; Nelly Frydman; Tania Attie ´; Samir Hamamah; Violaine Kerbrat; Gerard Tachdjian; Serge Romana; Michel Vekemans; Arnold Munnich

    2002-01-01

    Two healthy sisters with a familial history of mental retardation were referred to our centre for preimplantation genetic diagnosis (PGD). Their two brothers showed severe mental retardation. The molecular basis for their disorder could not be identified, but one of the sisters and the mother presented a highly skewed pattern of X-inactivation reinforcing the likelihood of an X-linked mode of

  17. A qualitative inquiry of the financial concerns of couples opting to use preimplantation genetic diagnosis to prevent the transmission of known genetic disorders.

    PubMed

    Drazba, Kathryn T; Kelley, Michele A; Hershberger, Patricia E

    2014-04-01

    Preimplantation genetic diagnosis (PGD) is an innovative prenatal testing option because the determination of whether a genetic disorder or chromosomal abnormality is evident occurs prior to pregnancy. However, PGD is not covered financially under the majority of private and public health insurance institutions in the United States, leaving couples to decide whether PGD is financially feasible. The aim of this qualitative study was to understand the role of finances in the decision-making process among couples who were actively considering PGD. In-depth, semi-structured interviews were completed with 18 genetic high-risk couples (36 individual partners). Grounded theory guided the analysis, whereby three themes emerged: 1) Cost is salient, 2) Emotions surrounding affordability, and 3) Financial burden and sacrifice. Ultimately, couples determined that the opportunity to avoid passing on a genetic disorder to a future child was paramount to the cost of PGD, but expressed financial concerns and recognized financial access as a major barrier to PGD utilization. PMID:23949612

  18. A Qualitative Inquiry of the Financial Concerns of Couples Opting to Use Preimplantation Genetic Diagnosis to Prevent the Transmission of Known Genetic Disorders

    PubMed Central

    Drazba, Kathryn T.; Kelley, Michele A.; Hershberger, Patricia E.

    2013-01-01

    Preimplantation genetic diagnosis (PGD) is an innovative prenatal testing option because the determination of whether a genetic disorder or chromosomal abnormality is evident occurs prior to pregnancy. However, PGD is not covered financially under the majority of private and public health insurance institutions in the United States, leaving couples to decide whether PGD is financially feasible. The aim of this qualitative study was to understand the role of finances in the decision-making process among couples who were actively considering PGD. In-depth, semi-structured interviews were completed with 18 genetic high-risk couples (36 individual partners). Grounded theory guided the analysis, whereby three themes emerged: 1) Cost is salient, 2) Emotions surrounding affordability, and 3) Financial burden and sacrifice. Ultimately, couples determined that the opportunity to avoid passing on a genetic disorder to a future child was paramount to the cost of PGD, but expressed financial concerns and recognized financial access as a major barrier to PGD utilization. PMID:23949612

  19. Chromosomal complement and clinical relevance of multinucleated embryos in PGD and PGS cycles.

    PubMed

    Yilmaz, Ahmet; Zhang, Li; Zhang, Xiao Yun; Son, Weon-Young; Holzer, Hananel; Ao, Asangla

    2014-03-01

    The objective of this retrospective study was to investigate the incidence and clinical implications of multinucleation in blastomeres biopsied from cleavage-stage embryos obtained from patients undergoing preimplantation genetic screening (PGS) for aneuploidies or preimplantation genetic diagnosis (PGD) for translocations or single-gene defects (SGD). A total of 3515 embryos were obtained from 306 couples in 380 PGD or PGS cycles. Incidence of multinucleation, chromosomal complement in multinucleated (MN) and sibling embryos and the characteristics of MN embryos resulting in healthy births were investigated. Of all cycles, 41.3% involved at least one MN embryo. There were more uniformly diploid than uniformly haploid nuclei (22.0% versus 7.9%, P<0.01). The most common form of abnormality was chaotic chromosomal complement (39.9%, 147/368). Transfer of embryos that had MN blastomeres free of the genetic abnormalities tested resulted in three healthy deliveries. It is concluded that, although the majority of MN blastomeres are chromosomally abnormal, healthy births are possible after transfer of embryos containing these blastomeres subjected to genetic analysis. As far as is known, this is the first report of healthy births after transfer of embryos with MN blastomeres tested for translocations or SGD in PGD cycles. Preimplantation genetic diagnosis (PGD) is an established method for selecting genetically healthy embryos for transfer. A blastomere sampled from the developing embryo is subjected to genetic analysis. Some of these blastomeres may contain multiple nuclei, complicating the genetic diagnosis. We investigated clinical implications of multinucleation in PGD cycles. Our results indicate that majority of the multinucleated blastomeres, and consequently embryos, are genetically abnormal. However, healthy births are possible after transfer of multinucleated embryos that are free of the genetic abnormalities screened. PMID:24447961

  20. Conceptualizing Couples’ Decision Making in PGD: Emerging Cognitive, Emotional, and Moral Dimensions

    PubMed Central

    Hershberger, Patricia E.; Pierce, Penny F.

    2009-01-01

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

  1. 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

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

    Microsoft Academic Search

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

    2003-01-01

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

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

    PubMed Central

    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

  4. 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

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

    PubMed Central

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

    2014-01-01

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

  6. Preimplantation genetic diagnosis for cystic fibrosis: the Montpellier center's 10-year experience.

    PubMed

    Girardet, A; Ishmukhametova, A; Willems, M; Coubes, C; Hamamah, S; Anahory, T; Des Georges, M; Claustres, M

    2015-02-01

    This study provides an overview of 10?years of experience of preimplantation genetic diagnosis (PGD) for cystic fibrosis (CF) in our center. Owing to the high allelic heterogeneity of CF transmembrane conductance regulator (CFTR) mutations in south of France, we have set up a powerful universal test based on haplotyping eight short tandem repeats (STR) markers together with the major mutation p.Phe508del. Of 142 couples requesting PGD for CF, 76 have been so far enrolled in the genetic work-up, and 53 had 114 PGD cycles performed. Twenty-nine cycles were canceled upon in vitro fertilization (IVF) treatment because of hyper- or hypostimulation. Of the remaining 85 cycles, a total of 493 embryos were biopsied and a genetic diagnosis was obtained in 463 (93.9%), of which 262 (without or with a single CF-causing mutation) were transferable. Twenty-eight clinical pregnancies were established, yielding a pregnancy rate per transfer of 30.8% in the group of seven couples with one member affected with CF, and 38.3% in the group of couples whose both members are carriers of a CF-causing mutation [including six couples with congenital bilateral absence of the vas deferens (CBAVD)]. So far, 25 children were born free of CF and no misdiagnosis was recorded. Our test is applicable to 98% of couples at risk of transmitting CF. PMID:24762087

  7. Non-invasive pre-implantation genetic diagnosis of X-linked disorders.

    PubMed

    Assou, Said; Aït-Ahmed, Ounissa; El Messaoudi, Safia; Thierry, Alain R; Hamamah, Samir

    2014-10-01

    Pre-implantation genetic diagnosis (PGD) is a powerful clinical tool to identify embryos with or at risk of specific genetic diseases before implantation in utero after in vitro fertilization (IVF). PGD is performed on embryo biopsies that are obtained by aspiration of one or two cells from pre-implantation embryos at day 3 or day 5/6 of culture. However this is a traumatic method that cannot be avoided because non-invasive procedures to assess the genetic status of pre-implantation embryos are not available yet. We hypothesize that cell-free nucleic acids, which are released by embryos in the culture medium during the IVF procedure, could be used for genetic screening. To test our hypothesis we will focus first on X-linked disorders because these single-gene diseases due to the presence of defective genes on the X chromosome are dominant in males. Therefore the objective here is to discriminate between female (XX) and male (XY) embryos by detecting Y chromosome-specific sequences in cell-free nucleic acids. Using culture medium from embryos we are able to discriminate between male and female embryos. This opens new avenues for the development of a non-invasive PGD method. PMID:25182520

  8. 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.

  9. The Decision-Making Process of Genetically At-Risk Couples Considering Preimplantation Genetic Diagnosis: Initial Findings from a Grounded Theory Study

    PubMed Central

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

    2012-01-01

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

  10. 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

    2014-04-28

    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

  11. 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

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

    Microsoft Academic Search

    RG Edwards

    2004-01-01

    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

  13. Abnormal DLK1/MEG3 imprinting correlates with decreased HERV-K methylation after assisted reproduction and preimplantation genetic diagnosis.

    PubMed

    Dimitriadou, Eftychia; Noutsopoulos, Dimitrios; Markopoulos, Georgios; Vlaikou, Angeliki-Maria; Mantziou, Stefania; Traeger-Synodinos, Joanne; Kanavakis, Emmanouel; Chrousos, George P; Tzavaras, Theodore; Syrrou, Maria

    2013-11-01

    Retrotransposons participate in cellular responses elicited by stress, and DNA methylation plays an important role in retrotransposon silencing and genomic imprinting during mammalian development. Assisted reproduction technologies (ARTs) may be associated with increased stress and risk of epigenetic changes in the conceptus. There are similarities in the nature and regulation of LTR retrotransposons and imprinted genes. Here, we investigated whether the methylation status of Human Endogenous Retroviruses (HERV)-K LTR retrotransposons and the imprinting signatures of the DLK1/MEG3. p57(KIP2) and IGF2/H19 gene loci are linked during early human embryogenesis by examining trophoblast samples from ART pregnancies and preimplantation genetic diagnosis (PGD) cases and matched naturally conceived controls. Methylation analysis revealed that HERV-Ks were totally methylated in the majority of controls while, in contrast, an altered pattern was detected in ART-PGD samples that were characterized by a hemi-methylated status. Importantly, DLK1/MEG3 demonstrated disturbed methylation in ART-PGD samples compared to controls and this was associated with altered HERV-K methylation. No differences were detected in p57(KIP2) and IGF2/H19 methylation patterns between ART-PGD and naturally conceived controls. Using bioinformatics, we found that while the genome surrounding the p57(KIP2) and IGF2/H19 genes differentially methylated regions had low coverage in transposable element (TE) sequences, the respective one of DLK1/MEG3 was characterized by an almost 2-fold higher coverage. Moreover, our analyses revealed the presence of KAP1-binding sites residing within retrotransposon sequences only in the DLK1/MEG3 locus. Our results demonstrate that altered HERV-K methylation in the ART-PGD conceptuses is correlated with abnormal imprinting of the DLK1/MEG3 locus and suggest that TEs may be affecting the establishment of genomic imprinting under stress conditions. PMID:23786541

  14. Medium-Based Noninvasive Preimplantation Genetic Diagnosis for Human ?-Thalassemias-SEA.

    PubMed

    Wu, Haitao; Ding, Chenhui; Shen, Xiaoting; Wang, Jing; Li, Rong; Cai, Bing; Xu, Yanwen; Zhong, Yiping; Zhou, Canquan

    2015-03-01

    To develop a noninvasive medium-based preimplantation genetic diagnosis (PGD) test for ?-thalassemias.The embryos of ?-thalassemia carriers undergoing in vitro fertilization (IVF) were cultured. Single cells were biopsied from blastomeres and subjected to fluorescent gap polymerase chain reaction (PCR) analysis; the spent culture media that contained embryo genomic DNA and corresponding blastocysts as verification were subjected to quantitative-PCR (Q-PCR) detection of ?-thalassemia. The diagnosis efficiency and allele dropout (ADO) ratio were calculated, and the cell-free DNA concentration was quantitatively assessed in the culture medium.The diagnosis efficiency of medium-based ?-thalassemias detection significantly increased compared with that of biopsy-based fluorescent gap PCR analysis (88.6% vs 82.1%, P?PGD. PMID:25816038

  15. Accreditation of the PGD laboratory.

    PubMed

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

    2010-04-01

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

  16. Validating a rapid, real-time, PCR-based direct mutation detection assay for preimplantation genetic diagnosis.

    PubMed

    Chen, Hsin-Fu; Chang, Shun-Ping; Wu, Sheng-Hai; Lin, Wen-Hsiang; Lee, Yi-Chung; Ni, Yen-Hsuan; Chen, Chi-An; Ma, Gwo-Chin; Ginsberg, Norman A; You, En-Min; Tsai, Feng-Po; Chen, Ming

    2014-09-15

    Although co-amplification of polymorphic microsatellite markers is the current gold standard for preimplantation genetic diagnosis (PGD) of single-gene disorders (SGD), this approach can be hampered by the lack of availability of informative markers. We recently (2011) devised a novel in-house assay for PGD of aromatic L-amino acid decarboxylase deficiency, based on an amplification refractory mutation system and quantitative PCR (ARMS-qPCR). The objective of the present study was to verify ARMS-qPCR in a cohort of 20 PGD cycles with a diverse group of SGDs (15 couples at risk for 10 SGDs). Day-3 cleavage-stage embryos were subjected to biopsy and genotyping, followed by fresh embryo transfer (FET). The diagnostic rate was 82.9%; unaffected live births were achieved in 9 of 20 FET cycles (45%), with only one false negative (among 54 transferred embryos). Overall, the ARMS-qPCR had frequent allele-dropout (ADO), rendering it inappropriate as the sole diagnostic method (despite a favorable live-birth rate). Regardless, it has the potential to complement the current gold-standard methodology, especially when trophectoderm biopsy becomes a preferred option and genotyping needs to be timely enough to enable FET. PMID:25034658

  17. Preimplantation genetic diagnosis and the 'new' eugenics

    Microsoft Academic Search

    D S King

    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

  18. DNA diagnosis of human genetic individuality

    Microsoft Academic Search

    S. D. J. Pena; V. F. Prado; J. T. Epplen

    1995-01-01

    DNA studies of the human genome have shown polymorphic variation at thousands of sites, defining an absolute genetic uniqueness for each individual. There are many circumstances in which it may be desirable to diagnose this molecular individuality, as for instance, in criminal investigations or paternity testing. Several techniques can be used for this DNA diagnosis and we can choose among

  19. Outcomes of preimplantation genetic diagnosis using either zona drilling with acidified Tyrode's solution or partial zona dissection

    PubMed Central

    Kim, Hyun Jung; Kim, Chung Hyon; Lee, Soo Min; Choe, Seung Ah; Lee, Joong Yeup; Jee, Byung Chul; Hwang, Doyeong

    2012-01-01

    Objective To review the outcomes of preimplantation genetic diagnosis (PGD) using zona drilling with acid Tyrode's solution (chemical zona pellucida drilling, chemical ZD) and those of partial zona dissection (PZD). Methods Clinical outcomes of seventy-one couples undergoing 85 PGD cycles from January 2005 to December 2010 were included. Blastocyst formation and the hatching rate, clinical pregnancy rate, ongoing pregnancy rate, implantation rate, and fetal gender ratio of the PZD and chemical ZD groups were compared. Results Application of PZD resulted in a significantly higher rate of clinical pregnancy (40.7% vs. 15.4%, p=0.022), ongoing pregnancy (35.6% vs. 11.5%, p=0.023), and implantation (18.1% vs. 5.7%, p=0.007) compared with chemical ZD. Among non-transferred embryos, the rate of blastocyst formation on day 5 (49.1% vs. 39.5%, p=0.016) and hatching on day 6 (47.2% vs. 26.5%, p<0.001) were also significantly higher in the PZD group. Conclusion The mechanical zona dissection method showed better outcomes than chemical ZD in terms of the blastocyst development and pregnancy rate. In this study, the fact that chemical ZD was conducted in different period from mechanical method should be considered in interpreting the result. PMID:23106043

  20. Preimplantation genetic diagnosis of inherited disease.

    PubMed

    Ao, A

    1996-12-01

    Research on diagnosis of inherited disease in human embryo before implantation was initiated to help those couples who would prefer to select embryos at this stage rather than during pregnancy. Following in vitro fertilization (IVF), one to two cells were removed from 3 day cleavage stage embryo and cells were analysed for genetic defects. Embryos diagnosed as unaffected were returned to the uterus and thus the resulting pregnancies were assured to be normal. First babies born after the preimplantation diagnosis were using DNA amplification of Y-linked sequences by PCR to avoid X-linked disease. Several pregnancies were obtained by identifying sex of embryos using dual fluorescent in situ hybridization (FISH) with fluorochrome labelled DNA sequences specific for X- and Y-chromosomes to interphase nuclei. Development of single cell PCR for single gene defects led to diagnose several genetic disorders. Preimplantation diagnosis was successfully achieved for predominant delta 508 deletion causing cystic fibrosis, and pregnancies were also diagnosed for Lesch-Nyhan syndrome, Tay-Sachs and Duchenne muscular dystrophy. PMID:9246906

  1. Studying potential donors’ views on embryonic stem cell therapies and preimplantation genetic diagnosis

    PubMed Central

    HAIMES, ERICA; LUCE, JACQUELYNE

    2008-01-01

    Embryo experimentation raises many ethical questions, but is established as acceptable practice in the UK under the Human Fertilisation and Embryology Act 1990. The development of preimplantation genetic diagnosis (PGD) and embryonic stem (ES) cell research is dependent on couples undergoing in vitro fertilization (IVF) donating for research embryos that are unused in, or unsuitable for, treatment. Rarely is the role of these donors acknowledged, let alone studied. One concern is whether couples feel an obligation to donate embryos because of their gratitude for the IVF treatment they have received. This article, based on an ongoing study investigating the similarities and differences between the views and values of those IVF couples who agree to donate embryos for research and those who refuse to donate embryos, explores the broader issues around embryonic research. Discussions such as this, embedded in a background of empirical research, will assist practitioners and policymakers in assessing the social and ethical contexts of this very important aspect of current and future scientific developments. PMID:16825107

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

    PubMed

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

    2014-06-01

    Preimplantation genetic diagnosis is a procedure that involves the removal of one or more nuclei from oocytes (a polar body) or embryos (blastomeres or trophectoderm cells) in order to test for problems in genome sequence or chromosomes of the embryo prior to implantation. It provides new hope of having unaffected children, as well as avoiding the necessity of terminating an affected pregnancy for genetic parents who carry an affected gene or have balanced chromosomal status. Polymerase chain reaction-based molecular techniques are the methods used to detect gene defects with a known sequence and X-linked diseases. The indication for using this approach has expanded for couples who are prevented from having babies because they carry a serious genetic disorder to couples with conditions that are not immediately life threatening, such as cancer predisposition genes and Huntington disease. In addition, fluorescent in situ hybridization (FISH) has been widely applied for the detection of chromosome abnormalities. FISH allows the evaluation of many chromosomes at the same time, up to 15 chromosome pairs in a single cell. Preimplantation genetic screening, defined as a test that screens for aneuploidy, has been most commonly used in situations of advanced maternal age, a history of recurrent miscarriage, a history of repeated implantation failure, or a severe male factor. Unfortunately, randomized controlled trials have as yet shown no benefit with respect to preimplantation genetic screening using cleavage stage biopsy, which is probably attributable to the high levels of mosaicism at early cleavage stages and the limitations of FISH. Recently, two main types of array-based technology combined with whole genome amplification have been developed for use in preimplantation genetic diagnosis; these are comparative genomic hybridization and single nucleotide polymorphism-based arrays. Both allow the analysis of all chromosomes, and the latter also allows the haplotype of the sample to be determined. The promising results of these two approaches will inspire further validation of these array platforms, even at the single-cell level. It remains to be decided which embryo stage is the best for biopsy. Moreover, if randomized controlled trials are confirmed to play a role in increasing delivery rates, this will be a major step forward for assisted reproductive technology patients around the world. PMID:25017257

  3. [Having a child and PND/PGD access in women with a BRCA1/2 mutation? Different approach whether ill or healthy].

    PubMed

    Pellegrini, Isabelle; Prodromou, Niki; Coupier, Isabelle; Huiart, Laetitia; Moretta, Jessica; Noguès, Catherine; Julian-Reynier, Claire

    2014-11-01

    Genetic tests in families with a mutation related to breast and ovarian cancers (BRCA1/2) are now offered to the persons before completion of their reproductive project. The aim of this qualitative study was to descriptively explore how the issues of reproduction are faced in women belonging to these families, and how the possible use of prenatal diagnostic (PND) and preimplantation genetic diagnosis (PGD) would be faced in a theoretical context. We conducted in-depth interviews, face to face, according to the so-called Grounded Theory approach. Twenty women with a BRCA genetic mutation participated in the study (age range: 31-57 years); 12 have had a breast and/or ovarian cancer. The knowledge of having the mutation did not modify the parental project; however prophylactic anexectomy was likely to alter it in some women. If the majority of women were in favor of PGD (n = 14), medical termination of pregnancy was a constraint towards the position in relation to PND. Besides ethical and moral arguments, the women's attitudes were constructed differently according to their own personal or familial experience of the disease. The women's perceptions of the cancer severity, risk and cure were organized according to this experience. PMID:25418592

  4. New Genetic Variants Improve Personalized Breast Cancer Diagnosis

    PubMed Central

    Liu, Jie; Page, David; Peissig, Peggy; McCarty, Catherine; Onitilo, Adedayo A.; Trentham-Dietz, Amy; Burnside, Elizabeth

    2014-01-01

    Recent large-scale genome-wide association 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 remains unknown. We conducted a case-control study and collected mammography features and 77 genetic variants which reflect the state of the art GWAS findings on breast cancer. A naïve Bayes model was developed on the mammography features and these genetic variants. We observed that the incorporation of the genetic variants significantly improved breast cancer diagnosis based on mammographic findings. PMID:25717406

  5. Lactose intolerance: diagnosis, genetic, and clinical factors.

    PubMed

    Mattar, Rejane; de Campos Mazo, Daniel Ferraz; Carrilho, Flair José

    2012-01-01

    Most people are born with the ability to digest lactose, the major carbohydrate in milk and the main source of nutrition until weaning. Approximately 75% of the world's population loses this ability at some point, while others can digest lactose into adulthood. This review discusses the lactase-persistence alleles that have arisen in different populations around the world, diagnosis of lactose intolerance, and its symptomatology and management. PMID:22826639

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

    Microsoft Academic Search

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

    1998-01-01

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

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

    PubMed Central

    Hepburn, E R

    1996-01-01

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

  8. Critical issues for dentistry: PGD program directors respond.

    PubMed

    Atchison, Kathryn A; Cheffetz, Susan E

    2002-06-01

    Discussion of critical issues facing postgraduate education in general dentistry (PGD) and dental education in general has been intense in the past decade. This study reports on critical issues raised by directors of PGD programs that may help direct future research and action within dental education and the larger profession. The analysis reports responses to an open-ended question sent to all U.S. PGD program directors regarding critical issues facing their training programs. Of 212 surveys, 169 program directors submitted written responses regarding critical issues. Twelve unique themes were identified: lack of postdoctoral applicants (two subthemes were high student debt and students' preference for private practice); student quality; professionalism and attitudes; number of postdoctoral positions; lack of funding; quality of facilities; special patient care; program curriculum; educator issues; mandatory or encouraged PGD year; value of dental program; and dentist shortage. Significant differences between AEGD and GPR directors were observed for two of the twelve areas: high student debt and value of dental program. The study provided insight into the thoughts of a large proportion of the U.S. PGD program directors "in the trenches." Some consideration of allowable expenses may be needed to align federal training support to best address program director needs. PMID:12117095

  9. My Funky Genetics: BRCA1\\/2 Mutation Carriers' Understanding of Genetic Inheritance and Reproductive Merger in the Context of New Reprogenetic Technologies

    Microsoft Academic Search

    Allison Werner-Lin; Lisa R. Rubin; Maya Doyle; Rikki Stern; Katie Savin; Karen Hurley; Michal Sagi

    2012-01-01

    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. Preimplantation genetic diagnosis (PGD) permits prospective parents to avoid the birth of a BRCA-mutation-positive child, introducing predictability into a process historically defined by chance. This investigation explored how BRCA1\\/2 mutation carriers understand genetic

  10. 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.

  11. Critical Issues for Dentistry: PGD Program Directors Respond.

    ERIC Educational Resources Information Center

    Atchison, Kathryn A.; Cheffetz, Susan E.

    2002-01-01

    Surveyed directors of programs in postgraduate education in general dentistry (PGD) about critical issues facing their programs. Identified 12 themes: lack of postdoctoral applicants; student quality; professionalism and attitudes; number of postdoctoral positions; lack of funding; quality of facilities; special patient care; program curriculum;…

  12. Chronic pancreatitis: diagnosis, classification, and new genetic developments.

    PubMed

    Etemad, B; Whitcomb, D C

    2001-02-01

    The utilization of recent advances in molecular and genomic technologies and progress in pancreatic imaging techniques provided remarkable insight into genetic, environmental, immunologic, and pathobiological factors leading to chronic pancreatitis. Translation of these advances into clinical practice demands a reassessment of current approaches to diagnosis, classification, and staging. We conclude that an adequate pancreatic biopsy must be the gold standard against which all diagnostic approaches are judged. Although computed tomography remains the initial test of choice for the diagnosis of chronic pancreatitis, the roles of endoscopic retrograde pancreatography, endoscopic ultrasonography, and magnetic resonance imaging are considered. Once chronic pancreatitis is diagnosed, proper classification becomes important. Major predisposing risk factors to chronic pancreatitis may be categorized as either (1) toxic-metabolic, (2) idiopathic, (3) genetic, (4) autoimmune, (5) recurrent and severe acute pancreatitis, or (6) obstructive (TIGAR-O system). After classification, staging of pancreatic function, injury, and fibrosis becomes the next major concern. Further research is needed to determine the clinical and natural history of chronic pancreatitis developing in the context of various risk factors. New methods are needed for early diagnosis of chronic pancreatitis, and new therapies are needed to determine whether interventions will delay or prevent the progression of the irreversible damage characterizing end-stage chronic pancreatitis. PMID:11179244

  13. The borderline diagnosis III: identifying endophenotypes for genetic studies.

    PubMed

    Siever, Larry J; Torgersen, Svenn; Gunderson, John G; Livesley, W John; Kendler, Kenneth S

    2002-06-15

    Although it is generally acknowledged that borderline personality disorder (BPD) has a complex, multifactorial etiology with interacting genetic and environmental substrates, the specific genetic underpinnings of this disorder have not been extensively investigated. Family aggregation studies suggest the heritability for BPD as a diagnosis, but the genetic basis for this disorder may be stronger for dimensions such as impulsivity/aggression and affective instability than for the diagnostic criteria itself. Family, adoptive, and twin studies also converge to support an underlying genetic component to the disorder. An endophenotypic approach to defining the genetics of this complex disorder may be called for. Twin studies in an epidemiologic, non-clinically ascertained sample using both diagnostic measures and laboratory measures that can be operationalized, including neuropsychologic, psychophysiologic, and operationalized behavioral tests, may be useful. Large-scale family studies of clinically ascertained samples with careful diagnostic demarcation and measurement of endophenotypes in probands and relatives may also prove to be a promising approach. The use of laboratory paradigms for measures of aggression and affective instability are discussed in the context of such endophenotypic approaches. PMID:12062879

  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 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

  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

    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

  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. [Molecular Tool, Inc., Baltimore, MD (United States)] [and others

    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. New canine models of copper toxicosis: diagnosis, treatment, and genetics.

    PubMed

    Fieten, Hille; Penning, Louis C; Leegwater, Peter A J; Rothuizen, Jan

    2014-05-01

    The One Health principle recognizes that human health, animal health, and environmental health are inextricably linked. An excellent example is the study of naturally occurring copper toxicosis in dogs to help understand human disorders of copper metabolism. Besides the Bedlington terrier, where copper toxicosis is caused by a mutation in the COMMD1 gene, more complex hereditary forms of copper-associated hepatitis were recognized recently in other dog breeds. The Labrador retriever is one such breed, where an interplay between genetic susceptibility and exposure to copper lead to clinical copper toxicosis. Purebred dog populations are ideal for gene mapping studies, and because genes involved in copper metabolism are highly conserved across species, newly identified gene mutations in the dog may help unravel the genetic complexity of different human forms of copper toxicosis. Furthermore, increasing knowledge with respect to diagnosis and treatment strategies will benefit both species. PMID:24758744

  18. Successful application of preimplantation genetic diagnosis for hypokalaemic periodic paralysis.

    PubMed

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

    2010-08-01

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

  19. Genetic markers for diagnosis and pathogenesis of Alzheimer's disease.

    PubMed

    Kim, Dong Hee; Yeo, Seung Hyeon; Park, Jeong-Min; Choi, Ji Ye; Lee, Tae-Hee; Park, Soon Yong; Ock, Mee Sun; Eo, Jungwoo; Kim, Heui-Soo; Cha, Hee-Jae

    2014-07-25

    Alzheimer's disease (AD) is the most common form of dementia in the elderly and represents an important and increasing clinical challenge in terms of diagnosis and treatment. Mutations in the genes encoding amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) are responsible for early-onset autosomal dominant AD. The ?4 allele of the apolipoprotein E (APOE) gene has been recognized as a major genetic risk factor for the more common, complex, late-onset AD. Fibrillar deposits by phosphorylated tau are also a key pathological feature of AD. The retromer complex also has been reported to late-onset AD. More recently, genome-wide association studies (GWASs) identified putative novel candidate genes associated with late-onset AD. Lastly, several studies showed that circulating microRNAs (miRNAs) in the cerebrospinal fluid (CSF) and blood serum of AD patients can be used as biomarkers in AD diagnosis. This review addresses the advances and challenges in determining genetic and diagnostic markers for complex AD pathogenesis. PMID:24838203

  20. Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management

    Microsoft Academic Search

    Henry T. Lynch; Jane F. Lynch; Patrick M. Lynch; Thomas Attard

    2008-01-01

    Hereditary forms of colorectal cancer, as is the case with virtually all forms of hereditary cancer, show extensive phenotypic\\u000a and genotypic heterogeneity, a phenomenon discussed throughout this special issue of Familial Cancer. Clearly, the family\\u000a physician, oncology specialist, genetic counselor, and cancer geneticist must know fully the complexity of hereditary cancer\\u000a syndromes, their differential diagnosis, in order to establish a

  1. Genetic diagnosis and prognosis of Alzheimer's disease: challenges and opportunities.

    PubMed

    Reitz, Christiane

    2015-03-01

    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 the diagnosis and prognosis of AD. PMID:25634383

  2. Accumulation of oocytes and/or embryos by vitrification: a new strategy for managing poor responder patients undergoing pre implantation diagnosis

    PubMed Central

    Chatziparasidou, Alexia; Nijs, Martine; Moisidou, Martha; Chara, Oraiopoulou; Ioakeimidou, Christina; Pappas, Christos; Christoforidis, Nicos

    2014-01-01

    Background: Low (or poor) responder patients are women who require large doses of stimulation medications and produce less than an optimal number of oocytes during IVF cycles. Low responder patients produce few oocytes and embryos, which significantly reduces their chances for success in a preimplantation genetic diagnosis (PGD) cycle. Accumulation of vitrified oocytes or embryos before the actual PGD cycle is a possible strategy that might increase patient’s chances for a healthy pregnancy. Aim of the study: This retrospective study evaluates the efficacy of a PGD program in low responder patients after repeated ovarian stimulation cycles with cumulative vitrification of oocytes and embryos. Methods: Over a period of 30 months, 13 patients entering the PGD program were identified as poor responders after their first ovarian stimulation. These patients started a PGD cycle for one of the following indications: history of recurrent implantation failure (n=1), cystic fibrosis (n=1), X-linked microtubular myopathy (n=1), recurrent miscarriages (n=5), Duchene muscular dystrophy (n=1), chromosomal translocation (n=1) and high sperm aneuploidy (n=1).  After multiple ovarian hormonal stimulations patients had either all mature oocytes (Group A; 3 patients) or all of their day 2 embryos vitrified (group B; 10 patients). Mean total number of oocyte collections per patient was 2.3 (range: 2 - 5 cycles). Results: In the actual PGD cycle, all vitrified oocytes from group A patients were warmed and underwent intra cytoplasmic sperm injection (ICSI) followed by culture up to day 3. For group B patients all vitrified day 2 embryos were warmed and cultured overnight. On day 3 of culture, all embryos from Group A and B had blastomere biopsy followed by genetic analysis. In group A, 20 embryos were found suitable for biopsy and genetic analysis; at least one healthy embryo was available for transfer for each patient.  For group B, 72 embryos in total were available for biopsy and PGD.  All patients, except one, had at least one healthy day 5 embryo for transfer (mean number of 2.1 embryos per transfer). Nine patients had a clinical pregnancy; 7 patients delivered a healthy baby. Conclusion: Low responder patients entering a PGD program might increase their chances for a healthy pregnancy by repeat ovarian stimulation in combination with cumulative oocyte or embryo vitrification. PMID:25110577

  3. The Decision-Making Process of Genetically At-Risk Couples Considering Preimplantation Genetic Diagnosis: Initial Findings from a Grounded Theory Study

    E-print Network

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

    2012-01-01

    Decision Making; Decision Theory; Family Planning; In VitroDecision-Making Process of Genetically At-Risk Couples Considering Preimplantation Genetic Diagnosis: Initial Findings from a Grounded Theory

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

    Microsoft Academic Search

    RG Edwards

    2003-01-01

    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

  5. ‘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

  6. Improving family communication after a new genetic diagnosis: a randomised controlled trial of a genetic counselling intervention

    PubMed Central

    2014-01-01

    Background Genetic information given to an individual newly diagnosed with a genetic condition is likely to have important health implications for other family members. The task of communicating with these relatives commonly falls to the newly diagnosed person. Talking to relatives about genetic information can be challenging and is influenced by many factors including family dynamics. Research shows that many relatives remain unaware of relevant genetic information and the possible impact on their own health. This study aims to evaluate whether a specific genetic counselling intervention for people newly diagnosed with a genetic condition, implemented over the telephone on a number of occasions, could increase the number of at-risk relatives who make contact with genetics services after a new genetic diagnosis within a family. Methods This is a prospective, multi-centre randomised controlled trial being conducted at genetics clinics at five public hospitals in Victoria, Australia. A complex genetic counselling intervention has been developed specifically for this trial. Probands (the first person in a family to present with a diagnosis of a genetic condition) are being recruited and randomised into one of two arms – the telephone genetic counselling intervention arm and the control arm receiving usual care. The number of at-risk relatives for each proband will be estimated from a family pedigree collected at the time of diagnosis. The primary outcome will be measured by comparing the proportion of at-risk relatives in each arm of the trial who make subsequent contact with genetics services. Discussion This study, the first randomised controlled trial of a complex genetic counselling intervention to enhance family communication, will provide evidence about how best to assist probands to communicate important new genetic information to their at-risk relatives. This will inform genetic counselling practice in the context of future genomic testing. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ANZCTRN12608000642381. PMID:24628824

  7. Application of genetic algorithms to fault diagnosis in nuclear power plants

    Microsoft Academic Search

    Zhou Yangping; Zhao Bingquan; Wu DongXin

    2000-01-01

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

  8. Study on Power Transformer Fault Diagnosis Based on Niche Genetic Algorithm

    Microsoft Academic Search

    Jiyin Zhao; Ruirui Zheng; Haihong Dong

    2009-01-01

    Power transformer fault diagnosis is the key technology of electric power system. Niche genetic algorithm (NGA) was introduced to optimize adaptive-learning-rate-momentum back propagation (BP) network. NGA-BP model was established and applied to power transformer fault diagnosis. Compared with BP network, NGA-BP network has a better performance on convergent speed and stability. The experimental results demonstrate that fault diagnosis precision of

  9. Research on Fault Diagnosis of Mixed-Signal Circuits Based on Genetic Algorithms

    Microsoft Academic Search

    Shangcong Feng; Xiaofeng Wang

    2012-01-01

    As the fault modes of mixed-signal circuits growing, aiming at the features for its signal are both analog and digital amount, the paper analyzed that the fault diagnosis program of mixed-signal circuits with genetic algorithms by using SABER simulation method to inject faults and data collection based on a brief discussion of basic principles and operation of genetic algorithms, focused

  10. A Case Study on Medical Diagnosis of Cardiovascular Diseases Using a Genetic Algorithm

    E-print Network

    Granada, Universidad de

    A Case Study on Medical Diagnosis of Cardiovascular Diseases Using a Genetic Algorithm for Tuning cardiovascular diseases. Specifically, we use a methodology in which the linguistic labels of the classifier, Interval-Valued Fuzzy Sets, Tuning, Ignorance Functions, Genetic Fuzzy Systems, Cardiovascular Disease. I

  11. 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

  12. 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

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

    PubMed

    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 and 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

  14. 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

  15. Targeted massively parallel sequencing provides comprehensive genetic diagnosis for patients with disorders of sex development

    PubMed Central

    Arboleda, VA; Lee, H; Sánchez, FJ; Délot, EC; Sandberg, DE; Grody, WW; Nelson, SF; Vilain, E

    2013-01-01

    Disorders of sex development (DSD) are rare disorders in which there is discordance between chromosomal, gonadal, and phenotypic sex. Only a minority of patients clinically diagnosed with DSD obtains a molecular diagnosis, leaving a large gap in our understanding of the prevalence, management, and outcomes in affected patients. We created a novel DSD-genetic diagnostic tool, in which sex development genes are captured using RNA probes and undergo massively parallel sequencing. In the pilot group of 14 patients, we determined sex chromosome dosage, copy number variation, and gene mutations. In the patients with a known genetic diagnosis (obtained either on a clinical or research basis), this test identified the molecular cause in 100% (7/7) of patients. In patients in whom no molecular diagnosis had been made, this tool identified a genetic diagnosis in two of seven patients. Targeted sequencing of genes representing a specific spectrum of disorders can result in a higher rate of genetic diagnoses than current diagnostic approaches. Our DSD diagnostic tool provides for first time, in a single blood test, a comprehensive genetic diagnosis in patients presenting with a wide range of urogenital anomalies. PMID:22435390

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  18. The Role of Molecular Genetic Analysis in the Diagnosis of Primary Ciliary Dyskinesia

    PubMed Central

    Kim, Raymond H.; A. Hall, David; Cutz, Ernest; Knowles, Michael R.; Nelligan, Kathleen A.; Nykamp, Keith; Zariwala, Maimoona A.

    2014-01-01

    Rationale: Primary ciliary dyskinesia (PCD) is an autosomal recessive genetic disorder of motile cilia. The diagnosis of PCD has previously relied on ciliary analysis with transmission electron microscopy or video microscopy. However, patients with PCD may have normal ultrastructural appearance, and ciliary analysis has limited accessibility. Alternatively, PCD can be diagnosed by demonstrating biallelic mutations in known PCD genes. Genetic testing is emerging as a diagnostic tool to complement ciliary analysis where interpretation and access may delay diagnosis. Objectives: To determine the diagnostic yield of genetic testing of patients with a confirmed or suspected diagnosis of PCD in a multiethnic urban center. Methods: Twenty-eight individuals with confirmed PCD on transmission electron microscopy of ciliary ultrastructure and 24 individuals with a probable diagnosis of PCD based on a classical PCD phenotype and low nasal nitric oxide had molecular analysis of 12 genes associated with PCD. Results: Of 49 subjects who underwent ciliary biopsy, 28 (57%) were diagnosed with PCD through an ultrastructural defect. Of the 52 individuals who underwent molecular genetic analysis, 22 (42%) individuals had two mutations in known PCD genes. Twenty-four previously unreported mutations in known PCD genes were observed. Combining both diagnostic modalities of biopsy and molecular genetics, the diagnostic yield increased to 69% compared with 57% based on biopsy alone. Conclusions: The diagnosis of PCD is challenging and has traditionally relied on ciliary biopsy, which is unreliable as the sole criterion for a definitive diagnosis. Molecular genetic analysis can be used as a complementary test to increase the diagnostic yield. PMID:24498942

  19. Recent advances in the diagnosis, genetics and treatment of restless legs syndrome

    Microsoft Academic Search

    Claudia Trenkwalder; Birgit Högl; Juliane Winkelmann

    2009-01-01

    \\u000a Abstract\\u000a   Knowledge of restless legs syndrome (RLS) has greatly increased in recent years due to the many advances that have been made\\u000a in diagnosis, management and genetics. Tools have been developed that facilitate the diagnosis and treatment of RLS, in particular\\u000a the essential diagnostic criteria for RLS have been refined, severity scales (IRLS, RLS-6, JHSS) have been developed, as have

  20. Modeling the genetic and environmental association between peer group deviance and cannabis use in male twins

    PubMed Central

    Gillespie, Nathan A; Neale, Michael C; Jacobson, Kristen; Kendler, Kenneth S

    2009-01-01

    Background Peer group deviance (PGD) is strongly linked to liability to drug use including cannabis. Our aim was to model the genetic and environmental association, including direction of causation, between PGD and cannabis use (CU). Method Results were based on 1753 adult males from the Mid-Atlantic Twin Registry with complete CU and PGD data measured retrospectively at three time intervals between 15 and 25 years using a life-history calendar. Results At all ages, multivariate modeling showed that familial aggregation in PGD was explained by a combination of additive genetic and shared environmental effects, Moreover the significant PGD-CU association was best explained by a CU to PGD causal model in which large portions of the additive genetic (50% to 78%) and shared environmental variance (25% to 73%) in PGD were explained by CU. Conclusions Until recently PGD was assumed to be an environmental, upstream risk factor for CU. Our data are not consistent with this hypothesis. Rather, they suggest that the liability to affiliate with deviant peers is better explained by a combination of genetic and environmental factors that are indexed by CU which sits as a “risk indicator” in the causal pathway between genetic and environmental risks and the expression of PGD. This is consistent with a process of social selection by which the genetic and environmental risks in CU largely drive the propensity to affiliate with deviant peers. PMID:19207350

  1. Ethical and legal aspects of noninvasive prenatal genetic diagnosis.

    PubMed

    Dickens, Bernard M

    2014-02-01

    The new technology that will allow genetic testing of a fetus within the first trimester of pregnancy by isolating cell-free fetal DNA (cffDNA) in the mother's blood raises a range of ethical and legal issues. Considered noninvasive, this test is safe and reliable, and may avoid alternative genetic testing by amniocentesis or chorionic villus sampling, which risks causing spontaneous abortion. Ethical and legal issues of cffDNA testing will become more acute if testing expands to fetal whole-genome sequencing. Critical issues include the state of the science or diagnostic art; the appropriateness of offering the test; the implications of denying the test when it is available and appropriate; disclosure and counseling following test results; and management of patients' choices on acquiring test results. A challenge will be providing patients with appropriate counseling based on up-to-date genetic knowledge, and accommodating informed patients' legal choices. PMID:24299974

  2. 6-phosphogluconate dehydrogenase activity variants in Musca domestica L.: A further allele at the Pgd locus as proved by densitometric assay

    Microsoft Academic Search

    G. Gasperi; A. Malacrida; R. Milani

    1983-01-01

    A new electrophoretic variant of 6-phosphogluconate dehydrogenase (6PGD) has been detected in flies of a laboratoryMusca domestica strain. This variant is to be added to the two already described, PGD-A and PGD-B, identified by a fast-weak and a slow-thick\\u000a electrophoretic band, respectively. The new variant, PGD-C, has the same mobility as PGD-A but provides a more intensely stained\\u000a band; therefore

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

    PubMed

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

    2006-05-01

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

  4. Genetic Approaches for the Diagnosis and Treatment of Congenital Tooth Agenesis

    E-print Network

    Bonds, John Carless

    2014-08-06

    patients would be prevention based on knowledge about the genetic origin of the disorder. Understanding the molecular genetics will most likely play an important role in the diagnosis, prognosis, and treatment of dental disorders such as caries... epithelial signals around embryonic day E11.5, after the formation of the dental lamina around the dental placode stage. Mechanical compaction of mesenchymal cells may be the driving force for the initiation of Pax9 expression (Mammoto and Ingber, 2010...

  5. 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

  6. 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

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

    Microsoft Academic Search

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

    1999-01-01

    This study investigates the degree to which the performance of Bayesian belief networks (BBNs), for computer-assisted diagnosis of breast cancer, can be improved by optimizing their input feature sets using a genetic algorithm (GA). 421 cases (all women) were used in this study, of which 92 were positive for breast cancer. Each case contained both non-image information and image information

  8. Application of the polymerase chain reaction to the diagnosis of human genetic disease

    Microsoft Academic Search

    Jochen Reiss; David N. Cooper

    1990-01-01

    In vitro DNA amplification by means of the polymerase chain reaction is currently revolutionizing human molecular genetics. Since its inception in 1985, a wide variety of different methods and their applications in the diagnosis of disease have been described. This review is intended to serve as a brief guide to current and emerging possibilities in this rapidly expanding field.

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

    E-print Network

    Fernandez, Thomas

    Genetic programming as a method to develop powerful predictive models for clinical diagnosis Ivar models in an optimal way. In this paper we discuss as an example the diagnostic prediction of pul- monary, Prognosis, Logistic Re- gression, Pulmonary Embolism 1. INTRODUCTION The use of predictive models

  10. 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

  11. Aortopathies: etiologies, genetics, differential diagnosis, prognosis and management.

    PubMed

    Paterick, Timothy E; Humphries, Julie A; Ammar, Khawaja Afzal; Jan, M Fuad; Loberg, Rachel; Bush, Michelle; Khandheria, Bijoy K; Tajik, A Jamil

    2013-08-01

    Aortic root and ascending aortic dilatation are indicators associated with risk of aortic dissection, which varies according to underlying etiologic associations, indexed aortic root size, and rate of progression. Typical aortic involvement is most commonly seen in syndromic cases for which there is increasing evidence that aortic aneurysm represents a spectrum of familial inheritance associated with variable genetic penetrance and phenotypic expression. Aortic root and ascending aortic dimensions should be measured routinely with echocardiography. Pharmacologic therapy may reduce the rate of progression. Timing of surgical intervention is guided by indexed aortic size and rate of change of aortic root and ascending aorta dimensions. Lifelong surveillance is recommended. PMID:23800581

  12. 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

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

    NSDL National Science Digital Library

    Libin Wang (University of Miami)

    2010-04-20

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

  14. Genetic diagnosis strategy of hereditary non-polyposis colorectal cancer

    PubMed Central

    Sheng, Jian-Qiu; Zhang, Hong; Ji, Min; Fu, Lei; Mu, Hong; Zhang, Ming-Zhi; Huang, Ji-Sheng; Han, Min; Li, Ai-Qin; Wei, Zhi; Sun, Zi-Qin; Wu, Zi-Tao; Xia, Chang-Hong; Li, Shi-Rong

    2009-01-01

    AIM: To study the characteristics of mismatch repair gene mutation of Chinese hereditary non-polyposis colorectal cancer (HNPCC) and hMLH1 gene promoter methylation, and to improve the screening strategy and explore the pertinent test methods. METHODS: A systematic analysis of 30 probands from HNPCC families in the north of China was performed by immunohistochemistry, microsatellite instability (MSI), gene mutation and methylation detection. RESULTS: High frequency microsatellite instability occurred in 25 probands (83.3%) of HNPCC family. Loss of hMLH1 and hMSH2 protein expression accounted for 88% of all microsatellite instability. Pathogenic mutation occurred in 14 samples and 3 novel mutational sites were discovered. Deletion of exons 1-6, 1-7 and 8 of hMSH2 was detected in 3 samples and no large fragment deletion was found in hMLH1. Of the 30 probands, hMLH1 gene promoter methylation occurred in 3 probands. The rate of gene micromutation detection combined with large fragment deletion detection was 46.7%-56.7%. The rate of the two methods in combination with methylation detection was 63.3%. CONCLUSION: Scientific and rational detection strategy can improve the detection rate of HNPCC. Based on traditional molecular genetics and combined with epigenetics, multiple detection methods can accurately diagnose HNPCC. PMID:19248199

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

    PubMed

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

    2014-10-01

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

  16. 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?

  17. 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.

  18. Prenatal Diagnosis of ?-Thalassemias and Hemoglobinopathies.

    PubMed Central

    Rosatelli, Maria Cristina; Saba, Luisella

    2009-01-01

    Prenatal diagnosis of ?-thalassemia was accomplished for the first time in the 1970s by globin chain synthesis analysis on fetal blood obtained by placental aspiration at 18–22 weeks gestation. Since then, the molecular definition of the ?-globin gene pathology, the development of procedures of DNA analysis, and the introduction of chorionic villous sampling have dramatically improved prenatal diagnosis of this disease and of related disorders. Much information is now available about the molecular mechanisms of the diseases and the molecular testing is widespread. As prenatal diagnosis has to provide an accurate, safe and early result, an efficient screening of the population and a rapid molecular characterization of the couple at risk, are necessary prerequisites. In the last decades earlier and less invasive approaches for prenatal diagnosis were developed. A overview of the most promising procedure will be done. Moreover, in order to reduce the choice of interrupting the pregnancy in case of affected fetus, Preimplantation or Preconceptional Genetic Diagnosis (PGD) has been setting up for several diseases including thalassemias PMID:21415992

  19. Prenatal Diagnosis of ?-Thalassemias and Hemoglobinopathies.

    PubMed

    Rosatelli, Maria Cristina; Saba, Luisella

    2009-01-01

    Prenatal diagnosis of ?-thalassemia was accomplished for the first time in the 1970s by globin chain synthesis analysis on fetal blood obtained by placental aspiration at 18-22 weeks gestation. Since then, the molecular definition of the ?-globin gene pathology, the development of procedures of DNA analysis, and the introduction of chorionic villous sampling have dramatically improved prenatal diagnosis of this disease and of related disorders. Much information is now available about the molecular mechanisms of the diseases and the molecular testing is widespread. As prenatal diagnosis has to provide an accurate, safe and early result, an efficient screening of the population and a rapid molecular characterization of the couple at risk, are necessary prerequisites. In the last decades earlier and less invasive approaches for prenatal diagnosis were developed. A overview of the most promising procedure will be done. Moreover, in order to reduce the choice of interrupting the pregnancy in case of affected fetus, Preimplantation or Preconceptional Genetic Diagnosis (PGD) has been setting up for several diseases including thalassemias. PMID:21415992

  20. New Advances of Preimplantation and Prenatal Genetic Screening and Noninvasive Testing as a Potential Predictor of Health Status of Babies

    PubMed Central

    2014-01-01

    The current morphologically based selection of human embryos for transfer cannot detect chromosome aneuploidies. So far, only biopsy techniques have been able to screen for chromosomal aneuploidies in the in vitro fertilization (IVF) embryos. Preimplantation genetic diagnosis (PGD) or screening (PGS) involves the biopsy of oocyte polar bodies or embryonic cells and has become a routine clinical procedure in many IVF clinics worldwide, including recent development of comprehensive chromosome screening of all 23 pairs of chromosomes by microarrays for aneuploidy screening. The routine preimplantation and prenatal genetic diagnosis (PND) require testing in an aggressive manner. These procedures may be invasive to the growing embryo and fetus and potentially could compromise the clinical outcome. Therefore the aim of this review is to summarize not only the new knowledge on preimplantation and prenatal genetic diagnosis in humans, but also on the development of potential noninvasive embryo and fetal testing that might play an important role in the future. PMID:24783200

  1. 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

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

    PubMed

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

    2014-10-01

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

  3. Prenatal Diagnosis: A Directive Approach to Genetic Counseling Using Decision Analysis 1

    PubMed Central

    Pauker, Susan P.; Pauker, Stephen G.

    1977-01-01

    The decision which prospective parents face concerning mid-trimester amniocentesis for prenatal diagnosis was examined by decision analysis. The prospective parents' decision depends on the likelihood of the birth of a child affected by a genetic disorder, the risk of amniocentesis, and the probability that the diagnoses provided by the amniocentesis will be correct. The couple's decision must also depend on their attitudes toward each possible outcome. The likelihoods of the outcomes can be obtained from appropriate medical consultation, while the relative costs or burdens of the outcomes should be obtained from the prospective parents. A truly informed decision for this couple can then be formulated from these probabilities and values, thus allowing genetic counseling to be more directive. The technique is illustrated for the prenatal diagnosis of Down's syndrome, meningomyelocele, and Duchenne muscular dystrophy. PMID:142379

  4. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

  7. Genetic Diagnosis of Two Dopa-Responsive Dystonia Families by Exome Sequencing

    PubMed Central

    Sun, Zhan-fang; Zhang, Yu-han; Guo, Ji-feng; Sun, Qi-ying; Mei, Jun-pu; Zhou, Han-lin; Guan, Li-ping; Tian, Jin-yong; Hu, Zheng-mao; Li, Jia-da; Xia, Kun; Yan, Xin-xiang; Tang, Bei-sha

    2014-01-01

    Dopa-responsive dystonia, a rare disorder typically presenting in early childhood with lower limb dystonia and gait abnormality, responds well to levodopa. However, it is often misdiagnosed with the wide spectrum of phenotypes. By exome sequencing, we make a rapid genetic diagnosis for two atypical dopa-responsive dystonia pedigrees. One pedigree, presented with prominent parkinsonism, was misdiagnosed as Parkinson's disease until a known mutation in GCH1 (GTP cyclohydrolase 1) gene (NM_000161.2: c.631_632delAT, p.Met211ValfsX38) was found. The other pedigree was detected with a new compound heterozygous mutation in TH (tyrosine hydroxylase) gene [(NM_000360.3: c.911C>T, p.Ala304Val) and (NM_000360.3: c.1358G>A, p.Arg453His)], whose proband, a pregnant woman, required a rapid and less-biased genetic diagnosis. In conclusion, we demonstrated that exome sequencing could provide a precise and rapid genetic testing in the diagnosis of Mendelian diseases, especially for diseases with wide phenotypes. PMID:25181484

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

    SciTech Connect

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

    1993-10-01

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

  9. Validation of next-generation sequencing technologies in genetic diagnosis of dementia.

    PubMed

    Beck, John; Pittman, Alan; Adamson, Gary; Campbell, Tracy; Kenny, Joanna; Houlden, Henry; Rohrer, Jon D; de Silva, Rohan; Shoai, Maryam; Uphill, James; Poulter, Mark; Hardy, John; Mummery, Catherine J; Warren, Jason D; Schott, Jonathan M; Fox, Nick C; Rossor, Martin N; Collinge, John; Mead, Simon

    2014-01-01

    Identification of a specific genetic cause of early onset dementia (EOD) is important but can be difficult because of pleiotropy, locus heterogeneity and accessibility of gene tests. Here we assess the use of next generation sequencing (NGS) technologies as a quick, accurate and cost effective method to determine genetic diagnosis in EOD. We developed gene panel based technologies to assess 16 genes known to harbour mutations causal of dementia and combined these with PCR based assessments of the C9orf72 hexanucleotide repeat expansion and the octapeptide repeat region of PRNP. In a blinded study of 95 samples we show very high sensitivity and specificity are achievable using either Ion Torrent or MiSeq sequencing platforms. Modifications to the gene panel permit accurate detection of structural variation in APP. In 2/10 samples which had been selected because they possess a variant of uncertain significance the new technology discovered a causal mutation in genes not previously sequenced. A large proportion (23/85) of samples showed genetic variants of uncertain significance in addition to known mutations. The MRC Dementia Gene Panel and similar technologies are likely to be transformational in EOD diagnosis with a significant impact on the proportion of patients in whom a genetic cause is identified. PMID:23998997

  10. 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

  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.

  12. Genetic diagnosis of PLP gene duplications/deletions in patients with Pelizaeus-Merzbacher disease.

    PubMed

    Gao, Q; Thurston, V C; Vance, G H; Dlouhy, S R; Hodes, M E

    2005-11-01

    Genetic diagnosis of PLP gene duplications/deletions in patients with Pelizaeus-Merzbacher disease.PMD is an X-linked recessive disorder due to a proteolipid protein (PLP) deficiency. Duplications of PLP gene were shown to be the principle cause of the disorder, accounting for an estimated 50-70% of cases. To define a simple and reliable method for genetic diagnosis of PMD, a group of 42 patients with clinical manifestation of PMD was analyzed by means of real-time quantitative PCR. Parallel fluorescence in situ hybridization (FISH) analysis was performed on the same group of patients. Real-time PCR found seventeen samples had increased gene dosage, whereas FISH detected sixteen duplicated samples. Both methods identified a sample with PLP gene deletion. Our results indicate that real-time PCR is a sensitive and reliable method for the detection of gene duplications/deletions. We further discussed the advantages and limitations of each method in clinical diagnosis of PMD. PMID:16207216

  13. The utility of exome sequencing for genetic diagnosis in a familial microcephaly epilepsy syndrome

    PubMed Central

    2014-01-01

    Background Despite remarkable advances in genetic testing, many adults with syndromic epilepsy remain without a molecular diagnosis. The challenge in providing genetic testing for this patient population lies in the extensive genetic heterogeneity associated with epilepsy. Even for the subset of epilepsy patients that present with a defining feature, such as microcephaly, the number of possible genes that would require interrogation by Sanger sequencing is extensive and often prohibitively expensive. Case presentation We report a family of French Canadian descent with four adult children affected with severe intellectual disability, epilepsy and microcephaly born to consanguineous parents and evaluated by the Genetics Service to provide informed genetic counseling to unaffected family members regarding possible recurrence risks. We used whole-exome sequencing (WES) of DNA from one affected sibling as a first-line diagnostic tool and compared the prioritization of variants using two strategies: 1) focusing on genes with homozygous variants; and, 2) focusing on genes associated with microcephaly. Both approaches prioritized the same homozygous novel frameshift mutation (p.Arg608Serfs*26) in WDR62, a gene known to cause autosomal recessive primary microcephaly. Sanger sequencing confirmed the presence of the homozygous mutation in the other three affected siblings. Conclusions WES and subsequent filtering of the rare variants in a single affected family member led to the rapid and cost-effective identification of a novel homozygous frameshift mutation in WDR62, thereby explaining the severe neurodevelopmental disorder in this family and facilitating genetic counseling. Our findings support WES as an effective first-line diagnostic tool in families presenting with rare genetically heterogeneous neurological disorders. PMID:24479948

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

    PubMed

    Elveren, Erhan; Yumu?ak, Nejat

    2011-06-01

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

  15. Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome: a treatable genetic liver disease warranting urgent diagnosis.

    PubMed

    Lee, Hencher H C; Poon, K H; Lai, C K; Au, K M; Siu, T S; Lai, Judy P S; Mak, Chloe M; Yuen, Y P; Lam, C W; Chan, Albert Y W

    2014-02-01

    Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome is an autosomal recessive disorder caused by a defect in ornithine translocase. This condition leads to variable clinical presentations, including episodic hyperammonaemia, hepatic derangement, and chronic neurological manifestations. Fewer than 100 affected patients have been reported worldwide. Here we report the first two cases in Hong Kong Chinese, who were compound heterozygous siblings for c.535C>T (p.Arg179*) and c.815C>T (p.Thr272Ile) in the SLC25A15 gene. When the mother refused prenatal diagnosis for the second pregnancy, urgent genetic testing provided the definitive diagnosis within 24 hours to enable specific treatment. Optimal management of these two patients relied on the concerted efforts of a multidisciplinary team and illustrates the importance of an expanded newborn screening service for early detection and treatment of inherited metabolic diseases. PMID:24473688

  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. 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

  18. 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

  19. Leukotriene E4 activates human Th2 cells for exaggerated pro-inflammatory cytokine production in response to PGD2

    PubMed Central

    Xue, Luzheng; Barrow, Anna; Fleming, Vicki M.; Hunter, Michael G.; Ogg, Graham; Klenerman, Paul; Pettipher, Roy

    2011-01-01

    PGD2 exerts a number of pro-inflammatory responses through a high affinity interaction with chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) and has been detected at high concentrations at sites of allergic inflammation. Since cysteinyl leukotrienes (cysLTs) are also produced during the allergic response we investigated the possibility that cysLTs may modulate the response of human Th2 cells to PGD2. PGD2 induced concentration-dependent Th2 cytokine production in the absence of TCR stimulation. Leukotrienes D4 (LTD4) and E4 (LTE4) also stimulated the cytokine production but were much less active than PGD2. However, when combined with PGD2, cysLTs caused a greater than additive enhancement of the response, with LTE4 being most effective in activating Th2 cells. LTE4 enhanced calcium mobilisation in response to PGD2 in Th2 cells without affecting endogenous PGD2 production or CRTH2 receptor expression. The effect of LTE4 was inhibited by montelukast but not by the P2Y12 antagonistmethylthioadenosine 5?-monophosphate. The enhancing effect was also evident with endogenous cysLTs produced from immunologically activated mast cells since inhibition of cysLT action by montelukast or cysLT sythesis by MK886, an inhibitor of 5-LO-activating protein, reduced the response of Th2 cells to the levels produced by PGD2 alone. These findings reveal that cysLTs, in particular LTE4, have a significant pro-inflammatory impact on T cells and demonstrate their effects on Th2 cells are mediated by a montelukast-sensitive receptor. PMID:22174450

  20. Genetically identified complete hydatidiform mole coexisting with a live twin fetus: comparison with conventional diagnosis.

    PubMed

    Sumigama, Seiji; Itakura, Atsuo; Yamamoto, Toshimichi; Nagasaka, Tetsuro; Yamamoto, Eiko; Ino, Kazuhiko; Kikkawa, Fumitaka

    2007-01-01

    Twin pregnancy consisting of a complete hydatidiform mole (CHM) along with a live co-existing fetus is a rare entity and difficult to diagnose. A 37-year-old Japanese woman demonstrated a living fetus, a placenta and a multicystic mass within one gestational sac on ultrasound at 10 weeks. Termination of the pregnancy was performed, and the specimen was classified as partial mole by macro- and microscopic findings. The karyotype of the molar tissue was 46XX. DNA polymorphism analysis demonstrated that fetal DNA showed bi-parental origin while molar DNA showed paternal origin only. Thus, this case was erroneously classified by ultrasonography, macroscopic and pathologic findings, then correctly diagnosed as a twin pregnancy with a CHM and co-existing normal twin fetus by DNA polymorphism analysis. Immunohistochemistry of p57(KIP2), the paternally imprinted and maternally expressed gene, supported the genetic diagnosis. This case suggested that conventional diagnostic methods were inadequate for accurate diagnosis of CHM with a co-existing fetus. DNA polymorphism analysis should be requested for the diagnosis of hydatidiform mole, especially in cases where it is difficult to discriminate between partial hydatidiform mole and CHM with a co-existing fetus. PMID:17664887

  1. 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

  2. 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

  3. Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of colorectal cancer.

    PubMed

    Coppedè, Fabio; Lopomo, Angela; Spisni, Roberto; Migliore, Lucia

    2014-01-28

    Colorectal cancer (CRC) is one of the most common cancer worldwide and results from the accumulation of mutations and epimutations in colonic mucosa cells ultimately leading to cell proliferation and metastasis. Unfortunately, CRC prognosis is still poor and the search of novel diagnostic and prognostic biomarkers is highly desired to prevent CRC-related deaths. The present article aims to summarize the most recent findings concerning the use of either genetic or epigenetic (mainly related to DNA methylation) biomarkers for CRC diagnosis, prognosis, and response to treatment. Recent large-scale DNA methylation studies suggest that CRC can be divided into several subtypes according to the frequency of DNA methylation and those of mutations in key CRC genes, and that this is reflected by different prognostic outcomes. Increasing evidence suggests that the analysis of DNA methylation in blood or fecal specimens could represent a valuable non-invasive diagnostic tool for CRC. Moreover, a broad spectrum of studies indicates that the inter-individual response to chemotherapeutic treatments depends on both epigenetic modifications and genetic mutations occurring in colorectal cancer cells, thereby opening the way for a personalized medicine. Overall, combining genetic and epigenetic data might represent the most promising tool for a proper diagnostic, prognostic and therapeutic approach. PMID:24574767

  4. Focus on genetic and epigenetic events of colorectal cancer pathogenesis: implications for molecular diagnosis.

    PubMed

    Zoratto, Federica; Rossi, Luigi; Verrico, Monica; Papa, Anselmo; Basso, Enrico; Zullo, Angelo; Tomao, Luigi; Romiti, Adriana; Lo Russo, Giuseppe; Tomao, Silverio

    2014-07-01

    Originally, colorectal cancer (CRC) tumorigenesis was understood as a multistep process that involved accumulation of tumor suppressor genes and oncogenes mutations, such as APC, TP53 and KRAS. However, this assumption proposed a relatively limited repertoire of genetic alterations. In the last decade, there have been major advances in knowledge of multiple molecular pathways involved in CRC pathogenesis, particularly regarding cytogenetic and epigenetic events. Microsatellite instability, chromosomal instability and CpG island methylator phenotype are the most analyzed cytogenetic changes, while DNA methylation, modifications in histone proteins and microRNAs (miRNAs) were analyzed in the field of epigenetic alterations. Therefore, CRC development results from interactions at many levels between genetic and epigenetic amendments. Furthermore, hereditary cancer syndrome and individual or environmental risk factors should not be ignored. The difficulties in this setting are addressed to understand the molecular basis of individual susceptibility to CRC and to determine the roles of genetic and epigenetic alterations, in order to yield more effective prevention strategies in CRC patients and directing their treatment. This review summarizes the most investigated biomolecular pathways involved in CRC pathogenesis, their role as biomarkers for early CRC diagnosis and their possible use to stratify susceptible patients into appropriate screening or surveillance programs. PMID:25051912

  5. The research of sensor fault diagnosis based on genetic algorithm and one-against-one support vector machine

    Microsoft Academic Search

    Xu Lishuang; Cai Tao; Deng Fang; Liu Xin

    2011-01-01

    Fault diagnosis based on the wavelet packet decomposition, one-against-one support vector machine (SVM) and genetic algorithm (GA) is proposed in order to realize the real-time sensor fault diagnosis accurately. The input feature vectors of one-against-one SVM are produced by wavelet packet decomposition of the sensor output signal. GA is used to obtain optimal parameters of one-against-one SVM network model automatically,

  6. Label-Free Electrochemical Diagnosis of Viral Antigens with Genetically Engineered Fusion Protein

    PubMed Central

    Heo, Nam Su; Zheng, Shun; Yang, MinHo; Lee, Seok Jae; Lee, Sang Yup; Kim, Hwa-Jung; Park, Jung Youn; Lee, Chang-Soo; Park, Tae Jung

    2012-01-01

    We have developed a simple electrochemical biosensing strategy for the label-free diagnosis of hepatitis B virus (HBV) on a gold electrode surface. Gold-binding polypeptide (GBP) fused with single-chain antibody (ScFv) against HBV surface antigen (HBsAg), in forms of genetically engineered protein, was utilized. This GBP-ScFv fusion protein can directly bind onto the gold substrate with the strong binding affinity between the GBP and the gold surface, while the recognition site orients toward the sample for target binding at the same time. Furthermore, this one-step immobilization strategy greatly simplifies a fabrication process without any chemical modification as well as maintaining activity of biological recognition elements. This system allows specific immobilization of proteins and sensitive detection of targets, which were verified by surface plasmon resonance analysis and successfully applied to electrochemical cyclic voltammetry and impedance spectroscopy upto 0.14 ng/mL HBsAg. PMID:23112590

  7. Evidence-based recommendations for genetic diagnosis of familial Mediterranean fever.

    PubMed

    Giancane, Gabriella; Ter Haar, Nienke M; Wulffraat, Nico; Vastert, Sebastiaan J; Barron, Karyl; Hentgen, Veronique; Kallinich, Tilmann; Ozdogan, Huri; Anton, Jordi; Brogan, Paul; Cantarini, Luca; Frenkel, Joost; Galeotti, Caroline; Gattorno, Marco; Grateau, Gilles; Hofer, Michael; Kone-Paut, Isabelle; Kuemmerle-Deschner, Jasmin; Lachmann, Helen J; Simon, Anna; Demirkaya, Erkan; Feldman, Brian; Uziel, Yosef; Ozen, Seza

    2015-04-01

    Familial Mediterranean fever (FMF) is a disease of early onset which can lead to significant morbidity. In 2012, Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched with the aim of optimising and disseminating diagnostic and management regimens for children and young adults with rheumatic diseases. The objective was to establish recommendations for FMF focusing on provision of diagnostic tools for inexperienced clinicians particularly regarding interpretation of MEFV mutations. Evidence-based recommendations were developed using the European League against Rheumatism standard operating procedure. An expert committee of paediatric rheumatologists defined search terms for the systematic literature review. Two independent experts scored articles for validity and level of evidence. Recommendations derived from the literature were evaluated by an online survey and statements with less than 80% agreement were reformulated. Subsequently, all recommendations were discussed at a consensus meeting using the nominal group technique and were accepted if more than 80% agreement was reached. The literature search yielded 3386 articles, of which 25 were considered relevant and scored for validity and level of evidence. In total, 17 articles were scored valid and used to formulate the recommendations. Eight recommendations were accepted with 100% agreement after the consensus meeting. Topics covered were clinical versus genetic diagnosis of FMF, genotype-phenotype correlation, genotype-age at onset correlation, silent carriers and risk of amyloid A (AA) amyloidosis, and role of the specialist in FMF diagnosis. The SHARE initiative provides recommendations for diagnosing FMF aimed at facilitating improved and uniform care throughout Europe. PMID:25628446

  8. Diabetes Mellitus in Neonates and Infants: Genetic Heterogeneity, Clinical Approach to Diagnosis, and Therapeutic Options

    PubMed Central

    Rubio-Cabezas, Oscar; Ellard, Sian

    2013-01-01

    Over the last decade, we have witnessed major advances in the understanding of the molecular basis of neonatal and infancy-onset diabetes. It is now widely accepted that diabetes presenting before 6 months of age is unlikely to be autoimmune type 1 diabetes. The vast majority of such patients will have a monogenic disorder responsible for the disease and, in some of them, also for a number of other associated extrapancreatic clinical features. Reaching a molecular diagnosis will have immediate clinical consequences for about half of affected patients, as identification of a mutation in either of the two genes encoding the ATP-sensitive potassium channel allows switching from insulin injections to oral sulphonylureas. It also facilitates genetic counselling within the affected families and predicts clinical prognosis. Importantly, monogenic diabetes seems not to be limited to the first 6 months but extends to some extent into the second half of the first year of life, when type 1 diabetes is the more common cause of diabetes. From a scientific perspective, the identification of novel genetic aetiologies has provided important new knowledge regarding the development and function of the human pancreas. PMID:24051999

  9. Access to medical-assisted reproduction and pgd in Italian law: a deadly blow to an illiberal statute? commentary to the European Court on Human Rights's decision Costa and Pavan v Italy (ECtHR, 28 August 2012, App. 54270/2010).

    PubMed

    Biondi, Stefano

    2013-01-01

    This article provides an account of the European Court on Human Rights' Second Section decision in the case Costa and Pavan v Italy. The judgment found that the Italian Statute on Assisted Reproduction (Law 40/2004), and particularly its prohibition to use in vitro fertilisation and pre-implantation genetic diagnosis (PGD) to prevent the birth of children affected by genetically transmissible conditions, breached Article 8 of the European Convention on Human Rights (ECHR). In fact, the statute in question permits only infertile people to access medically assisted reproduction techniques and forbids PGD and embryo selection. The Court regarded that the rationale of these prohibitions-identified by the Italian Government with the need to prevent eugenic practices as well as to protect the health of the unborn and of the woman-was at odds with the fact that Italian law allows pre-natal screening and therapeutic abortions in case foetal abnormalities are diagnosed. In order to clarify the decision's significance, the paper goes on to analyse the rationale of Law 40/2004 in the Italian legal and political context. Emphasis is placed on the fact that this statute is extremely controversial at domestic level, because many of its provisions-including those considered by the Strasbourg Court-are inherently contradictory and contrast with the settled constitutional principles on abortion, as many domestic authorities highlighted. In this context, should the commented decision be confirmed by the Grand Chamber, it may provide a basis to bring consistency back to the Italian regulation of assisted reproduction. Finally, the paper considers the appeal lodged by the Italian Government to the Grand Chamber, and in particular the contention that the European Court had failed to respect Italy's margin of appreciation. In this regard, it is argued that, under Law 40/2004, individuals face illogical and discriminatory restrictions to their right to private and family life and that therefore, even if an outright violation of Article 8 ECHR could not be found, there appears to be at least a breach of Article 8 in conjunction with Article 14 ECHR. PMID:23552505

  10. 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

  11. Genetic diagnosis of Charcot-Marie-Tooth disease in a population by next-generation sequencing.

    PubMed

    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

  12. The Effect of Ddt on the Polymorphism at the G6pd and Pgd Loci in DROSOPHILA MELANOGASTER

    PubMed Central

    Bijlsma, R.; Kerver, J. W. M.

    1983-01-01

    For the degradation of DDT and other chlorohydrocarbon insecticides energy in the form of NADPH is needed which for the greater part is supplied by the pentose phosphate shunt. Therefore the influence of DDT on the polymorphism at the G6pd and Pgd loci in Drosophila melanogaster was investigated by studying its effect on egg to adult survival and adult survival. The results show the existence of significant differences in fitness between the different genotypes of the two loci for both components. It is found that the effect of DDT supplementation differs significantly from the effect of sodium octanoate addition. DDT treatment also increases the activity of the pentose phosphate shunt as measured by the activity of G6PD and 6PGD. In larvae a 50% increase in activity is found and in adults a 100% increase. As there is little doubt that the activities of G6PD and 6PGD are somehow correlated with the fitness of flies, the data are discussed in relation to the in vitro and in vivo differences in activity between the different allozymes of both G6PD and 6PGD. PMID:6404694

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

    PubMed Central

    Ashkinadze, E.; Rosen, T.; Brooks, SS.; Katsanis, N.; Davis, EE.

    2013-01-01

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

  14. Quantification of major urinary metabolites of PGE2 and PGD2 in cystic fibrosis: correlation with disease severity.

    PubMed

    Jabr, Suha; Gartner, Silvia; Milne, Ginger L; Roca-Ferrer, Jordi; Casas, Josefina; Moreno, Antonio; Gelpí, Emilio; Picado, César

    2013-08-01

    Cystic fibrosis transmembrane conductance (CFTR) alterations are involved in the overproduction of prostaglandins (PG) in CF in vitro. We assessed the relationship between PGE-M and PGD-M urinary metabolites of PGE2 and PGD2 and CF severity. Twenty-four controls and 35 CF patients were recruited. PGE-M and PGD-M levels were measured by liquid chromatography/mass spectrometry and results were expressed as median and 25th-75th interquartile of ng/mg creatinine (Cr). PGE-M (15.63; 9.07-43.35ng/mg Cr) and PGD-M (2.16; 1.43-3.53ng/mg Cr) concentrations were higher in CF than in controls: PGE-M, (6.63; 4.35-8.60ng/mg Cr); PGD-M (1.23; 0.96-1.54ng/mg Cr). There was no correlation between metabolite levels and spirometric values. Patients with pancreatic insufficiency (n=29) had higher PGE-M levels (19.09; 9.36-52.69ng/mg Cr) than those with conserved function (n=6) (9.61; 5.78-14.34ng/mg Cr). PGE-M levels were associated with genotype severity: mild (7.14; 5.76-8.76, n=8), moderate (16.67; 13.67-28.62ng/mg Cr, n=5) and severe (22.82; 10.67-84.13ng/mg Cr). Our study confirms the key role of CFTR in the regulation of the cyclooxygenase pathway of arachidonic acid metabolism found in in vitro studies. PMID:23791427

  15. Genetics Evaluation Guidelines for the Etiologic Diagnosis of Congenital Hearing Loss

    PubMed Central

    2002-01-01

    The advent of hearing screening in newborns in many states has led to an increase in the use of genetic testing and related genetic services in the follow-up of infants with hearing loss. A significant proportion of those with congenital hearing loss have genetic etiologies underlying their hearing loss. To ensure that those identified with congenital hearing loss receive the genetic services appropriate to their conditions, the Maternal and Child Health Bureau of the Health Resources and Services Administration funded the American College of Medical Genetics to convene an expert panel to develop guidelines for the genetic evaluation of congential hearing loss. After a brief overview of the current knowledge of hearing loss, newborn screening, and newborn hearing screening, we provide an overview of genetic services and a guideline that describes how best to ensure that patients receive appropriate genetic services. The significant contribution of genetic factors to these conditions combined with the rapid evolution of knowledge about the genetics of these conditions overlaid with the inherently multidisciplinary nature of genetic services provides an example of a condition for which a well-integrated multidisciplinary approach to care is clearly needed. PMID:12180152

  16. American College of Medical Genetics and Genomics guideline for the clinical evaluation and etiologic diagnosis of hearing loss.

    PubMed

    Alford, Raye L; Arnos, Kathleen S; Fox, Michelle; Lin, Jerry W; Palmer, Christina G; Pandya, Arti; Rehm, Heidi L; Robin, Nathaniel H; Scott, Daryl A; Yoshinaga-Itano, Christine

    2014-04-01

    Hearing loss is a common and complex condition that can occur at any age, can be inherited or acquired, and is associated with a remarkably wide array of etiologies. The diverse causes of hearing loss, combined with the highly variable and often overlapping presentations of different forms of hearing loss, challenge the ability of traditional clinical evaluations to arrive at an etiologic diagnosis for many deaf and hard-of-hearing individuals. However, identifying the etiology of a hearing loss may affect clinical management, improve prognostic accuracy, and refine genetic counseling and assessment of the likelihood of recurrence for relatives of deaf and hard-of-hearing individuals. Linguistic and cultural identities associated with being deaf or hard of hearing can complicate access to and the effectiveness of clinical care. These concerns can be minimized when genetic and other health-care services are provided in a linguistically and culturally sensitive manner. This guideline offers information about the frequency, causes, and presentations of hearing loss and suggests approaches to the clinical evaluation of deaf and hard-of-hearing individuals aimed at identifying an etiologic diagnosis and providing informative and effective patient education and genetic counseling. PMID:24651602

  17. An automatic scanning method for high throughput microscopic system to facilitate medical genetic diagnosis: an initial study

    NASA Astrophysics Data System (ADS)

    Qiu, Yuchen; Chen, Xiaodong; Li, Zheng; Li, Yuhua; Chen, Wei R.; Zheng, Bin; Li, Shibo; Liu, Hong

    2012-03-01

    The purpose of this paper is to report a new automatic scanning scheme for high throughput microscopic systems aiming to facilitate disease diagnosis in genetic laboratories. To minimize the impact of the random vibration and mechanical drifting of the scanning stage in microscopic image acquisition, auto-focusing operations are usually applied repeatedly during the scanning process. Such methods ensure the acquisition of well focused images for clinical diagnosis, but are time consuming. The technique investigated in this preliminary study applies the auto-focusing operations at a limited number of locations on the slide. For the rest of the imaging field, the focusing position is quickly adjusted through linear interpolation. In this initial validation study, blood pathological slides containing both metaphase and interphase cells are scanned. For a selected area of 6.9mm×6.9mm, a number of 2×2, 3×2, 3×3, and 4×4 positions are evenly sampled for auto-focusing operations. Respectively, 25, 29, 40, and 41 clinically meaningful cells are identified for each sampling scheme. For the specific case investigated, the results demonstrate that the 4 position auto-focusing scheme could obtain the adequate number of clinically meaningful cells for the diagnosis. The schemes with more auto-focusing operations provide an option for high reliability diagnosis when clinically necessary. More comprehensive research is planned, and that may lead to optimal design of trade-off for developing the scanning scheme of the high throughput microscopic systems.

  18. 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. (Southwest Foundation for Biomedical Research, San Antonio, TX (United States))

    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.

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

    SciTech Connect

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

    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.

  20. Permissibility of prenatal diagnosis and abortion for fetuses with severe genetic disorder: type 1 spinal muscular atrophy.

    PubMed

    Sasongko, Teguh H; Salmi, Abd Razak; Zilfalil, Bin Alwi; Albar, Mohammed Ali; Mohd Hussin, Zabidi Azhar

    2010-01-01

    Abortion has been largely avoided in Muslim communities. However, Islamic jurists have established rigorous parameters enabling abortion of fetuses with severe congenital abnormalities. This decision-making process has been hindered by an inability to predict the severity of such prenatally-diagnosed conditions, especially in genetic disorders with clinical heterogeneity, such as spinal muscular atrophy (SMA). Heterogeneous phenotypes of SMA range from extremely severe type 1 to very mild type 4. Advances in molecular genetics have made it possible to perform prenatal diagnosis and to predict the types of SMA with its potential subsequent severity. Such techniques will make it possible for clinicians working in predominantly Muslim countries to counsel their patients accurately and in harmony with their religious beliefs. In this paper, we discuss and postulate that with our current knowledge of determining SMA types and severity with great accuracy, abortion is legally applicable for type 1 SMA. PMID:21060155

  1. Remote diagnosis and monitoring of complex industrial systems using a genetic algorithm approach

    Microsoft Academic Search

    Carlos Rojas-GuzmAn; Mark A. Kramer

    1994-01-01

    Remote diagnosis of industrial and manufacturing facilities constitutes a feasible alternative at high-risk or remote sites where unmanned operation is preferred. Computer-aided diagnostic tools can reduce downtime by providing support to remote monitoring centers and on-site plant operators. This paper describes a novel technique to perform on-line remote monitoring and diagnosis of industrial and manufacturing systems based on Bayesian belief

  2. Skill and tactic diagnosis for table tennis matches based on artificial neural network and genetic algorithm

    Microsoft Academic Search

    Wenwu Mao; Lijuan Yu; Hui Zhang; Haihang Wang; Peiliang Ling; Jie Wang

    2010-01-01

    Due to the complexity, multiplicity and randomness of table tennis matches, the paper presents skill and tactic diagnostic model for table-tennis matches of elite athletes with artificial neural network and genetic algorithm. A back propagation network is used to build basic structure of the model and genetic algorithm is established to optimize the connection weights and threshold values of the

  3. Existing challenges associated with offering prenatal genetic diagnosis in an Arab society in the Sultanate of Oman.

    PubMed

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

    2014-12-01

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

  4. Genetics Gets Personal: Teaching Ethical, Legal and Social

    E-print Network

    Sabatini, David M.

    anemia (disorder of DNA repair) Treatment: PGD, umbilical cord blood stem cells http://tvnoviny.sk/sekciaGenetics Gets Personal: Teaching Ethical, Legal and Social Issues in Personal Genetics Marnie-time mothers in the US, 2003: 25.2 Sources: census.gov, cdc.org, NYT #12;www.pgEd.org pgEd's goal

  5. Preimplantation genetic diagnosis for couples at high risk of Down syndrome pregnancy owing to parental translocation or mosaicism

    PubMed Central

    Conn, C.; Cozzi, J.; Harper, J.; Winston, R.; Delhanty, J.

    1999-01-01

    The population risk for trisomy 21 is 1 in 700 births but some couples are at a much higher risk owing to parental translocation or mosaicism. We report on the first attempt to carry out preimplantation genetic diagnosis for two such couples using cleavage stage embryo biopsy and dual colour FISH analysis. Each couple underwent two treatment cycles. Couple 1 (suspected gonadal mosaicism for trisomy 21) had two embryos normal for chromosome 21 transferred, but no pregnancy resulted; 64% (7/11) unfertilised oocytes/embryos showed chromosome 21 aneuploidy. Couple 2 (46,XX,t(6;21)(q13;q22.3)) had a single embryo transferred resulting in a biochemical pregnancy; 91% (10/11) oocytes/embryos showed chromosome 21 imbalance, most resulting from 3:1 segregation of this translocation at gametogenesis. The opportunity to test embryos before implantation enables the outcome of female meiosis to be studied for the first time and the recurrence risk for a Down syndrome pregnancy to be assessed.???Keywords: preimplantation genetic diagnosis; Down syndrome; reciprocal translocation; gonadal mosaicism PMID:9950365

  6. Fault diagnosis of power transformer based on support vector machine with genetic algorithm

    Microsoft Academic Search

    Sheng-wei Fei; Xiao-bin Zhang

    2009-01-01

    Diagnosis of potential faults concealed inside power transformers is the key of ensuring stable electrical power supply to consumers. Support vector machine (SVM) is a new machine learning method based on the statistical learning theory, which is a powerful tool for solving the problem with small sampling, nonlinearity and high dimension. The selection of SVM parameters has an important influence

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

    E-print Network

    Yao, Xin

    Spectrometry Proteomics Henri F. Tedom Noumbi School of Computer Science, University of Birmingham msc45hft spectrometry as a proteomic tool has recently been applied to early- stage cancer diagnosis. It enables-throughput mass spectrometry data for ovarian cancer detection; Cercia, School of Computer Science, The university

  8. pGD vectors: versatile tools for the expression of green and red fluorescent protein fusions in agroinfiltrated plant leaves.

    PubMed

    Goodin, Michael M; Dietzgen, Ralf G; Schichnes, Denise; Ruzin, Steven; Jackson, Andrew O

    2002-08-01

    We have constructed a matched set of binary vectors designated pGD, pGDG and pGDR for the expression and co-localization of native proteins and GFP or DsRed fusions in large numbers of plant cells. The utility of these vectors following agroinfiltration into leaves has been demonstrated with four genes from Sonchus yellow net virus, a plant nucleorhabdovirus, and with a nucleolar marker protein. Of the three SYNV proteins tested, sc4 gave identical localization patterns at the cell wall and nucleus when fused to GFP or DsRed. However, some differences in expression patterns were observed depending on whether DsRed or GFP was the fusion partner. In this regard, the DsRed:P fusion showed a similar pattern of localization to GFP:P, but localized foci appeared in the nucleus and near the periphery of the nucleus. Nevertheless, the viral nucleocapsid protein, expressed as a GFP:N fusion, co-localized with DsRed:P in a subnuclear locale in agreement with our previous observations (Goodin et al., 2001). This locale appears to be distinct from the nucleolus as indicated by co-expression of the N protein, DsRed:P and a nucleolar marker AtFib1 fused to GFP. The SYNV M protein, which is believed to be particularly prone to oligomerization, was detectable only as a GFP fusion. Our results indicate that agroinfiltration with bacteria containing the pGD vectors is extremely useful for transient expression of several proteins in a high proportion of the cells of Nicotiana benthamiana leaves. The GFP and DsRed elements incorporated into the pGD system should greatly increase the ease of visualizing co-localization and interactions of proteins in a variety of experimental dicotyledonous hosts. PMID:12164816

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

    E-print Network

    Fernandez, Thomas

    ' C' D' B F' D (sexual reproduction) Reproduction (asexual reproduction) B A C B A X Z Mutation Y Operators used in Genetic Programming In biological evolution, individuals are created by either sexual or asexual reproduction, each individual taking on some of the characteristics of its parents. The most

  10. 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

  11. Comprehensive massive parallel DNA sequencing strategy for the genetic diagnosis of the neuro-cardio-facio-cutaneous syndromes.

    PubMed

    Justino, Ana; Dias, Patrícia; João Pina, Maria; Sousa, Sónia; Cirnes, Luís; Berta Sousa, Ana; Carlos Machado, José; Costa, José Luis

    2015-03-01

    Variants in 11 genes of the RAS/MAPK signaling pathway have been causally linked to the neuro-cardio-facio-cutaneous syndromes group (NCFCS). Recently, A2ML1 and RIT1 were also associated with these syndromes. Because of the genetic and clinical heterogeneity of NCFCS, it is challenging to define strategies for their molecular diagnosis. The aim of this study was to develop and validate a massive parallel sequencing (MPS)-based strategy for the molecular diagnosis of NCFCS. A multiplex PCR-based strategy for the enrichment of the 13 genes and a variant prioritization pipeline was established. Two sets of genomic DNA samples were studied using the Ion PGM System: (1) training set (n=15) to optimize the strategy and (2) validation set (n=20) to validate and evaluate the power of the new methodology. Sanger sequencing was performed to confirm all variants and low covered regions. All variants identified by Sanger sequencing were detected with our MPS approach. The methodology resulted in an experimental approach with a specificity of 99.0% and a maximum analytical sensitivity of ?98.2% with a confidence of 99%. Importantly, two patients (out of 20) harbored described disease-causing variants in genes that are not routinely tested (RIT1 and SHOC2). The addition of less frequently altered genes increased in ?10% the diagnostic yield of the strategy currently used. The presented workflow provides a comprehensive genetic screening strategy for patients with NCFCS in a fast and cost-efficient manner. This approach demonstrates the potential of a combined MPS-Sanger sequencing-based strategy as an effective diagnostic tool for heterogeneous diseases. PMID:24896146

  12. Self Diagnosis of Lynch Syndrome Using Direct to Consumer Genetic Testing: A Case Study

    Microsoft Academic Search

    Maegan E. Roberts; Douglas L. Riegert-Johnson; Brittany C. Thomas

    2011-01-01

    We are reporting what we believe to be the first published case of patient initiated direct to consumer (DTC) genetic testing\\u000a to test for the presence of a known familial mutation. Our client in this case is from a known MSH2 family; both his\\/her parent and associated grandparent have previously tested positive for the known familial MSH2 mutation. Using 23andme’s

  13. Prenatal diagnosis and genetic analysis of fetal akinesia deformation sequence and multiple pterygium syndrome associated with neuromuscular junction disorders: a review.

    PubMed

    Chen, Chih-Ping

    2012-03-01

    Fetal akinesia deformation sequence is a clinically and genetically heterogeneous disorder characterized by a variable combination of arthrogryposis, fetal akinesia, intrauterine growth restriction, developmental abnormalities such as cystic hygroma, pulmonary hypoplasia, cleft palate, cryptorchidism, cardiac defects and intestinal malrotation, and occasional pterygia of the limbs. Multiple pterygium syndrome is a clinically and genetically heterogeneous disorder characterized by pterygia of the neck, elbows and/or knees, arthrogryposis, and other phenotypic features such as short stature, genital abnormalities, craniofacial abnormalities, clubfoot, kyphoscoliosis, and cardiac abnormalities. Fetal akinesia deformation sequence may phenotypically overlap with the lethal type of multiple pterygium syndrome. This article provides a comprehensive review of prenatal diagnosis and genetic analysis of fetal akinesia deformation sequence and multiple pterygium syndrome associated with neuromuscular junction disorders. Prenatal diagnosis of fetal akinesia along with cystic hygroma, increased nuchal translucency, nuchal edema, hydrops fetalis, arthrogryposis, pterygia, and other structural abnormalities should include a differential diagnosis of neuromuscular junction disorders. Genetic analysis of mutations in the neuromuscular junction genes such as CHRNA1, CHRND, CHRNG, CNTN1, DOK7, RAPSN, and SYNE1 may unveil the pathogenetic cause of fetal akinesia deformation sequence and multiple pterygium syndrome, and the information acquired is helpful for genetic counseling and clinical management. PMID:22482962

  14. 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

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

    SciTech Connect

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

    1994-09-01

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

  16. Genetic variability of foxtail millet ( Setaria italica P. Beauv.)

    Microsoft Academic Search

    M. Jusuf; J. Pernes

    1985-01-01

    The genetic diversity of a world collection of foxtail millet strains (Setaria italica) and some samples of wild populations (Setaria viridis) was studied by means of electrophoresis on five enzymes (10 loci) Est, Acph, Got, Mdh, Pgd. In spite of an overall limited polymorphism, the diversity appeared to be clearly regionalized. The wild populations collected in France and China introduced

  17. Cystic Fibrosis: Prenatal Screening and Diagnosis

    MedlinePLUS

    ... your own sperm and eggs, and then using preimplantation genetic diagnosis to see if the fertilized egg ... each parent for a child to be affected. Preimplantation Genetic Diagnosis: A type of genetic testing that ...

  18. Alport Syndrome Diagnosis

    MedlinePLUS

    ... perform analysis of skin biopsies for Alport Syndrome. Genetic Testing Clinicians in many but not all parts of the world now have access to genetic testing for diagnosis of Alport Syndrome through commercial laboratories ...

  19. Genetics

    MedlinePLUS

    ... 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 ...

  20. 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.

  1. 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

  2. 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.

  3. 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. (Medizinische Universitaet zu Luebeck (Germany) Tufts-New England Medical Center, Boston, MA (United States)); Huang, Q. (Massachusetts Eye and Ear Infirmary, Boston, MA (United States)); Sinnecker, G.H.G.; Kruse, K. (Medizinische Universitaet zu Luebeck (Germany)); Sadeghi-Nejad, A.; Wolfe, H.J. (Tufts-New England Medical Center, Boston, MA (United States)); Yandell, D.W. (Massachusetts Eye and Ear Infirmary, Boston, MA (United States))(Harvard Medical School, Boston, MA (United States) Harvard School of Public Health, Boston, MA (United States))

    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.

  4. Influence of maternal age on the outcome of PGD for aneuploidy screening in patients with recurrent implantation failure.

    PubMed

    Taranissi, Mohamed; El-Toukhy, Tarek; Gorgy, Amin; Verlinsky, Yuri

    2005-05-01

    This study assessed the influence of maternal age on the outcome of aneuploidy screening (AS) cycles for recurrent implantation failure (RIF). One hundred and sixteen couples with a history of RIF underwent 130 cycles of AS. Group A included 78 patients aged < or = 40 years (range 25-40 years) who underwent 86 cycles, while group B included 38 couples aged > or = 41 (range 41-47) who underwent 44 cycles. Fluorescence in-situ hybridization (FISH) analysis of the first and second polar bodies using probes specific for chromosomes 13, 16, 18, 21 and 22 was conducted. Euploid oocytes that cleaved were subsequently tested using the same probes on a single blastomere obtained from day 3 embryos. Chromosomally normal embryos were replaced on day 5 of culture. There was no significant difference between the two groups in the mean numbers of oocytes fertilized normally and oocytes (7.5 +/- 3.2 versus 7.2 +/- 3.6) and embryos tested (4.1 +/- 3 versus 3.4 +/-3). However, the younger age group had a significantly higher proportion of euploid oocytes/embryos, cycles reaching embryo transfer, pregnancy (43 versus 25%), clinical pregnancy (36.1 versus 16.6%) and ongoing delivery (32 versus 12.5%) rates per transfer. Preimplantation genetic diagnosis with AS for recurrent IVF implantation failure using FISH probes is therefore associated with improved outcome in women under 41 years, but has a high cancellation rate and low cycle outcome in older women. PMID:15949221

  5. 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.

  6. Aspirin-intolerant asthma (AIA) assessment using the urinary biomarkers, leukotriene E4 (LTE4) and prostaglandin D2 (PGD2) metabolites.

    PubMed

    Higashi, Noritaka; Taniguchi, Masami; Mita, Haruhisa; Yamaguchi, Hiromichi; Ono, Emiko; Akiyama, Kazuo

    2012-09-01

    The clinical syndrome of aspirin-intolerant asthma (AIA) is characterized by aspirin/nonsteroidal anti-inflammatory drug intolerance, bronchial asthma, and chronic rhinosinusitis with nasal polyposis. AIA reactions are evidently triggered by pharmacological effect of cyclooxygenase-1 inhibitors. Urine sampling is a non-invasive research tool for time-course measurements in clinical investigations. The urinary stable metabolite concentration of arachidonic acid products provides a time-integrated estimate of the production of the parent compounds in vivo. AIA patients exhibits significantly higher urinary concentrations of leukotriene E(4) (LTE(4)) and 1,15-dioxo-9?-hydroxy-2,3,4,5-tetranorprostan-1,20-dioic acid (tetranor-PGDM), a newly identified metabolite of PGD(2), at baseline. This finding suggests the possibility that increased mast cell activation is involved in the pathophysiology of AIA even in a clinically stable condition. In addition, lower urinary concentrations of primary prostaglandin E(2) and 15-epimer of lipoxin A(4) at baseline in the AIA patients suggest that the impaired anti-inflammatory elements may also contribute to the severe clinical outcome of AIA. During the AIA reaction, the urinary concentrations of LTE(4) and PGD(2) metabolites, including tetranor-PGDM significantly and correlatively increase. It is considered that mast cell activation probably is a pathophysiologic hallmark of AIA. However, despite the fact that cyclooxygenease-1 is the dominant in vivo PGD(2) biosynthetic pathway, the precise mechanism underlying the PGD(2) overproduction resulting from the pharmacological effect of cyclooxygenease-1 inhibitors in AIA remains unknown. A comprehensive analysis of the urinary concentration of inflammatory mediators may afford a new research target in elucidating the pathophysiology of AIA. PMID:22627848

  7. 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

  8. Live birth following double-factor pre-implantation genetic diagnosis for both reciprocal translocation and alpha-thalassaemia.

    PubMed

    Lee, Vivian C Y; Chow, Judy F C; Lau, Estella Y L; Yeung, William S B; Ng, Ernest H Y

    2014-06-01

    We report a live birth from a couple with two genetic diseases, namely: reciprocal translocation carrier and alpha-thalassaemia trait, following pre-implantation genetic diagnostic tests. This is the first case in Hong Kong in which the technique of using one blastomere biopsy for two diseases was established, using array comparative genomic hybridisation and polymerase chain reaction. PMID:24914077

  9. Genetics

    Microsoft Academic Search

    1990-01-01

    The author draws on modern research to introduce genetics in a molecular and cellular context. This work covers the structure of DNA and the gene and gene expression, replication, mutation, and recombination, looks at the gene in the context of the cell and organism, describes the elements of genetic analysis and the basic principles of inheritance, and examines classic experiments

  10. Practice Guidelines for Communicating a Prenatal or Postnatal Diagnosis of Down Syndrome: Recommendations of the National Society of Genetic Counselors

    Microsoft Academic Search

    Kathryn B. Sheets; Blythe G. Crissman; Cori D. Feist; Susan L. Sell; Lisa R. Johnson; Kelly C. Donahue; Diane Masser-Frye; Gail S. Brookshire; Amanda M. Carre; Danielle LaGrave; Campbell K. Brasington

    Down syndrome is one of the most common conditions encountered in the genetics clinic. Due to improvements in healthcare,\\u000a educational opportunities, and community inclusion over the past 30 years, the life expectancy and quality of life for individuals\\u000a with Down syndrome have significantly improved. As prenatal screening and diagnostic techniques have become more enhanced\\u000a and widely available, genetic counselors can expect

  11. Genetics

    NSDL National Science Digital Library

    Jennifer Doherty

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

  12. Führt uns die Präimplantationsdiagnostik auf eine Schiefe Ebene?

    Microsoft Academic Search

    Christian Netzer

    1998-01-01

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

  13. Genetics

    NSDL National Science Digital Library

    National Science Teachers Association (NSTA)

    2005-04-01

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

  14. Prevalence of 22q11 microdeletions in DiGeorge and velocardiofacial syndromes: implications for genetic counselling and prenatal diagnosis

    Microsoft Academic Search

    D A Driscoll; J Salvin; B Sellinger; M L Budarf; D M McDonald-McGinn; E H Zackai; B S Emanuel

    1993-01-01

    Deletions of chromosome 22q11 have been seen in association with DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS). In the present study, we analysed samples from 76 patients referred with a diagnosis of either DGS or VCFS to determine the prevalence of 22q11 deletions in these disorders. Using probes and cosmids from the DiGeorge critical region (DGCR), deletions of 22q11 were

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

    Microsoft Academic Search

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

    1989-01-01

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

  16. Prenatal Diagnosis and Genetic Counseling in a Case of Spina Bifida in a Family with Waardenburg Syndrome Type I

    Microsoft Academic Search

    Annegret Kujat; Veit-Peter Veith; Renaldo Faber; Ursula G. Froster

    2007-01-01

    Objective: Waardenburg syndrome type I (WS I) is an autosomal dominant inherited disorder with an incidence of 1:45,000 in Europe. Mutations within the PAX3 gene are responsible for the clinical phenotype ranging from mild facial features to severe malformations detectable in prenatal diagnosis. Methods: Here, we report a four-generation family with several affected members showing various symptoms of WS I.

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

    Microsoft Academic Search

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

    2009-01-01

    The increasing number of laboratories offering molecular genetic analysis of the CFTR gene and the growing use of commercial kits strengthen the need for an update of previous best practice guidelines (published in 2000). The importance of organizing regional or national laboratory networks, to provide both primary and comprehensive CFTR mutation screening, is stressed. Current guidelines focus on strategies for

  20. 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

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

    Microsoft Academic Search

    Maxwell A. Meju

    2000-01-01

    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

  2. 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.

  3. Counselling Families On Genetic Problems

    PubMed Central

    Soltan, H. C.

    1974-01-01

    Genetic counselling is the single most important service which family physicians can render in the area of genetic medicine. The rationale, procedures and effectiveness of genetic counselling are discussed, especially in relation to prenatal diagnosis of genetic disease. PMID:20469111

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

    PubMed

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

    2014-12-01

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

  5. 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 ...

  6. 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...

  7. The diagnosis and management of pre-invasive breast disease: Genetic alterations in pre-invasive lesions

    PubMed Central

    Reis-Filho, Jorge S; Lakhani, Sunil R

    2003-01-01

    The development of modern molecular genetic techniques has allowed breast cancer researchers to clarify the multistep model of breast carcinogenesis. Laser capture microdissection coupled with comparative genomic hybridisation and/or loss-of-heterozygosity methods have confirmed that many pre-invasive lesions of the breast harbour chromosomal abnormalities at loci known to be altered in invasive breast carcinomas. Current data do not provide strong evidence for ductal hyperplasia of usual type as a precursor lesion, although some are monoclonal proliferations; however, atypical hyperplasia and in situ carcinoma appear to be nonobligate precursors. We review current knowledge and the contribution of molecular genetics in the understanding of breast cancer precursors and pre-invasive lesions. PMID:14580249

  8. Multiple mutation analysis of the cystic fibrosis gene in single cells

    Microsoft Academic Search

    Jorge Fernando Sanchez-Garcia; Jordi Benet; Cristina Gutierrez-Mateo; Eugenia Monros

    2005-01-01

    PGD is becoming an alternative to prenatal diagnosis. The combination of IVF techniques with the PCR technology allows for the detection of genetic abnormalities in first polar bodies from oocytes and blastomeres from cleavage-stage embryos. Dealing with a genetic disease with a heterogeneous spectrum of mutations like cystic fibrosis, one of the objectives of centres offering PGD is the application

  9. Challenges in virological diagnosis of HIV -1 transmission from sexual abuse--HIV-1 genetic links are mandatory.

    PubMed

    Ehrnst, Anneka

    2013-02-01

    The purpose of this article is to set forth possible strategies and techniques of analysis to diagnose or identify the source of HIV transmission in victims of sexual abuse. Diagnosis of HIV-1 transmission from sexual abuse is complicated. Timely blood samples are important. The right to confidentiality of the HIV diagnosis may prevent sampling from the offender. Hideous rapes occur during war, which victimize many women. Women delivering a child, seeking an abortion, or having a miscarriage may include victims of sexual abuse. HIV-infected children, where vertical transmission has been excluded, are important for investigation. Men who have sex with men may abuse young men. HIV-infected teenagers with signs of early infection should also be considered. Hundreds of single HIV-1 sequences can be created from one or more blood samples from the case and the alleged abuser. The more HIV-1 genes and sequences that are included, the better the outcomes of the phylogenetic relation. Evidence in support of transmission may be obtained from phylogenetic tree analysis and may also free someone from suspicion. PMID:23387930

  10. 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

  11. 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 ...

  12. Effects of Genetic Susceptibility for Type 2 Diabetes on the Evolution of Glucose Homeostasis Traits Before and After Diabetes Diagnosis

    PubMed Central

    Gautier, Alain; Roussel, Ronan; Lange, Céline; Piguel, Xavier; Cauchi, Stéphane; Vol, Sylviane; Froguel, Philippe; Balkau, Beverley; Bonnet, Fabrice

    2011-01-01

    OBJECTIVE To assess the impact of genetic susceptibility on evolution toward type 2 diabetes (T2D) by analyzing time trajectories of fasting glucose, glycated hemoglobin (HbA1c), insulin sensitivity (homeostasis model assessment [HOMA2%S]), and ?-cell secretion (HOMA2%B) in a large nondiabetic cohort. We also examined whether baseline HbA1c modified the effect of genetic predisposition on the time trajectories. RESEARCH DESIGN AND METHODS Time trajectories were drawn in 4,744 participants from the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.) cohort based on samples collected every 3 years over a 9-year follow-up. Trajectories were analyzed according to the TCF7L2 common variant, a family history of T2D, and a combination of at-risk alleles from nine T2D-associated genes. RESULTS There was a marked decrease in HOMA2%B in parallel to a steep increase in HbA1c over the 3 years before incident diabetes, which was not influenced by genetic predisposition when considered alone. However, after the onset of T2D, the TCF7L2 at-risk variant was associated with a greater decrease in HOMA2%B. There was a joint effect of a family history of T2D with the presence of the TCF7L2 risk allele with a greater rise in HbA1c conferred by the coexistence of a family history and the T risk allele. An HbA1c ?5.7% at baseline was associated with a greater increase in both glycemia and HbA1c levels in the presence of a combination of diabetes at-risk alleles. CONCLUSIONS After incident T2D, TCF7L2 at-risk variants were associated with a faster decrease in ?-cell function compared with those with the CC genotype. There was a joint effect of family history of T2D and TCF7L2 risk variant on the rise in glycemia and the decrease in insulin secretion at the end of follow-up, suggesting the joint influence of the combination of diabetes genetic predisposition with familial factors on the evolution of glycemia over time. PMID:21911746

  13. Genetic diversity and population structure of American Red Angus cattle.

    PubMed

    Márquez, G C; Speidel, S E; Enns, R M; Garrick, D J

    2010-01-01

    The objective of this study was to characterize the population structure and genetic diversity of registered American Red Angus cattle. Inbreeding and average relationship coefficients, effective population size, effective number of founders, and effective number of herds supplying grandparents to the population were calculated from the recorded pedigree. Inbreeding in 1960 was 10.7% and decreased until 1974 at a rate of 0.2% per year, whereas in 1975 inbreeding was 3.2% and increased until 2005 at a rate of 0.02% per year. The numerator relationship coefficients of the 10 individual paternal grandsires (PGS; sires of sires), paternal granddams (PGD; dams of sires), maternal grandsires (MGS; sires of dams), and maternal granddams (MGD; dams of dams) that had the greatest number of registered grandprogeny, with all other registered animals, increased with their birth year from 1960 on. Average numerator relationships of these with all other PGS, PGD, MGS, MGD, bulls, and sires were greater for paternal (PGS, PGD) than maternal (MGS, MGD) pathways. The effective population size was 445, with 649 effective founders. The effective numbers of herds supplying PGS, PGD, MGS, and MGD were 435, 369, 453, and 459, respectively. Inbreeding is at a low level and the effective population size is large. The effective number of founders and effective number of herds supplying grandparents is small in relation to the total number of animals and herds, indicating the disproportionate influence of a few founders and herds on the genetics of the breed. The calculated parameters indicate satisfactory genetic diversity in American Red Angus cattle. PMID:19783699

  14. Genetics

    NSDL National Science Digital Library

    Miss Goodfellow

    2007-10-23

    Genetics is the branch of biology that studies the ways in which hereditary information is passed on from the parents to their offspring. As we study this unit, I will be asking you to visit the following websites to emphasize concepts brought up during class. DNA Structure and Replication Build a DNA molecule Use this website to practice matching up complementary nucleotides in the DNA molecule. How DNA Replicates Take a look at this short video clip that demonstrates how the DNA molecule replicates. A Science Odyssey :You Try It: DNA Workshop When you get to this website, click on \\"Go directly to the DNA Workshop\\". Click on DNA replication on the left ...

  15. Genetics

    NSDL National Science Digital Library

    The Tech Museum of Innovation

    2004-01-01

    This online tutorial from the TheTech Museum of Innovation focuses on genetics. The interactive topics will initially introduce the user to the DNA, chromosomes, and the make up of human genes. Further topics will examine forensic science, the history of forensics, fingerprinting, and cloning background research and community response to cloning. Finally, the resource provides connections to gallery exhibits, science labs, and a design challenge that engages the learner to write a persuasive letter to a group or organization responsible for cloning or DNA decision making. Copyright 2005 International Technology Education Association

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

    PubMed

    Mao, Gang; Liu, Lei

    2014-12-01

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

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

    PubMed Central

    MAO, GANG; LIU, LEI

    2014-01-01

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

  18. 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

  19. Complex multi-block analysis identifies new immunologic and genetic disease progression patterns associated with the residual ?-cell function 1 year after diagnosis of type 1 diabetes.

    PubMed

    Andersen, Marie Louise Max; Rasmussen, Morten Arendt; Pörksen, Sven; Svensson, Jannet; Vikre-Jørgensen, Jennifer; Thomsen, Jane; Hertel, Niels Thomas; Johannesen, Jesper; Pociot, Flemming; Petersen, Jacob Sten; Hansen, Lars; Mortensen, Henrik Bindesbøl; Nielsen, Lotte Brøndum

    2013-01-01

    The purpose of the present study is to explore the progression of type 1 diabetes (T1D) in Danish children 12 months after diagnosis using Latent Factor Modelling. We include three data blocks of dynamic paraclinical biomarkers, baseline clinical characteristics and genetic profiles of diabetes related SNPs in the analyses. This method identified a model explaining 21.6% of the total variation in the data set. The model consists of two components: (1) A pattern of declining residual ?-cell function positively associated with young age, presence of diabetic ketoacidosis and long duration of disease symptoms (P?=?0.0004), and with risk alleles of WFS1, CDKN2A/2B and RNLS (P?=?0.006). (2) A second pattern of high ZnT8 autoantibody levels and low postprandial glucagon levels associated with risk alleles of IFIH1, TCF2, TAF5L, IL2RA and PTPN2 and protective alleles of ERBB3 gene (P?=?0.0005). These results demonstrate that Latent Factor Modelling can identify associating patterns in clinical prospective data--future functional studies will be needed to clarify the relevance of these patterns. PMID:23755131

  20. 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 ...

  1. Genetics Home Reference: Erythromelalgia

    MedlinePLUS

    ... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Erythromelalgia On this page: Description Genetic changes Inheritance Diagnosis ... names Glossary definitions Reviewed November 2012 What is erythromelalgia? Erythromelalgia is a condition characterized by episodes of ...

  2. Genomic medicine for cancer diagnosis.

    PubMed

    Gordon, Benjamin L; Finnerty, Brendan M; Aronova, Anna; Fahey, Thomas J

    2015-01-01

    Genomic diagnostics in cancer has evolved since the completion of the Human Genome Project and the advancements made in diagnosis and therapy in chronic myelogenous leukemia. Among the diseases to achieve limited success or potentially benefit from diagnostic genetic testing are thyroid cancer, Burkitt's lymphoma, gastrointestinal stromal tumors, adrenocortical carcinoma, and colorectal cancer. With increased understanding of genomics, genetic tests should improve diagnosis and help guide medical and surgical management. PMID:25346009

  3. Learning about Tay-Sachs Disease

    MedlinePLUS

    ... Sandhoff Disease) HSCT for High Risk Inherited Inborn Errors Concurrent Single Gene and 24 Chromosome Aneuploidy Preimplantation Genetic Diagnosis (PGD) Current NHGRI Clinical Studies Search ClinicalTrials.gov [ ...

  4. MYH-Associated Polyposis

    MedlinePLUS

    ... increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done ... a complex procedure with financial, physical, and emotional factors for couples to consider before starting. For more ...

  5. Hereditary Papillary Renal Cell Carcinoma

    MedlinePLUS

    ... increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done ... a complex procedure with financial, physical, and emotional factors for couples to consider before starting. For more ...

  6. Muir-Torre Syndrome

    MedlinePLUS

    ... increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done ... a complex procedure with financial, physical, and emotional factors for couples to consider before starting. For more ...

  7. 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.

  8. Importance of genetic diversity assessment in crop plants and its recent advances: an overview of its analytical perspectives.

    PubMed

    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

  9. Genetic screening of a pedigree with osteogenesis imperfecta type ? and identification of a novel mutation in COL1A2 pathogenic gene.

    PubMed

    Rong, Li; Yuanping, Guo; Jingxin, Pan; Yibin, Guo

    2015-01-01

    To uncover the molecular pathogenic mechanism of congenital osteogenesis imperfecta (OI) type I, all the 103 exons of the COL1A1 (Collagen, type ?, alpha 1) and COL1A2 (Collagen, type ?, alpha 2) genes in a child with OI type ? were screened using PCR-DNA direct sequencing. The results showed no pathological mutation in COL1A1 gene, but a novel mutation c.946G>T/p.G316C in the exon 19 of COL1A2 gene, which was inherited from her father. This mutation was not found in her mother and other six phenotypically normal relatives. By denaturing high performance liquid chromatography (DHPLC) screening, the abnormal double-peak was visualized in PCR products of exon 19 of COL1A2 gene in the proband and her father, while the normal single-peak was shown in those of her mother and all the healthy controls. Using allele specific amplification (ASA) screening, a specific band of 391 bp in COL1A2 exon 19 was amplified only in the proband and her father, but not in other samples. The amino acid encoded by the mutation site is evolutionarily highly conserved, and this mutation was a "damaging" or "probably damaging" factor to OI type ?, based on the predicting results using SIFT and Polyphen-2 softwares. In conclusion, the novel c.946G>T/p.G316C mutation in COL1A2 gene is a pathogenic mutation that could result in OI type ?. If the couple wants to get pregnant again, it is necessary to screen the mutation site in COL1A2 gene through the prenatal genetic diagnosis in the first trimester or through preimplantation genetic diagnosis (PGD) in the progestation. PMID:25608812

  10. Scabies Diagnosis

    MedlinePLUS

    ... message, please visit this page: About CDC.gov . Parasites - Scabies Parasites Home Share Compartir Diagnosis Diagnosis of a scabies ... Cases Publications Information For: Institutions Travelers Related Links Parasites A-Z Index Parasites Glossary Neglected Tropical Diseases ...

  11. Genetic variants in telomerase-related genes are associated with an older age at diagnosis in glioma patients: evidence for distinct pathways of gliomagenesis

    PubMed Central

    Walsh, Kyle M.; Rice, Terri; Decker, Paul A.; Kosel, Matthew L.; Kollmeyer, Thomas; Hansen, Helen M.; Zheng, Shichun; McCoy, Lucie S.; Bracci, Paige M.; Anderson, Erik; Hsuang, George; Wiemels, Joe L.; Pico, Alexander R.; Smirnov, Ivan; Molinaro, Annette M.; Tihan, Tarik; Berger, Mitchell S.; Chang, Susan M.; Prados, Michael D.; Lachance, Daniel H.; Sicotte, Hugues; Eckel-Passow, Jeanette E.; Wiencke, John K.; Jenkins, Robert B.; Wrensch, Margaret R.

    2013-01-01

    Background Genome-wide association studies have implicated single nucleotide polymorphisms (SNPs) in 7 genes as glioma risk factors, including 2 (TERT, RTEL1) involved in telomerase structure/function. We examined associations of these 7 established glioma risk loci with age at diagnosis among patients with glioma. Methods SNP genotype data were available for 2286 Caucasian glioma patients from the University of California, San Francisco (n = 1434) and the Mayo Clinic (n = 852). Regression analyses were performed to test for associations between “number of risk alleles” and “age at diagnosis,” adjusted for sex and study site and stratified by tumor grade/histology where appropriate. Results Four SNPs were significantly associated with age at diagnosis. Carrying a greater number of risk alleles at rs55705857 (CCDC26) and at rs498872 (PHLDB1) was associated with younger age at diagnosis (P = 1.4 × 10?22 and P = 9.5 × 10?7, respectively). These SNPs are stronger risk factors for oligodendroglial tumors, which tend to occur in younger patients, and their association with age at diagnosis varied across tumor subtypes. In contrast, carrying more risk alleles at rs2736100 (TERT) and at rs6010620 (RTEL1) was associated with older age at diagnosis (P = 6.2 × 10?4 and P = 2.5 × 10?4, respectively). These SNPs are risk factors for all glioma grades/histologies, and their association with age at diagnosis was consistent across tumor subgroups. Conclusions Carrying a greater number of risk alleles might be expected to decrease age at diagnosis. However, glioma susceptibility conferred by variation in telomerase-related genes did not follow this pattern. This supports the hypothesis that telomerase-related mechanisms of telomere maintenance are more associated with gliomas that develop later in life than those utilizing telomerase-independent mechanisms (ie, alternative lengthening of telomeres). PMID:23733245

  12. Genetics Home Reference: Tourette syndrome

    MedlinePLUS

    ... a variety of genetic and environmental factors, not changes in a single gene. Where can I find information about diagnosis or management of Tourette syndrome? These resources address the diagnosis ...

  13. Genetics of familial hypercholesterolemia.

    PubMed

    Brautbar, Ariel; Leary, Emili; Rasmussen, Kristen; Wilson, Don P; Steiner, Robert D; Virani, Salim

    2015-04-01

    Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein (LDL) cholesterol and premature cardiovascular disease, with a prevalence of approximately 1 in 200-500 for heterozygotes in North America and Europe. Monogenic FH is largely attributed to mutations in the LDLR, APOB, and PCSK9 genes. Differential diagnosis is critical to distinguish FH from conditions with phenotypically similar presentations to ensure appropriate therapeutic management and genetic counseling. Accurate diagnosis requires careful phenotyping based on clinical and biochemical presentation, validated by genetic testing. Recent investigations to discover additional genetic loci associated with extreme hypercholesterolemia using known FH families and population studies have met with limited success. Here, we provide a brief overview of the genetic determinants, differential diagnosis, genetic testing, and counseling of FH genetics. PMID:25712136

  14. Genetics Home Reference: Moebius syndrome

    MedlinePLUS

    ... Moebius syndrome? These resources address the diagnosis or management of Moebius syndrome and may include treatment providers. Boston Children's Hospital Cleveland Clinic Genetic Testing Registry: Oromandibular-limb ...

  15. Diamond Blackfan Anemia, Genetics, and You

    MedlinePLUS

    ... the causes of the disorder. Q What is genetic testing? A Genetic testing is typically done to check for mutations or ... rule out or confirm a diagnosis. Q Can genetic testing be used to detect DBA mutations? A Yes, ...

  16. 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 ...

  17. Genetics Home Reference: Polycythemia vera

    MedlinePLUS

    ... Recent literature OMIM Genetic disorder catalog Conditions > Polycythemia vera On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed July 2013 What is polycythemia vera? Polycythemia vera is a condition characterized by an ...

  18. 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 May 2006 What is congenital hypothyroidism? Congenital hypothyroidism is a condition that affects infants ...

  19. 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 Home Health Handbook: Dermatitis ...

  20. 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 July 2009 What is beta thalassemia? Beta thalassemia is a blood disorder that reduces ...

  1. Genetics Home Reference: Alpha thalassemia

    MedlinePLUS

    ... Recent literature OMIM Genetic disorder catalog Conditions > Alpha thalassemia On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed August 2009 What is alpha thalassemia? Alpha thalassemia is a blood disorder that reduces ...

  2. Inconclusive TSC Genetic Test Results

    MedlinePLUS

    ... TEST RESULTS Download a PDF of this information. Genetic testing for tuberous sclerosis complex (TSC) has been routinely ... their or their child’s diagnosis of TSC. However, genetic testing cannot always give you a “yes or no” ...

  3. 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 ...

  4. Arlequin based PGD domain decomposition

    NASA Astrophysics Data System (ADS)

    Nazeer, S. Mohamed; Bordeu, Felipe; Leygue, Adrien; Chinesta, Francisco

    2014-11-01

    Problems defined in fully or partially separable domains can be solved by considering a space separated representation of the unknown fields. Thus three-dimensional problems can be solved from the solution of some one-dimensional problems in the case of fully separated representations involving the three space coordinates or as a sequence of 2D and 1D problems in the case of partially separated representations (plates, shells or extruded geometries). When the domains become more complex, sometimes they can be simplified by using appropriate mappings. When it is not possible or such a transformation becomes too complex, the use of domain decomposition could facilitate the use of separated representations. However, domain coupling in the context of space separated representations have never been analyzed. In this paper we propose a domain decomposition strategy based on the use of space separated representations and the Arlequin coupling strategy. First we consider separated representations of the physical space that will be then extended to address parametric solutions.

  5. Regulation of Enzyme Activities in Drosophila: Genetic Variation Affecting Induction of Glucose 6-Phosphate and 6-Phosphogluconate Dehydrogenases in Larvae

    PubMed Central

    Cochrane, Bruce J.; Lucchesi, John C.; Laurie-Ahlberg, C. C.

    1983-01-01

    The genetic basis of modulation by dietary sucrose of the enzyme activities glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) activities in third instar larvae of Drosophila melanogaster was investigated, using isogenic lines derived from wild populations. Considerable genetically determined variation in response was detected among lines that differed only in their third chromosome constitution. Comparison of crossreacting material between a responding and a nonresponding line showed that the G6PD activity variation is due to changes in G6PD protein level. These differences in responses are localized in the fat body, with 300 m m sucrose in the diet resulting in a sixfold stimulation of G6PD activity and a fourfold one of 6PGD in the line showing the strongest response. In this tissue, the responses of the two enzymes are closely correlated with one another. Using recombinant lines, we obtained data that suggested the existence of more than one gene on chromosome III involved in the regulation of G6PD in the fat body, and at least one of these genes affects the level of 6PGD as well. PMID:6416921

  6. Techniques for Precancerous Lesion Diagnosis

    PubMed Central

    Mendes, Sarah Freygang; de Oliveira Ramos, Grasieli; Rivero, Elena Riet Correa; Modolo, Filipe; Grando, Liliane Janete; Meurer, Maria Inês

    2011-01-01

    The development of the oral squamous cell carcinoma (OSCC) is a multistep process that requires the accumulation of multiple genetic alterations usually preceded by detectable mucosal changes, most often leukoplakias and erythroplakias. The clinical appearance of oral precancerous lesions and their degree of epithelium dysplasia suggests the malignization potential. Several techniques have been developed to improve the clinical and cytological diagnosis of oral precancerous lesions. The present paper reviews the main techniques used to improve premalignant lesion diagnosis. PMID:21318165

  7. [Hypertrophic cardiomyopathy -- modern state of the problem. Issues of epidemiology and nomenclature, genetics and pathophysiology, variants of course and differential diagnosis].

    PubMed

    Belenkov, Iu N; Privalova, E V; Kaplunova, V Iu; Khabarova, N V; Shakar'iants, G A

    2013-01-01

    The problem of the study of hypertrophic cardiomyopathy (HCM) has preserved its actuality because of high prevalence (1:500), risk of sudden cardiac death (SCD) in individuals of young able-bodied age. Subject of great interest appear problems of search for additional clinical, instrumental and genetic markers, environmental factors which are capable to influence formation of a clinical variant of HCM course, risk of SCD, and prognosis of HCM. Important problem requiring further study appears to be molecular genetic characteristic of the disease. Integrated nomenclature of various forms and variants of course of HCM is essential for elaboration of tactics of management of patients and assessment of results of multicenter trials. PMID:23952988

  8. PRENATAL DIAGNOSIS Prenat Diagn (2011)

    E-print Network

    2011-01-01

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

  9. 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.

  10. 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.

  11. Genetic Stroke Syndromes

    PubMed Central

    Barrett, Kevin M.; Meschia, James F.

    2014-01-01

    Purpose of Review: This review describes the clinical and radiographic features, genetic determinants, and treatment options for the most well-characterized monogenic disorders associated with stroke. Recent Findings: Stroke is a phenotype of many clinically important inherited disorders. Recognition of the clinical manifestations of genetic disorders associated with stroke is important for accurate diagnosis and prognosis. Genetic studies have led to the discovery of specific mutations associated with the clinical phenotypes of many inherited stroke syndromes. Summary: Several inherited causes of stroke have established and effective therapies, further underscoring the importance of timely diagnosis. PMID:24699489

  12. Association between Genetic Variation in the Oxytocin Receptor Gene and Emotional Withdrawal, but not between Oxytocin Pathway Genes and Diagnosis in Psychotic Disorders

    PubMed Central

    Haram, Marit; Tesli, Martin; Bettella, Francesco; Djurovic, Srdjan; Andreassen, Ole Andreas; Melle, Ingrid

    2015-01-01

    Social dysfunction is common in patients with psychotic disorders. Oxytocin is a neuropeptide with a central role in social behavior. This study aims to explore the relationship between oxytocin pathway genes and symptoms related to social dysfunction in patients with psychotic disorders. We performed association analyses between four oxytocin pathway genes (OXT, OXTR, AVP, and CD38) and four areas of social behavior-related psychopathology as measured by Positive and Negative Syndrome Scale. For this purpose, we used both a polygenic risk score (PGRS) and single OXTR candidate single nucleotide polymorphism previously reported in the literature (rs53576, rs237902, and rs2254298). A total of 734 subjects with DSM-IV psychotic spectrum disorders and 420 healthy controls were included. Oxytocin pathway PGRSs were calculated based on the independent Psychiatric Genomics Consortium study sample. There was a significant association between symptom of Emotional Withdrawal and the previously reported OXTR risk allele A in rs53576. No significant associations between oxytocin pathway gene variants and a diagnosis of psychotic disorder were found. Our findings indicate that while oxytocin pathway genes do not appear to contribute to the susceptibility to psychotic disorders, variations in the OXTR gene might play a role in the development of impaired social behavior. PMID:25667571

  13. Dual Diagnosis

    Microsoft Academic Search

    Mark S. Gold

    2005-01-01

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

  14. Genetics Home Reference: Duchenne and Becker muscular dystrophy

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Duchenne and Becker muscular dystrophy On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed February 2012 What is Duchenne and Becker muscular dystrophy? Muscular dystrophies are a group of genetic conditions ...

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

    PubMed

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

    2014-06-01

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

  16. Genetics Home Reference: Spastic paraplegia type 11

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Spastic paraplegia type 11 On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed April 2009 What is spastic paraplegia type 11? Spastic paraplegia type 11 is part of a ...

  17. Genetics Home Reference: Familial hemiplegic migraine

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > Familial hemiplegic migraine On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed January 2014 What is familial hemiplegic migraine? Familial hemiplegic migraine is a form of migraine ...

  18. 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 ...

  19. Genetics Home Reference: Atelosteogenesis type 3

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > Atelosteogenesis type 3 On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed September 2011 What is atelosteogenesis type 3? Atelosteogenesis type 3 is a disorder that affects ...

  20. 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 June 2012 What is intrahepatic cholestasis of pregnancy? Intrahepatic cholestasis of pregnancy is a liver disorder ...

  1. Genetics Home Reference: Congenital insensitivity to pain

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Congenital insensitivity to pain On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed November 2012 What is congenital insensitivity to pain? Congenital insensitivity to pain is a condition that ...

  2. Genetics Home Reference: Otopalatodigital syndrome type 1

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Otopalatodigital syndrome type 1 On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed November 2007 What is otopalatodigital syndrome type 1? Otopalatodigital syndrome type 1 is a disorder primarily ...

  3. Genetics Home Reference: Familial Mediterranean fever

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > Familial Mediterranean fever On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed June 2014 What is familial Mediterranean fever? Familial Mediterranean fever is an inherited condition characterized ...

  4. 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 October 2010 What is idiopathic pulmonary fibrosis? Idiopathic pulmonary fibrosis is a chronic, progressive lung ...

  5. Genetics Home Reference: Isolated Pierre Robin sequence

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Isolated Pierre Robin sequence On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed August 2013 What is isolated Pierre Robin sequence? Pierre Robin sequence is a set of abnormalities ...

  6. Endemic avian toxoplasmosis on a farm in Illinois: clinical disease, diagnosis, biologic and genetic characteristics of Toxoplasma gondii isolates from chickens (Gallus domesticus), and a goose (Anser anser).

    PubMed

    Dubey, J P; Webb, D M; Sundar, N; Velmurugan, G V; Bandini, L A; Kwok, O C H; Su, C

    2007-09-30

    Clinical toxoplasmosis in chickens (Gallus domesticus) has been rarely reported in literature. Here we report that three chickens on a farm in Illinois developed neurological signs. One of these chickens was examined postmortem and it had non-suppurative encephalitis with numerous Toxoplasma gondii tachyzoites and tissue cysts. The identity of the protozoa was confirmed immunohistochemically by staining with T. gondii specific antibodies, and by transmission electron microscopy. The owner of the 3 chickens donated all 11 remaining chickens and a goose on his property for the present study. All 11 chickens and a goose were euthanized, and blood, heart, brain, and 1 leg were obtained for T. gondii examination. Antibodies to T. gondii were found in sera of all chickens with titers of 1:40 in one, 1:320 in three, and 1:640 or higher in seven chickens tested by the modified agglutination test (MAT). The goose had a MAT titer of 1:320. For isolation of T. gondii, whole heart and brain and 50 g of leg muscles were digested in an acid-pepsin solution and bioassayed in four mice for each tissue. Viable T. gondii was isolated from tissues of all 11 chickens and the goose. Genotyping of these 12 T. gondii isolates using polymorphism at the genetic loci SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, a new SAG2 and Apico revealed that all isolates had Type II alleles at all loci, indicating these T. gondii isolates belong to the predominant clonal Type II lineages. This is the first report of isolation of viable T. gondii from a domestic goose (Anser anser). PMID:17656021

  7. 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.

  8. Diagnosis and prevention of thalassemia.

    PubMed

    Ip, Ho-Wan; So, Chi-Chiu

    2013-11-01

    Thalassemia is the most common monogenic inherited disease worldwide and it affects most countries to various extents. This review summarizes the current approaches to phenotypic and genotypic diagnosis of thalassemia in clinical practice. Prevention strategies that encompass carrier screening, genetic counseling and prenatal diagnosis are discussed. The importance of public education and an awareness of a changing perception regarding this group of diseases are emphasized. It also addresses the impact of the rapidly increasing knowledge in disease severity modification by hemoglobin F (Hb F). PMID:24295057

  9. 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, allergies, medications, and the results of any medical or ...

  10. Genetics of anxiety disorders

    Microsoft Academic Search

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

    2004-01-01

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

  11. Better diagnosis, David BotsteinSite: DNA Interactive (www.dnai.org)

    NSDL National Science Digital Library

    2008-03-26

    Interviewee: David Botstein DNAi Location:Applications>Genes and medicine>Genetic profiling>David Botstein Better diagnosis David Botstein talks about the goal of using microarray analysis to improve cancer diagnosis.

  12. Prenatal diagnosis of congenital anomalies

    PubMed Central

    Todros, T; Capuzzo, E; Gaglioti, P

    2001-01-01

    Up till the early 1970s, prenatal diagnosis of congenital anomalies was primarily aimed at detecting chromosomal abnormalities by amniocentesis.1. Over the last two decades, prenatal diagnosis has greatly benefited from advances in ultrasound technology and in our ability to detect microscopic and submicroscopic chromosome abnormalities as well as single gene disorders, leading to substantive improvements in detection of such congenital anomalies.2 At present, invasive prenatal diagnosis continues to be the gold standard for pregnancies at increased risk for chromosomal anomaly or other genetic disease, with chorionic villus sampling being the procedure of choice for the first trimester,3 whereas mid-trimester amniocentesis continues to be the most common form of invasive procedure for prenatal diagnosis.4 Still, invasive techniques are restricted to subgroups at risk for anomalies, for whom such time-consuming procedures are believed to be cost-effective, also accounting for procedure-related abortive risks. In the low-risk population prenatal diagnosis generally consists of screening procedures by means of ultrasound and maternal serum biochemistry. PMID:22368596

  13. Wavelets meet genetic imaging

    NASA Astrophysics Data System (ADS)

    Wang, Yu-Ping

    2005-08-01

    Genetic image analysis is an interdisciplinary area, which combines microscope image processing techniques with the use of biochemical probes for the detection of genetic aberrations responsible for cancers and genetic diseases. Recent years have witnessed parallel and significant progress in both image processing and genetics. On one hand, revolutionary multiscale wavelet techniques have been developed in signal processing and applied mathematics in the last decade, providing sophisticated tools for genetic image analysis. On the other hand, reaping the fruit of genome sequencing, high resolution genetic probes have been developed to facilitate accurate detection of subtle and cryptic genetic aberrations. In the meantime, however, they bring about computational challenges for image analysis. In this paper, we review the fruitful interaction between wavelets and genetic imaging. We show how wavelets offer a perfect tool to address a variety of chromosome image analysis problems. In fact, the same word "subband" has been used in the nomenclature of cytogenetics to describe the multiresolution banding structure of the chromosome, even before its appearance in the wavelet literature. The application of wavelets to chromosome analysis holds great promise in addressing several computational challenges in genetics. A variety of real world examples such as the chromosome image enhancement, compression, registration and classification will be demonstrated. These examples are drawn from fluorescence in situ hybridization (FISH) and microarray (gene chip) imaging experiments, which indicate the impact of wavelets on the diagnosis, treatments and prognosis of cancers and genetic diseases.

  14. Genetic Technologies and Ethics

    Microsoft Academic Search

    Ali M. Ardekani

    In the past decade, the human genome has been completely sequenced and the know- ledge 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

  15. Imaging genetics—days of future past

    Microsoft Academic Search

    Kristin L. Bigos; Daniel R. Weinberger

    2010-01-01

    Imaging genetics provides a unique tool with which to explore and evaluate the functional impact of brain-relevant genetic polymorphisms with the potential to understand their impact on behavior. Because statistical association with clinical diagnosis does not establish biological significance nor identify a mechanism of risk, imaging genetics is a uniquely valuable strategy for extending statistical evidence with biological data. Applications

  16. Genetics of hepatobiliary carcinogenesis.

    PubMed

    Nault, Jean-Charles; Zucman-Rossi, Jessica

    2011-05-01

    Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are two leading causes of cancer death in the world. Liver carcinogenesis is driven by genetic alterations in combination with viral and environmental factors. ?-catenin and P53 mutations represent the two main genetic alterations described in HCC, and P53 and KRAS mutations in CC, but rare genetic alterations could be particularly valuable if they constitute drug-able targets (such as PIK3CA or EGFR mutations). Recent progress using global genomic analysis has highlighted the marked genetic heterogeneity of this disease and this approach has also been used to assess prognosis or refine the diagnosis. The validation of sorafenib as the first targeted therapy useful in HCC has opened up new prospects for biotherapy in this cancer. In the future, mapping of genetic alterations will be essential to adapt treatment to HCC and CC biology. PMID:21538283

  17. [Basic aspects of medical genetics].

    PubMed

    Pajarola, Sandra; Bachmann, Ruxandra; Niedrist, Dunja; Rauch, Anita

    2013-11-27

    The human genome consists of 23 pairs of chromosomes that contain 20 000-25 000 genes. Genetic disorders can be caused by different mechanisms, and therefore the confirmation of a suspected diagnosis requires knowledge of the underlying defect, so that the correct test can be applied. Monogenic diseases are caused by disturbances in a single gene, and currently only targeted diagnostic testing is available following a specific clinical suspicion. Chromosomal disorders usually involve multiple genes, so that the symptoms are often less specific. Specialists in Medical Genetics FMH are trained in creating a clinical genetic differential diagnosis, requesting the according laboratory test, interpretating the results and providing expert genetic counseling in presymptomatic and prenatal diagnosis. In Switzerland, specific legal principles and ethical guidelines must be taken into account. PMID:24280602

  18. [Genetic analysis].

    PubMed

    Morishita, Eriko

    2014-07-01

    Deficiencies of natural anticoagulant proteins including antithrombin (AT), protein C (PC) and protein S (PS) are important risk factors for venous thromboembolism (VTE) in Japanese people. The identification of deficiencies of these proteins is important for the prevention and treatment of VTE. Genetic analysis can help in making a definitive diagnosis of these inherited deficiencies, and can be useful both for the individual and potential thrombotic risk to family members. Mutations of AT, PC and PS are usually detected by direct DNA sequencing and multiple ligation-dependent probe amplification (MLPA). Large cohort studies have shown that AT and PC mutations are identified in 85% and 70% of patients, respectively. On the other hand, the detection rate in PS deficiency is lower in around 40% of patients. PMID:25163314

  19. Genetic diversity of cattle in south China as revealed by blood protein electrophoresis.

    PubMed

    Nie, L; Yu, Y; Zhang, X Q; Yang, G F; Wen, J K; Zhang, Y P

    1999-08-01

    Genetic variation of 31 blood protein loci in 236 cattle from eight South China populations (including mithan, Bos frontalis) and a Holstein population was investigated by means of horizontal starch gel electrophoresis. Thirteen loci (ALB, CAR, Hb-b, Np, PGM, Amy-I, PEP-B, AKP, 6PGD, Cp, Pa, EsD, and TF) were found to be polymorphic. The comparison of average heterozygosities (H) shows that all the native cattle embrace a rich genetic diversity. Our results on protein polymorphism suggest that cattle in China originated mainly from Bos indicus and Bos taurus; Xuwen, Hainan, Wenshan, and Dehong cattle and the Dehong zebu are close to zebu-type cattle, and Diqing and Zhaotong cattle are close to the taurine. The mithan was very different from other native cattle, and we suggest that its origin was complicated and may be influenced by other cattle species. PMID:10624516

  20. Human herpesvirus infections: Pathogenesis, diagnosis, and treatment

    SciTech Connect

    Lopez, C.; Roizman, B.

    1986-01-01

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

  1. Biological substrates underpinning diagnosis of major depression

    E-print Network

    Sibille, Etienne

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

  2. Prenatal Diagnosis of Fetal Brain Tumors

    Microsoft Academic Search

    Manuel Alvarez; Usha Chitkara; Lauren Lynch; Karen E. Mehalek; Debra Heller; Richard L. Berkowitz

    1987-01-01

    Two cases of congenital brain tumors were detected during routine antepartum sonography at the Mount Sinai Medical Center Perinatal Ultrasound Unit. In both cases, diagnosis was made during the third trimester at 31 and 33 weeks, respectively. In one of these patients, no intracranial abnormalities were noted on a sonogram performed in conjunction with genetic amniocentesis at 18 weeks gestation.

  3. Genetics Home Reference: Myostatin-related muscle hypertrophy

    MedlinePLUS

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

  4. Genetics Home Reference: GRN-related frontotemporal dementia

    MedlinePLUS

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

  5. Genetics Home Reference: Sensorineural deafness and male infertility

    MedlinePLUS

    ... Genetic disorder catalog Conditions > Sensorineural deafness and male infertility On this page: Description Genetic changes Inheritance Diagnosis ... April 2010 What is sensorineural deafness and male infertility? Sensorineural deafness and male infertility is a condition ...

  6. Genetics Home Reference: CATSPER1-related nonsyndromic male infertility

    MedlinePLUS

    ... Genetic disorder catalog Conditions > CATSPER1-related nonsyndromic male infertility On this page: Description Genetic changes Inheritance Diagnosis ... April 2010 What is CATSPER1-related nonsyndromic male infertility? CATSPER1 -related nonsyndromic male infertility is a condition ...

  7. Genetics in the art and art in genetics.

    PubMed

    Bukvic, Nenad; Elling, John W

    2015-01-15

    "Healing is best accomplished when art and science are conjoined, when body and spirit are probed together", says Bernard Lown, in his book "The Lost Art of Healing". Art has long been a witness to disease either through diseases which affected artists or diseases afflicting objects of their art. In particular, artists have often portrayed genetic disorders and malformations in their work. Sometimes genetic disorders have mystical significance; other times simply have intrinsic interest. Recognizing genetic disorders is also an art form. From the very beginning of my work as a Medical Geneticist I have composed personal "algorithms" to piece together evidence of genetics syndromes and diseases from the observable signs and symptoms. In this paper we apply some 'gestalt' Genetic Syndrome Diagnostic algorithms to virtual patients found in some art masterpieces. In some the diagnosis is clear and in others the artists' depiction only supports a speculative differential diagnosis. PMID:25089030

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

    E-print Network

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

  9. 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

  10. [Bioethics in genetic engineering].

    PubMed

    Gutiérrez-Samperio, César

    2002-01-01

    The advances in the field of molecular biology and genetics have widened the possibilities for the diagnosis and treatment of hereditary diseases. At the same time research into this field has broken bounds of its legal and ethical regulation. The intention of this paper is not to analyze these advances from scientific and technical point of view which is the area of the specialist, but rather to review historical antecedents of genetic engineering; the legal and ethical repercussions of the human genome project (HGP); in vitro fertilization and embryo transfer (FIVET); the embryo research which is being caused out and which may be possible; other fields of genetics and cloning especially germinal cells and human beings; genetic diagnosis and its family, social and work repercussions; treatment through genetic engineering, research into cloning in order to obtain organs and tissues for transplants; and the use of genetic engineering in the biomedical industry. To avoid these advances working against humans, the organization and participation of multidisciplinary bodies are required to provide legal and ethical supervision. PMID:11885124

  11. Genetic Counseling

    MedlinePLUS

    ... this page It's been added to your dashboard . Genetic counseling Genetic counseling is a service to help ... child care and genetic testing. Who should get genetic counseling? Anyone who has unanswered questions about origins ...

  12. 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

  13. Genetics for the ophthalmologist.

    PubMed

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

    2012-09-01

    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

  14. The genetics of paragangliomas.

    PubMed

    Burnichon, N; Abermil, N; Buffet, A; Favier, J; Gimenez-Roqueplo, A-P

    2012-12-01

    Over the last decade, it has been clearly established that one-third of all paragangliomas are genetically determined. Genetic testing, guided by the family history and clinical findings, must now be proposed to all subjects undergoing surgery for head and neck paraganglioma. When a mutation is identified on one of the susceptibility genes (SDHD, SDHB, SDHC, SDHAF2, VHL), at-risk subjects should be investigated for the presence of other supra- and infradiaphragmatic paragangliomas and functional catecholamine-secreting paragangliomas and/or phaeochromocytomas. Identification of a germline mutation on the SDHB gene is a high-risk factor for malignancy and poor prognosis and requires close surveillance of subjects carrying this mutation. The diagnosis of hereditary paraganglioma also allows predictive genetic screening in first-degree relatives of the index subject. Genetic testing for paraganglioma is therefore now an important component of the diagnostic and therapeutic management of these patients. PMID:23078982

  15. Reproductive decisions after fetal genetic counselling.

    PubMed

    Pergament, Eugene; Pergament, Deborah

    2012-10-01

    A broad range of testing modalities for fetal genetic disease has been established. These include carrier screening for single-gene mutations, first-trimester and second-trimester screening for chromosome abnormalities and open neural-tube defects, prenatal diagnosis by means of chorionic villus sampling and amniocentesis, and preimplantation genetic diagnosis. Reproductive decisions before and after fetal genetic counselling represent the culmination of a dynamic interaction between prospective parents, obstetrician and genetic counsellor. The decision to undergo genetic testing before and after genetic counselling is influenced by a host of interrelated factors, including patient-partner and family relationships, patient-physician communication, societal mores, religious beliefs, and the media. Because of the complexity of personal and societal factors involved, it is not surprising that genetic counselling concerning reproductive decision-making must be individualised. A limited number of principles, guidelines and standards apply when counselling about testing for fetal genetic disease. These principles are that genetic counselling should be non-directive and unbiased and that parental decisions should be supported regardless of the reproductive choice. A critical responsibility of the obstetrician and genetic counsellor is to provide accurate and objective information about the implications, advantages, disadvantages and consequences of any genetic testing applied to prospective parents and their fetuses. These principles and responsibilities will be tested as newer technologies, such as array comparative genome hybridisation, non-invasive prenatal diagnosis and sequencing of the entire genome are introduced into the field of reproductive genetics and become routine practice. PMID:22809468

  16. Genetic Diagnostic Methods for Inherited Eye Diseases

    PubMed Central

    Gabriel, Luis A. R.; Traboulsi, Elias I.

    2011-01-01

    Accurate molecular diagnosis of genetic eye diseases has proven to be of great importance because of the prognostic and therapeutic value of an accurate ascertainment of the underlying genetic mutation. Efforts continue in diagnostic laboratories to develop strategies that allow the discovery of responsible gene/mutations in the individual patient using the least number of assays and economizing on the expenses and time involved in the process. Once the ophthalmologist has made the best possible clinical diagnosis, blood samples are obtained for genetic testing. In this paper we will review the basic laboratory methods utilized to identify the chromosomal or mutational etiology of genetic diseases that affect the eye. PMID:21572730

  17. Genetic screening: The vista of genomic medicine

    PubMed Central

    Saini, Rajiv; Saini, Santosh; Saini, Gagan

    2011-01-01

    The accelerating development of biochemical and DNA-based diagnostic tests for human genetic conditions in the last decade has engendered a revolution in genetic diagnosis. Both genetic testing and genetic screening involve the same testing processes to examine an individual’s chromosomes, DNA, or the biochemical product of a gene, typically a protein to confirm or refute a suspected chromosomal, DNA, or gene product change. The identification of genetic disorders, and the potential for developing a therapy, is a powerful force in genetics and medicine. PMID:21430960

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

    PubMed

    Filippov, E G; Andronova, E V

    2011-05-01

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

  19. Genetics Home Reference: Gastrointestinal stromal tumor

    MedlinePLUS

    ... gastrointestinal stromal tumor and may include treatment providers. American Cancer Society: Treating Gastrointestinal Stromal Tumor (GIST) Cancer.Net: Gastrointestinal Stromal Tumor--Diagnosis Genetic Testing Registry: Gastrointestinal Stromal Tumors You might also find ...

  20. Genetics Home Reference: Juvenile primary osteoporosis

    MedlinePLUS

    ... Research studies PubMed Recent literature Conditions > Juvenile primary osteoporosis On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed January 2013 What is juvenile primary osteoporosis? Juvenile primary osteoporosis is a skeletal disorder characterized ...

  1. Genetics Home Reference: Sporadic hemiplegic migraine

    MedlinePLUS

    ... Research studies PubMed Recent literature Conditions > Sporadic hemiplegic migraine On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed February 2014 What is sporadic hemiplegic migraine? Sporadic hemiplegic migraine is a rare form of ...

  2. How Are Genetic Conditions Treated or Managed?

    MedlinePLUS

    ... trials. Find out more about the treatment and management of genetic conditions: Links to information about the ... Where can I find information about diagnosis or management of...?” GeneReviews , a resource from the University of ...

  3. 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 ...

  4. 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 ...

  5. 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 ...

  6. 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 ...

  7. [Genetics of hypophosphatasia].

    PubMed

    Mornet, E; Simon-Bouy, B

    2004-05-01

    Hypophosphatasia is a rare inherited disorder characterized by defective bone and teeth mineralization and deficiency of serum and bone alkaline phosphatase activity. The symptoms are highly variable in their clinical expression, which ranges from stillbirth without mineralized bone to early loss of teeth without bone symptoms. Currently, there is no treatment for the disease. Recent developments in molecular biology allow to better understand the genetics of the disease, especially its transmission that may be recessive or dominant, to improve genetic counseling and molecular diagnosis, and offer new perspectives of treatment. PMID:15135429

  8. Early diagnosis of Parkinson's disease.

    PubMed

    Becker, Georg; Müller, Antje; Braune, Stefan; Büttner, Thomas; Benecke, Reiner; Greulich, Wolfgang; Klein, Wolfgang; Mark, Günter; Rieke, Jürgen; Thümler, Reiner

    2002-10-01

    In idiopathic Parkinson's disease (IPD) approximately 60 % of the nigrostriatal neurons of the substantia nigra (SN) are degenerated before neurologists can establish the diagnosis according to the widely accepted clinical diagnostic criteria. It is conceivable that neuroprotective therapy starting at such an 'advanced stage' of the disease will fail to stop the degenerative process. Therefore, the identification of patients at risk and at earlier stages of the disease appears to be essential for any successful neuroprotection. The discovery of several genetic mutations associated with IPD raises the possibility that these, or other biomarkers, of the disease may help to identify persons at risk of IPD. Transcranial ultrasound have shown susceptibility factors for IPD related to an increased iron load of the substantia nigra. In the early clinical phase, a number of motor and particularly non-motor signs emerge, which can be identified by the patients and physicians years before the diagnosis is made, notably olfactory dysfunction, depression, or 'soft' motor signs such as changes in handwriting, speech or reduced ambulatory arm motion. These signs of the early, prediagnostic phase of IPD can be detected by inexpensive and easy-to-administer tests. As one single instrument will not be sensitive enough, a battery of tests has to be composed measuring independent parameters of the incipient disease. Subjects with abnormal findings in this test battery should than be submitted to nuclear medicine examinations to quantify the extent of dopaminergic injury and to reach the goal of a reliable, early diagnosis. PMID:12522572

  9. [Genetics of sudden unexplained death].

    PubMed

    Campuzano, Oscar; Allegue, Catarina; Brugada, Ramon

    2014-03-20

    Sudden unexplained death is defined by death without a conclusive diagnosis after autopsy and it is responsible for a large percentage of sudden deaths. The progressive interaction between genetics and forensics in post-mortem studies has identified inheritable alterations responsible for pathologies associated with arrhythmic sudden death. The genetic diagnosis of the deceased enables the undertaking of preventive measures in family members, many of them asymptomatic but at risk. The implications of this multidisciplinary translational medical approach are complex, requiring the dedication of a specialized team. PMID:24018251

  10. Macromelanosomes in the early diagnosis of neurofibromatosis.

    PubMed

    Slater, C; Hayes, M; Saxe, N; Temple-Camp, C; Beighton, P

    1986-08-01

    Skin biopsies of café-au-lait macules from 34 patients with a clinical diagnosis of classical neurofibromatosis were examined histologically and ultrastructurally to determine the presence or absence of macromelanosomes in the epidermal melanocytes and keratinocytes. Sixteen of the 34 patients had macromelanosomes. The presence of macromelanosomes varied with age and ethnic background; they were detected in nine of 12 Whites, six of 10 persons of mixed ancestry, and one of two Blacks. In these populations skin biopsy is useful in early diagnosis of neurofibromatosis. However, none of 10 persons of Indian stock had macromelanosomes. Their total absence in this group may be indicative of genetic heterogeneity. PMID:3094398

  11. [Genetics of ischemic stroke].

    PubMed

    Gschwendtner, A; Dichgans, M

    2013-02-01

    Stroke is one of the most widespread causes of mortality und disability worldwide. Around 80 % of strokes are ischemic and different forms of intracranial bleeding account for the remaining cases. Monogenic stroke disorders are rare but the diagnosis may lead to specific therapeutic consequences for the affected patients who are predominantly young. In common sporadic stroke, genetic factors play a role in the form of susceptibility genes. Their discovery may give rise to new therapeutic options in the future. PMID:23334453

  12. BREAST CANCER DETECTION USING GENETIC PROGRAMMING

    E-print Network

    Fernandez, Thomas

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

  13. Diagnosis and management of hereditary hemochromatosis.

    PubMed

    Salgia, Reena J; Brown, Kimberly

    2015-02-01

    Hereditary hemochromatosis is a rare genetic disorder that can have significant clinical consequences. Hemochromatosis is associated with iron overload, and can initially be recognized through laboratory testing for serum ferritin and transferrin saturation. Genetic testing for the HFE mutation can be performed in patients with elevated iron indices and a suspicion for hemochromatosis or liver disease. The main pathway resulting in iron overload is through altered hepcidin levels. Treatment of patients with the clinical phenotype of hereditary hemochromatosis is commonly through phlebotomy for removal of excess iron stores. This article highlights the current information and data regarding the diagnosis and management of hemochromatosis. PMID:25454304

  14. Designing babies: what the future holds

    Microsoft Academic Search

    Yury Verlinsky

    2005-01-01

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

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

    Microsoft Academic Search

    James M. Kauffman; Daniel P. Hallahan

    2009-01-01

    Ethical issues regarding children with disabilities have long involved their treatment after they are born. These issues remain important, but children may be deliberately created with or without characteristics that are usually thought of as disabilities. Preimplantation genetic diagnosis (PGD) and related technologies that involve human reproduction will become more readily available and raise new issues about the nature of

  16. Human embryonic stem cell lines derived from single blastomeres

    Microsoft Academic Search

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

    2006-01-01

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

  17. New Genetics

    MedlinePLUS

    ... Gene Editing with CRISPR Computing Genetics Model Organisms RNA Interference The New Genetics is a science education ... the basics of DNA and its molecular cousin RNA, and new directions in genetic research. The New ...

  18. Genetic counseling

    E-print Network

    Stough, Laura

    2014-01-01

    and susceptibility genes brought forth by the sequencing of the human genome has brought challenges to the field of genetic counseling. The traditional role of genetic counseling has significantly widened to address a diversity of developing needs, ranging from... GENETIC COUNSELING What Is Genetic Counseling? The National Society of Genetic Counselors (NSGC) defines genetic counseling as the process of assisting people with understanding and adapting to the medical, psychological, and familial implications...

  19. [Diagnosis and treatment of "acute psychosis" from the dimensional perspective].

    PubMed

    Harima, Hirohiko

    2011-01-01

    The term "acute psychosis" is commonly used as a provisional diagnosis in psychiatric acute settings, especially in emergency, when there is not sufficient information available to give a specific categorical diagnosis. The provisional diagnosis "acute psychosis" involves psychotic conditions with acute onset, psychotic conditions with unknown course and acute behavioural disorders with unknown subjective experiences. Because this provisional diagnosis is not a proper category, dimensional assessment of psychopathology including delusions, hallucinations, disorganization, mood/affect, catatonia and disorder of consciousness is required to start specific treatment. As "acute psychosis" is nosologically ill defined in the dichotomy of schizophrenia and mood disorder, traditional types such as bouffée délirante, cycloid psychoses and reactive psychosis are useful in practice as frames of reference. Because the provisional diagnosis of "acute psychosis" involves non-psychotic disorders such as adjustment disorders and personality disorders, the perspective of genetic understanding is helpful in making a non-dimensional differential diagnosis. PMID:22352008

  20. 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

  1. Genetic Counseling for Mental Health Disorders

    Microsoft Academic Search

    Elizabeth L. Pestka

    2005-01-01

    The sequenced map of the DNA base pairs in the human genome is making it easier to understand the biological pathways involved in mental illnesses and to develop better methods of diagnosis, treatment, and ultimately prevention. This article describes the genetic counseling process for psychiatric disorders, including the use of a family pedigree and predicting genetic inheritance risks based on

  2. Fragile XE: an important differential diagnosis

    PubMed Central

    Krishnan, Venkataraman; Clouston, Penny; Crocker, Mark; MacPherson, James; Heydon, Frances; Stewart, Helen

    2010-01-01

    Fragile X is a common cause of mental retardation in boys that can also affect girls. We present the case of a 21-year-old woman with Fragile X E (FRAXE) with learning difficulty, behavioural problems and epilepsy. Her diagnosis was made after investigations spanning several years, highlighting the importance of considering FRAXE and the benefits of reviewing genetic test results in the light of advancing technology. PMID:22442650

  3. An integrated diagnosis strategy for congenital myopathies.

    PubMed

    Böhm, Johann; Vasli, Nasim; Malfatti, Edoardo; Le Gras, Stéphanie; Feger, Claire; Jost, Bernard; Monnier, Nicole; Brocard, Julie; Karasoy, Hatice; Gérard, Marion; Walter, Maggie C; Reilich, Peter; Biancalana, Valérie; Kretz, Christine; Messaddeq, Nadia; Marty, Isabelle; Lunardi, Joël; Romero, Norma B; Laporte, Jocelyn

    2013-01-01

    Congenital myopathies are severe muscle disorders affecting adults as well as children in all populations. The diagnosis of congenital myopathies is constrained by strong clinical and genetic heterogeneity. Moreover, the majority of patients present with unspecific histological features, precluding purposive molecular diagnosis and demonstrating the need for an alternative and more efficient diagnostic approach. We used exome sequencing complemented by histological and ultrastructural analysis of muscle biopsies to identify the causative mutations in eight patients with clinically different skeletal muscle pathologies, ranging from a fatal neonatal myopathy to a mild and slowly progressive myopathy with adult onset. We identified RYR1 (ryanodine receptor) mutations in six patients and NEB (nebulin) mutations in two patients. We found novel missense and nonsense mutations, unraveled small insertions/deletions and confirmed their impact on splicing and mRNA/protein stability. Histological and ultrastructural findings of the muscle biopsies of the patients validated the exome sequencing results. We provide the evidence that an integrated strategy combining exome sequencing with clinical and histopathological investigations overcomes the limitations of the individual approaches to allow a fast and efficient diagnosis, accelerating the patient's access to a better healthcare and disease management. This is of particular interest for the diagnosis of congenital myopathies, which involve very large genes like RYR1 and NEB as well as genetic and phenotypic heterogeneity. PMID:23826317

  4. Enterobiasis (Pinworm Infection): Diagnosis

    MedlinePLUS

    ... General Information Pinworm Infection FAQs Epidemiology & Risk Factors Biology Disease Diagnosis Treatment Prevention & Control Resources for Health Professionals Publications Information For: Travelers ...

  5. Ethical dilemmas in clinical genetics.

    PubMed Central

    Young, I D

    1984-01-01

    This paper discusses the results of a survey of medical and paramedical opinion relating to various difficult ethical issues in clinical genetics. These include the confidentiality of the doctor-patient relationship, prenatal diagnosis and termination, and Huntington's chorea. It is suggested that this method provides a useful means of assessing what is ethically acceptable in contemporary society. PMID:6234396

  6. First trimester prenatal diagnosis: amniocentesis.

    PubMed

    Delisle, M F; Wilson, R D

    1999-10-01

    Twenty years after midtrimester genetic amniocentesis was first used, first trimester invasive prenatal procedures were introduced. Chorionic villous sampling presents some disadvantages that entitled many centers to look into an alternative for first trimester diagnosis. Early amniocentesis (EA) can be performed effectively, as shown over the years in many observational studies and partially randomized and randomized trials. Recently, a multicenter randomized trial (Canadian Early and Midtrimester Amniocentesis Trial) reported a higher total pregnancy loss, a significant increased incidence of musculoskeletal foot deformities, a significant increased culture failure rate, and an increased postamniocentesis rate of leakage in the EA group compared with midtrimester amniocentesis. These results concerning EA procedures from 11w(+0) to 12w(+6) should be included in any pre-EA counseling. However, further trials have started to evaluate EA procedures between 13w(+0) to 14w(+6). PMID:10551794

  7. Mendelian Genetics

    NSDL National Science Digital Library

    Phillip McClean

    2000-01-01

    Comprehensive presentation of Mendelian genetics enhanced with schematic diagrams and color photos. A sidebar of topics includes Variations to Mendel's First Law, Pedigree Analysis, Mendel's Second Law, Pleiotropy, Epistasis, Modifier Genes, Penetrance and Expressivity, Study Questions, Mendelian Genetics Overheads, Mendelian Genetics WWW Links Genetic Topics

  8. A generic, flexible protocol for preimplantation human leukocyte antigen typing alone or in combination with a monogenic disease, for rapid case work-up and application.

    PubMed

    Kakourou, Georgia; Destouni, Aspasia; Vrettou, Christina; Traeger-Synodinos, Jan; Kanavakis, Emmanuel

    2014-01-01

    Human leukocyte antigen (HLA) typing of in vitro fertilization (IVF) embryos, aims to establish a pregnancy that is HLA compatible with an affected sibling who requires hematopoietic stem cell transplantation (HSCT). It can be performed with or without preimplantation genetic diagnosis (PGD) for exclusion of a single-gene disorder (SGD) and it is a multistep, technically challenging procedure at every stage. Our purpose was to address the difficulties of genetic analysis by developing a fast, reliable and accurate PGD-HLA protocol, to simplify patient work-up and PGD application, while providing high flexibility for combination with any SGD. Requests included PGD-HLA for ?-thalassemia (?-thal)/sickle cell disease (most common request), Diamond-Blackfan anemia (DBA), chronic granulomatous disease (CGD) and preimplantation-HLA typing only. For HLA haplotyping, we selected a panel of 26 short tandem repeats (STRs) distributed across the entire HLA locus, following PGD guidelines. When required, mutation detection was performed by both a direct and indirect approach. To support concurrent SGD exclusion and HLA typing, a one-step, single-tube, multiplex fluorescent touchdown-polymerase chain reaction (PCR) was optimized. The described touchdown-PCR was successfully applied for all PGD-HLA protocols. Eight clinical cycles were performed with a diagnosis achieved for 94.7% of amplified biopsied blastomeres. Embryo transfer took place in six cycles, with two pregnancies achieved and two healthy female infants (from a twin pregnancy) born so far. Our protocol enables HLA typing in a single PCR, reducing the risk of contamination and the cost, and providing faster results. It requires minimum optimization before clinical application, irrespective of the SGD involved, decreasing the waiting time from referral to treatment for all PGD-HLA cases. PMID:24131134

  9. Genetics of Childhood Onset Schizophrenia

    PubMed Central

    Asarnow, Robert F; Forsyth, Jennifer K

    2014-01-01

    Synopsis Schizophrenia is a highly heritable disorder. The genetic architecture of schizophrenia is complex and heterogeneous involving both common and rare allelic variants. Given the low prevalence of childhood-onset schizophrenia (COS), relatively few studies have examined the genetic architecture of COS. This review discusses genetic studies of COS and compares findings in familial aggregation, common allele and rare allele studies of COS to those for adult onset schizophrenia (AOS). Overall, the extant literature suggests that COS is a rare variant of AOS with greater familial aggregation of schizophrenia spectrum disorders and a higher occurrence of rare allelic variants. Given the complex genetic architecture of schizophrenia, the utility of genetic screening for diagnosis and individualized treatment is currently limited; however, identifying common pathways through which multiple genes adversely impact neural systems offers great promise towards developing novel pharmacologic interventions. PMID:24012080

  10. Laboratory diagnosis of primary immunodeficiencies.

    PubMed

    Locke, Bradley A; Dasu, Trivikram; Verbsky, James W

    2014-04-01

    Primary immune deficiency disorders represent a highly heterogeneous group of disorders with an increased propensity to infections and other immune complications. A careful history to delineate the pattern of infectious organisms and other complications is important to guide the workup of these patients, but a focused laboratory evaluation is essential to the diagnosis of an underlying primary immunodeficiency. Initial workup of suspected immune deficiencies should include complete blood counts and serologic tests of immunoglobulin levels, vaccine titers, and complement levels, but these tests are often insufficient to make a diagnosis. Recent advancements in the understanding of the immune system have led to the development of novel immunologic assays to aid in the diagnosis of these disorders. Classically utilized to enumerate lymphocyte subsets, flow cytometric-based assays are increasingly utilized to test immune cell function (e.g., neutrophil oxidative burst, NK cytotoxicity), intracellular cytokine production (e.g., TH17 production), cellular signaling pathways (e.g., phosphor-STAT analysis), and protein expression (e.g., BTK, Foxp3). Genetic testing has similarly expanded greatly as more primary immune deficiencies are defined, and the use of mass sequencing technologies is leading to the identification of novel disorders. In order to utilize these complex assays in clinical care, one must have a firm understanding of the immunologic assay, how the results are interpreted, pitfalls in the assays, and how the test affects treatment decisions. This article will provide a systematic approach of the evaluation of a suspected primary immunodeficiency, as well as provide a comprehensive list of testing options and their results in the context of various disease processes. PMID:24569953

  11. 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

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

    E-print Network

    Stephens, Matthew

    During the course of the Medical Genetics residency training program, each trainee must acquire to the specialty of medical genetics, genetic counseling, and preparing lectures and seminars to many different will cover general medical genetics, dysmorphology and teratology, prenatal diagnosis and screening

  13. Genetic modification and genetic determinism

    Microsoft Academic Search

    David B. Resnik; Daniel B. Vorhaus

    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

  14. Molecular diagnosis of onychomycosis.

    PubMed

    Petinataud, D; Berger, S; Contet-Audonneau, N; Machouart, M

    2014-12-01

    Onychomycosis is a frequent cause of nail infections due to dermatophytes. Molds and yeast may also be responsible of these pathologies. Antifungal treatments are frequently given without a mycological diagnosis, partly because of the requisite time for obtaining the biological results. The mycological diagnosis requires a direct microscopic examination and a culture in order to accurately identify the fungal genus and species. Nevertheless, this conventional diagnosis is often time consuming due to the delay of fungal cultures and presents disadvantages that make it not sufficient enough to give a precise and confident response to the clinicians. Therefore additional tests have been developed to help distinguish onychomycosis from other nail disorders. Among them, molecular biology techniques offer modern and rapid tools to improve traditional microbiological diagnosis. In this review, we first present the conventional diagnosis methods for onychomycosis and then we describe the main molecular biology tools and the currently available commercial kits that allow a rapid detection of the pathology. PMID:25458365

  15. Errors in prenatal diagnosis.

    PubMed

    Anumba, Dilly O C

    2013-08-01

    Prenatal screening and diagnosis are integral to antenatal care worldwide. Prospective parents are offered screening for common fetal chromosomal and structural congenital malformations. In most developed countries, prenatal screening is routinely offered in a package that includes ultrasound scan of the fetus and the assay in maternal blood of biochemical markers of aneuploidy. Mistakes can arise at any point of the care pathway for fetal screening and diagnosis, and may involve individual or corporate systemic or latent errors. Special clinical circumstances, such as maternal size, fetal position, and multiple pregnancy, contribute to the complexities of prenatal diagnosis and to the chance of error. Clinical interventions may lead to adverse outcomes not caused by operator error. In this review I discuss the scope of the errors in prenatal diagnosis, and highlight strategies for their prevention and diagnosis, as well as identify areas for further research and study to enhance patient safety. PMID:23725900

  16. Molecular diagnosis of chronic granulomatous disease

    PubMed Central

    Roos, D; Boer, M

    2014-01-01

    Patients with chronic granulomatous disease (CGD) suffer from recurrent, life-threatening bacterial and fungal infections of the skin, the airways, the lymph nodes, liver, brain and bones. Frequently found pathogens are Staphylococcus aureus, Aspergillus species, Klebsiella species, Burkholderia cepacia and Salmonella species. CGD is a rare (?1:250 000 births) disease caused by mutations in any one of the five components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. This enzyme generates superoxide and is essential for intracellular killing of pathogens by phagocytes. Molecular diagnosis of CGD involves measuring NADPH oxidase activity in phagocytes, measuring protein expression of NADPH oxidase components and mutation analysis of genes encoding these components. Residual oxidase activity is important to know for estimation of the clinical course and the chance of survival of the patient. Mutation analysis is mandatory for genetic counselling and prenatal diagnosis. This review summarizes the different assays available for the diagnosis of CGD, the precautions to be taken for correct measurements, the flow diagram to be followed, the assays for confirmation of the diagnosis and the determinations for carrier detection and prenatal diagnosis. PMID:24016250

  17. Molecular diagnosis of chronic granulomatous disease.

    PubMed

    Roos, D; de Boer, M

    2014-02-01

    Patients with chronic granulomatous disease (CGD) suffer from recurrent, life-threatening bacterial and fungal infections of the skin, the airways, the lymph nodes, liver, brain and bones. Frequently found pathogens are Staphylococcus aureus, Aspergillus species, Klebsiella species, Burkholderia cepacia and Salmonella species. CGD is a rare (?1:250?000 births) disease caused by mutations in any one of the five components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. This enzyme generates superoxide and is essential for intracellular killing of pathogens by phagocytes. Molecular diagnosis of CGD involves measuring NADPH oxidase activity in phagocytes, measuring protein expression of NADPH oxidase components and mutation analysis of genes encoding these components. Residual oxidase activity is important to know for estimation of the clinical course and the chance of survival of the patient. Mutation analysis is mandatory for genetic counselling and prenatal diagnosis. This review summarizes the different assays available for the diagnosis of CGD, the precautions to be taken for correct measurements, the flow diagram to be followed, the assays for confirmation of the diagnosis and the determinations for carrier detection and prenatal diagnosis. PMID:24016250

  18. Prenatal diagnosis and treatment of 21-hydroxylase deficiency.

    PubMed

    Forest, M G; David, M; Morel, Y

    1993-04-01

    Prenatal diagnosis of 21-hydroxylase deficiency, the most common cause of congenital adrenal hyperplasia (CAH), has benefited from the advances in endocrinologic and molecular genetic studies. In 1976, prenatal diagnosis of the disease was first attempted by measuring 17-hydroxyprogesterone in the amniotic fluid in the second trimester of pregnancy. Discovery of a close linkage between HLA and the disease gave a second approach for prenatal diagnosis, the latter being made by linkage study of the haplotypes of the index case in a given family. Diagnosis was later made directly by molecular biology. Currently, the studies of the C4-CYP21B gene locus by Southern blotting and the CYP21B gene mutations by PCR methods simplify the diagnostic procedure of an early and accurate prenatal diagnosis in the first trimester. In these conditions all families are now informative. Moreover, using a direct genetic analysis associated with the possibility of detecting the heterozygotes in a non-related CAH population, a prenatal diagnosis can be done in a family without a previously CAH affected child. From our results in a series of 274 pregnancies at risk for CAH in whom prenatal diagnosis has been made by these different approaches, it can be concluded that steroid analysis in the amniotic fluid is an accurate method but provides only a late (second trimester) diagnosis, while an early and accurate diagnosis now relies on adequate molecular genetic studies on chorion villus biopsies. In the aim to prevent the virilization of the external genitalia in CAH female fetuses, prenatal treatment was instituted in our group in 1979 by giving dexamethasone to the mother. This prenatal treatment appears safe for the fetus and the child and is effective in preventing virilization of CAH affected females. Although the degree of prevention is not always complete in all cases, the advantages of prenatal treatment are prevailing over the complications observed in a few mothers. PMID:8481354

  19. 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

  20. Fabry Disease in Genetic Counseling Practice: Recommendations of the National Society of Genetic Counselors

    Microsoft Academic Search

    Robin L. Bennett; Kimberly A. Hart; Erin O'Rourke; John A. Barranger; Jack Johnson; Kay D. MacDermot; Gregory M. Pastores; Robert D. Steiner; Ravi Thadhani

    2002-01-01

    The objective of this document is to provide health care professionals with recommendations for genetic counseling and testing of individuals with a suspected or confirmed diagnosis of Fabry disease, with a family history of Fabry disease, and those identified as female carriers of Fabry disease. These recommendations are the opinions of a multicenter working group of genetic counselors, medical geneticists,

  1. Attention-Deficit\\/Hyperactivity Disorder: Diagnosis, Lifespan, Comorbidities, and Neurobiology

    Microsoft Academic Search

    Thomas J. Spencer; Joseph Biederman; Eric Mick

    2007-01-01

    In this report, we provide an evidence-based overview of attention-deficit\\/hyperactivity disorder (ADHD), including diagnosis, prevalence, developmental expression of symptoms, persistence, the heterogeneity of functional outcome, impairment in afflicted adults, psychiatric comorbidity, pathophysiology, genetics, psychosocial and biologic risk factors, and neurobiology. Attention-deficit\\/hyperactivity disorder is an early- onset, highly prevalent neurobehavioral disorder, with genetic, environmental, and biologic etiologies, that persists into adolescence

  2. Pneumocystis Pneumonia Diagnosis and Testing

    MedlinePLUS

    ... About CDC.gov . Fungal Diseases Share Compartir Pneumocystis pneumonia Diagnosis and Testing P. jirovecii cysts in a ... Diagnosis & Testing Treatment & Outcomes Statistics Additional Information Pneumocystis pneumonia Definition Symptoms People at Risk & Prevention Sources Diagnosis & ...

  3. who . . .GENETIC ASSOCIATION OF

    E-print Network

    Kay, Mark A.

    who . . .GENETIC ASSOCIATION OF COUNSELING DIRECTORS ROGRAMP are genetic counselors ? Genetic, medical genetics, epidemiological principles, and counseling theory with their skills in genetic risk and their families for a diverse set of genetic or genomic indications. Genetic counselors help people

  4. 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 ...

  5. Dystonia: Genetics

    MedlinePLUS

    ... Differential Disorders Frequently Asked Questions Glossary Downloadable Publications Genetics Individuals with dystonia may be concerned that their ... of inheriting the disorder. Being informed about the genetics of dystonia can also be important in the ...

  6. Genetic Discrimination

    MedlinePLUS

    ... bill, ideally passed by the completion of the Human Genome Project, would allay public fears of genetic discrimination, promote public participation in medical research, and prevent genetic discrimination. The ... and Human Services; Interim Final Rules Prohibiting Discrimination Based on ...

  7. 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

  8. An Overview of Mutation Detection Methods in Genetic Disorders

    PubMed Central

    Mahdieh, Nejat; Rabbani, Bahareh

    2013-01-01

    Genetic disorders are traditionally categorized into three main groups: single-gene, chromosomal, and multifactorial disorders. Single gene or Mendelian disorders result from errors in DNA sequence of a gene and include autosomal dominant (AD), autosomal recessive (AR), X-linked recessive (XR), X-linked dominant and Y-linked (holandric) disorders. Chromosomal disorders are due to chromosomal aberrations including numerical and structural damages. Molecular and cytogenetic techniques have been applied to identify genetic mutations leading to diseases. Accurate diagnosis of diseases is essential for appropriate treatment of patients, genetic counseling and prevention strategies. Characteristic features of patterns of inheritance are briefly reviewed and a short description of chromosomal disorders is also presented. In addition, applications of cytogenetic and molecular techniques and different types of mutations are discussed for genetic diagnosis of the pediatric genetic diseases. The purpose is to make pediatricians familiar with the applications of cytogenetic and molecular techniques and tools used for genetic diagnosis. PMID:24427490

  9. Diagnosis and therapy in neuromuscular disorders: diagnosis and new treatments in mitochondrial diseases

    Microsoft Academic Search

    S Rahman; M G Hanna

    2009-01-01

    Mitochondrial disease enters the differential diagnosis of a wide range of CNS and PNS presentations. Respiratory chain ATP production is under bigenomic genetic control. Adult mitochondrial diseases are mainly caused by mutations in mitochondrial DNA (mtDNA), and nuclear gene defects usually present with more severe childhood phenotypes. Recently, mutations in certain nuclear genes—for example POLG, MFN2 and OPA1, have been

  10. The History of Community Genetics: The Contribution of the Haemoglobin Disorders

    Microsoft Academic Search

    Bernadette Modell; Anver Kuliev

    1998-01-01

    The emerging possibilities of applying new diagnostic technologies for genetic diagnosis and screening point to the need for a discipline of community genetics. Genetic population screening for haemoglobin disorders (thalassaemias and sickle cell disorders) has been practised on a large scale for over 20 years, and basic concepts and methods of community genetics have been developed within this framework, under

  11. Diagnosis of Leishmaniasis

    MedlinePLUS

    ... message, please visit this page: About CDC.gov . Parasites - Leishmaniasis Parasites Home Share Compartir Diagnosis Light-microscopic examination of ... multiple Leishmania amastigotes (the tissue stage of the parasite). Note that each amastigote has a nucleus (red ...

  12. 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)

  13. Working with Patients: Diagnosis

    MedlinePLUS

    ... Testing Information Health Care Professionals Materials Working with Patients Diagnosis Asbestos-related conditions can be difficult to ... the toxicological characteristics and health effects of asbestos. Patient Materials Living with Asbestos-Related Illness [ HTML ] Topics ...

  14. Dementia: Diagnosis and Tests

    MedlinePLUS

    ... our e-newsletter! Aging & Health A to Z Dementia Diagnosis & Tests If you or someone you care ... To determine whether an older adult might have dementia, a healthcare professional will: Ask about the person’s ...

  15. Plague Diagnosis and Treatment

    MedlinePLUS

    ... message, please visit this page: About CDC.gov . Plague Plague Ecology & Transmission Symptoms Diagnosis & Treatment Maps & Statistics Info ... Clinicians Public Health Officials Veterinarians Prevention History of Plague Resources FAQ Related Links USGS National Wildlife Health ...

  16. Genetic Screening

    NSDL National Science Digital Library

    Irwin Slesnick

    2004-01-01

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

  17. Genetic programming

    Microsoft Academic Search

    Wolfgang Banzhaf; J. R. Koza; C. Ryan; L. Spector; C. Jacob

    2000-01-01

    The paper presents essays on genetic programming which involve topics such as: the artificial evolution of computer code, human-competitive machine intelligence by means of genetic programming, GP as automatic programming, GP application, the evolution of arbitrary computational processes and the art of genetic programming

  18. 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.

  19. Diagnosis of urticaria

    PubMed Central

    Schoepke, Nicole; Doumoulakis, Georgios; Maurer, Marcus

    2013-01-01

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

  20. Diagnosis of NF2

    MedlinePLUS

    ... an informational brochure on NF2 please click here . Genetic Testing for NF2 Massachusetts General Hospital, Boston, MA DNA diagnostics lab at MGH, phone (617 726-5721) or log in to the MGH ... Genetics Reference Laboratory, Manchester, UK Dr. Andrew Wallace - phone: ...

  1. 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

  2. Perry syndrome: a disorder to consider in the differential diagnosis of Parkinsonism.

    PubMed

    Aji, B M; Medley, G; O'Driscoll, K; Larner, A J; Alusi, S H

    2013-07-15

    A patient with a mood disorder and a Parkinsonian syndrome with frontal cognitive impairment thought to resemble progressive supranuclear palsy defied precise diagnosis until the development of respiratory compromise, prompting consideration of the diagnosis of Perry syndrome. A mutation in the dynactin 1 gene confirmed the diagnosis. Few examples of this disorder, characterised by depression, Parkinsonism, and respiratory insufficiency, have been reported but it may be more commonly recognised with the availability of genetic testing. Perry syndrome needs to be considered in the differential diagnosis of Parkinsonism, particularly in autosomal dominant pedigrees. Diagnosis early in the disease course may facilitate monitoring and prompt intervention to avoid potentially fatal respiratory failure. PMID:23628468

  3. Diagnosis of muscle diseases presenting with early respiratory failure.

    PubMed

    Pfeffer, Gerald; Povitz, Marcus; Gibson, G John; Chinnery, Patrick F

    2014-11-01

    Here we describe a clinical approach and differential diagnosis for chronic muscle diseases which include early respiratory failure as a prominent feature in their presentation (i.e. respiratory failure whilst still ambulant). These patients typically present to neurology or respiratory medicine out-patient clinics and a distinct differential diagnosis of neuromuscular aetiologies should be considered. Amyotrophic lateral sclerosis and myasthenia gravis are the important non-muscle diseases to consider, but once these have been excluded there remains a challenging differential diagnosis of muscle conditions, which will be the focus of this review. The key points in the diagnosis of these disorders are being aware of relevant symptoms, which are initially caused by nocturnal hypoventilation or diaphragmatic weakness; and identifying other features which direct further investigation. Important muscle diseases to identify, because their diagnosis has disease-specific management implications, include adult-onset Pompe disease, inflammatory myopathy, and sporadic adult-onset nemaline myopathy. Cases which are due to metabolic myopathy or muscular dystrophy are important to diagnose because of their implications for genetic counselling. Myopathy from sarcoidosis and colchicine each has a single reported case with this presentation, but should be considered because they are treatable. Disorders which have recently had their genetic aetiologies identified include hereditary myopathy with early respiratory failure (due to TTN mutations), the FHL1-related syndromes, and myofibrillar myopathy due to BAG3 mutation. Recently described syndromes include oculopharyngodistal muscular dystrophy that awaits genetic characterisation. PMID:25377282

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

    E-print Network

    Harman, Neal.A.

    Medical Genetics and Genetics Is Medical Genetics or Genetics right for me? If you are interested Medical Genetics or Genetics degrees the same? The structure of your degree will depend on each university and on their website. Medical Genetics or Genetics? The difference between Medical Genetics and Genetics is mainly down

  5. Mutation analysis in the diagnosis of cystic fibrosis

    Microsoft Academic Search

    T. Deufel; H. Rabe; T. Wieser; T. Meitinger; J. Rosenecker; R. Bertele-Harms; K. Harms; H.-B. Hadorn; A. A. Roscher

    1993-01-01

    Since the characterization of the gene encoding the cystic fibrosis transmembrane conductance regulator protein and identification of its main mutation, ?F508, causing cystic fibrosis (CF), more than 150 mutations in this gene have been reported, most of them only in a few or even single CF patients. Attempts to use mutation analysis in genetic counselling or for the diagnosis of

  6. Proposed Guidelines for the Diagnosis of Canine Idiopathic Dilated Cardiomyopathy

    Microsoft Academic Search

    Joanna Dukes-McEwan; Michele Borgarelli; Anna Tidholm; Andrea C Vollmar; Jens Häggström

    2003-01-01

    Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality in various dog breeds. The diagnosis of overt DCM is not normally problematic, although the importance of active exclusion of other causes of the dilated, hypokinetic heart is emphasised. Recent interest in human familial DCM has prompted a number of researchers to investigate the genetic basis of canine DCM.

  7. Microfluidic digital PCR enables rapid prenatal diagnosis of fetal aneuploidy

    E-print Network

    Quake, Stephen R.

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

  8. Molecular markers in the epidemiology and diagnosis of coccidioidomycosis.

    PubMed

    Duarte-Escalante, Esperanza; Frías-De-León, María Guadalupe; Zúñiga, Gerardo; Martínez-Herrera, Erick; Acosta-Altamirano, Gustavo; Reyes-Montes, María Del Rocío

    2014-01-01

    The prevalence of coccidioidomycosis in endemic areas has been observed to increase daily. To understand the causes of the spread of the disease and design strategies for fungal detection in clinical and environmental samples, scientists have resorted to molecular tools that allow fungal detection in a natural environment, reliable identification in clinical cases and the study of biological characteristics, such as reproductive and genetic structure, demographic history and diversification. We conducted a review of the most important molecular markers in the epidemiology of Coccidioides spp. and the diagnosis of coccidioidomycosis. A literature search was performed for scientific publications concerning the application of molecular tools for the epidemiology and diagnosis of coccidioidomycosis. The use of molecular markers in the epidemiological study and diagnosis of coccidioidomycosis has allowed for the typing of Coccidioides spp. isolates, improved understanding of their mode of reproduction, genetic variation and speciation and resulted in the development specific, rapid and sensitive strategies for detecting the fungus in environmental and clinical samples. Molecular markers have revealed genetic variability in Coccidioides spp. This finding influences changes in the epidemiology of coccidioidomycosis, such as the emergence of more virulent or antifungal resistant genotypes. Furthermore, the molecular markers currently used to identify Coccidioides immitis and Coccidioides posadasii are specific and sensitive. However, they must be validated to determine their application in diagnosis. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). PMID:24270069

  9. An Evolutionary Artificial Neural Network Approach for Breast Cancer Diagnosis

    Microsoft Academic Search

    Lijuan Liu; Mingrong Deng

    2010-01-01

    In this study, diagnosis of breast cancer, the second type of the most widespread cancer in women, was performed with an evolutionary artificial neural network approach based on adaptive genetic algorithm with strong macro-search capability and global optimization, which was used to optimize initial weights and thresholds of the network. Experimental results had better precision and much lower computational cost

  10. Molecular Diagnosis of Putative Stargardt Disease by Capture Next Generation Sequencing

    PubMed Central

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

    2014-01-01

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

  11. 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

  12. Diagnosis and management of primary ciliary dyskinesia

    PubMed Central

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

    2014-01-01

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

  13. Psoriatic arthritis: Epidemiology, diagnosis, and treatment

    PubMed Central

    Liu, Jung-Tai; Yeh, Horng-Ming; Liu, Shyun-Yeu; Chen, Kow-Tong

    2014-01-01

    Our understanding of psoriatic arthritis has evolved as new knowledge of the disease has emerged. However, the exact prevalence of psoriatic arthritis is unknown, and its pathogenesis has not been fully elucidated. Genetic, environmental, and immunologic factors have all been implicated in disease development. Early diagnosis and treatment have become primary objectives in clinical rheumatology. Psoriatic arthritis not only causes functional impairment, but also increases mortality risk of patients. The advent of new therapeutic agents capable of arresting the progression of joint damage is expected. However, early psoriatic arthritis assessment remains limited. The objectives of this article are to outline the epidemiology, diagnosis, and treatment of psoriatic arthritis and to suggest a paradigm for identifying early psoriatic arthritis patients. PMID:25232529

  14. Psoriatic arthritis: Epidemiology, diagnosis, and treatment.

    PubMed

    Liu, Jung-Tai; Yeh, Horng-Ming; Liu, Shyun-Yeu; Chen, Kow-Tong

    2014-09-18

    Our understanding of psoriatic arthritis has evolved as new knowledge of the disease has emerged. However, the exact prevalence of psoriatic arthritis is unknown, and its pathogenesis has not been fully elucidated. Genetic, environmental, and immunologic factors have all been implicated in disease development. Early diagnosis and treatment have become primary objectives in clinical rheumatology. Psoriatic arthritis not only causes functional impairment, but also increases mortality risk of patients. The advent of new therapeutic agents capable of arresting the progression of joint damage is expected. However, early psoriatic arthritis assessment remains limited. The objectives of this article are to outline the epidemiology, diagnosis, and treatment of psoriatic arthritis and to suggest a paradigm for identifying early psoriatic arthritis patients. PMID:25232529

  15. Prenatal Diagnosis of Sex Differentiation Disorders: The Role of Fetal Ultrasound

    Microsoft Academic Search

    ORIT PINHAS-HAMIEL; YARON ZALEL; ERIC SMITH; RAM MAZKERETH; AYALA AVIRAM; SHLOMO LIPITZ; REUVEN ACHIRON

    We describe our experience with prenatal diagnosis of sex dif- ferentiation disorders, with focus on the role of ultrasound scans for coherent assessment of prenatal diagnosis. Over a 5-yr pe- riod all cases suspected of sexual ambiguity based on abnormal ultrasonographic scans (US) or US\\/genotype US discrepancy were evaluated prenatally by three modalities: 1) repeated fetal US; 2) genetic studies,

  16. Type 2N von Willebrand disease: clinical manifestations, pathophysiology, laboratory diagnosis and molecular biology

    Microsoft Academic Search

    Claudine Mazurier; Jenny Goudemand; Lysiane Hilbert; Claudine Caron; Edith Fressinaud; Dominique Meyer

    2001-01-01

    Type 2N von Willebrand disease encompasses all patients with factor VIII deficiency caused by a markedly decreased affinity of von Willebrand factor for factor VIII. It is recessively inherited and clinically similar to mild haemophilia. The differential biological diagnosis is of major importance for providing the optimal treatment and relevant genetic counselling. This accurate diagnosis is based on an evaluation

  17. Genetics Home Reference: Core binding factor acute myeloid leukemia

    MedlinePLUS

    ... disorder catalog Conditions > Core binding factor acute myeloid leukemia On this page: Description Genetic changes Inheritance Diagnosis ... 2013 What is core binding factor acute myeloid leukemia? Core binding factor acute myeloid leukemia (CBF-AML) ...

  18. Genetics Home Reference: Cytogenetically normal acute myeloid leukemia

    MedlinePLUS

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

  19. Genetics Home Reference: 46,XX testicular disorder of sex development

    MedlinePLUS

    ... catalog Conditions > 46,XX testicular disorder of sex development On this page: Description Genetic changes Inheritance Diagnosis ... What is 46,XX testicular disorder of sex development? 46,XX testicular disorder of sex development is ...

  20. Genetics Home Reference: Congenital disorder of glycosylation type Ic

    MedlinePLUS

    ... disorder catalog Conditions > Congenital disorder of glycosylation type Ic On this page: Description Genetic changes Inheritance Diagnosis ... 2014 What is congenital disorder of glycosylation type Ic? Congenital disorder of glycosylation type Ic (known as ...

  1. 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.

  2. Genetic mutations in Gorlin-Goltz syndrome

    PubMed Central

    Daneswari, Muthumula; Reddy, Mutjumula Swamy Ranga

    2013-01-01

    Gorlin-Goltz syndrome is a rare multisystemic disease inherited in a dominant autosomal at a high level of penetrance and variable expressiveness. It is mainly characterized by basal cell carcinoma, odontogenic keratocyst and skeletal anomalies. Diagnosis is based upon established major and minor clinical and radiographic criteria and gene mutation analysis. This article presents a case of Gorlin-Goltz syndrome, its genetic predisposition, diagnosis and management. PMID:24339558

  3. Genetic mutations in Gorlin-Goltz syndrome.

    PubMed

    Daneswari, Muthumula; Reddy, Mutjumula Swamy Ranga

    2013-07-01

    Gorlin-Goltz syndrome is a rare multisystemic disease inherited in a dominant autosomal at a high level of penetrance and variable expressiveness. It is mainly characterized by basal cell carcinoma, odontogenic keratocyst and skeletal anomalies. Diagnosis is based upon established major and minor clinical and radiographic criteria and gene mutation analysis. This article presents a case of Gorlin-Goltz syndrome, its genetic predisposition, diagnosis and management. PMID:24339558

  4. Idiopathic Parkinson's disease: epidemiology, diagnosis and management.

    PubMed Central

    Ben-Shlomo, Y; Sieradzan, K

    1995-01-01

    Since the introduction of levodopa therapy for idiopathic Parkinson's disease over 20 years ago, there has been an awakening of research interest in this chronic neuro-degenerative disorder. This paper describes current understanding of the role of genetic and environmental factors in the aetiology of idiopathic Parkinson's disease and problems associated with both diagnosis and management. It briefly outlines both pharmacological and non-pharmacological options for treatment. Despite an increasing armoury of available treatments, the optimum management for this condition remains controversial. PMID:7619574

  5. Monoclonal Antibodies in Diagnosis and Therapy

    NASA Astrophysics Data System (ADS)

    Waldmann, Thomas A.

    1991-06-01

    Monoclonal antibodies have been applied clinically to the diagnosis and therapy of an array of human disorders, including cancer and infectious diseases, and have been used for the modulation of immune responses. Effective therapy using unmodified monoclonal antibodies has, however, been elusive. Recently, monoclonal antibody-mediated therapy has been revolutionized by advances such as the definition of cell-surface structures on abnormal cells as targets for effective monoclonal antibody action, genetic engineering to create less immunogenic and more effective monoclonal antibodies, and the arming of such antibodies with toxins or radionuclides to enhance their effector function.

  6. 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.

  7. [Imaging diagnosis of dementia].

    PubMed

    Ishii, Kenji

    2014-04-01

    The role of neuroimaging in the diagnosis of dementia diseases is overviewed. In the clinical practice, screening imaging examinations such as X-ray CT and MRI of the brain are useful to exclude cerebrovascular disorders, brain tumors, subdural hematomas, and normal pressure hydrocephalus from neurodegenerative disorders. After differentiating those disorders, the regional distribution patterns of atrophy, neuronal injury, or functional impairment detected by morphological MRI, perfusion SPECT, or 18F-FDG PET are useful for the differential diagnosis of neurodegenerative diseases. Cardiac scintigraphy by 123I- MIBG, dopamine transporter imaging, and amyloid imaging give us pathology specific information such as cardiac autonomic dysfunction mainly by Lewy body disease, nigral degeneration with parkinson's syndrome, and amyloid deposition with Alzheimer's disease. Those structural, functional, and pathology specific neuroimaging tools can be used not only for the early diagnosis, but also for tracing disease progression in understanding the relationship between life style diseases and dementia, and developing disease modifying therapies. PMID:24796097

  8. Guidelines for diagnosis and management of Beta-thalassemia intermedia.

    PubMed

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

    2014-10-01

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

  9. 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

  10. 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

  11. Basal cell carcinoma – diagnosis

    PubMed Central

    Bowszyc-Dmochowska, Monika; Strzelecka-W?klar, Daria; Da?czak-Pazdrowska, Aleksandra; Adamski, Zygmunt

    2013-01-01

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

  12. Genetic Resources

    Microsoft Academic Search

    Beat Boller; Stephanie L. Greene

    \\u000a Plant genetic resources (PGR) for food and agriculture consist of the diversity of genetic material contained in traditional\\u000a varieties and modern cultivars grown by farmers as well as crop wild relatives and other wild plant species that can be used\\u000a for food, feed for domestic animals, fiber, clothing, shelter, wood, timber, energy, etc. (FAO 1997). Fodder crop genetic\\u000a resources broaden

  13. Scitable: Genetics

    NSDL National Science Digital Library

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

  14. 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. [Institute for Human Genetics, Erlange (Germany)] [and others

    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.

  15. Diagnosis and differential diagnosis of breast calcifications

    SciTech Connect

    Lanyi, M.

    1987-01-01

    This book is the result of more than 10 years' intensive research into the phenomena of breast calcifications. The author, himself a decisive figure in the development of mammography, demonstrates that a careful, detailed analysis of X-rays can lead to a high degree of diagnostic certainty. Indeed, Lanyi's descriptions make one ask why mammography, which originally awakened such high hopes, is given so little attention today. Contents: historical review; critical analysis of the literature; statement of problems and goals; instruments used in the evaluation of breast microcalcifications; remarks on the pathogenesis, pathophysiology, and composition of breast calcifications; calcifications within the lobular and ductal system of the breast; calcifications in intra- and pericanalicular fibroadenomas; calcifications outside the lobular and ductal systems of the breast; differential diagnosis of microcalcifications; clinically occult, mammographically suspicious microcalcification cluster: Pre-, intra-, and postoperative measures; references, and index.

  16. 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

  17. Best Pract Res Clin Gastroenterol . Author manuscript Diagnosis and management of chronic viral hepatitis: antigens, antibodies

    E-print Network

    Paris-Sud XI, Université de

    of chronic viral hepatitis: antigens, antibodies and viral genomes St phane Chevaliezé 1 2 , Jean ; Hepatitis B Antibodies ; blood ; Hepatitis B Antigens ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; diagnosis ; drug therapy ; genetics ; Hepatitis C Antibodies ; blood ; Hepatitis C

  18. 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

  19. Pulmonary Hypertension: Diagnosis and Management

    PubMed Central

    McGoon, Michael D.; Kane, Garvan C.

    2009-01-01

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

  20. New Genetic Insights into Congenital Heart Disease

    PubMed Central

    Ware, Stephanie M.; Jefferies, John Lynn

    2012-01-01

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

  1. 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…

  2. 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....

  3. 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…

  4. About Alzheimer's Disease: Diagnosis

    MedlinePLUS

    ... health issue is causing the problem. How is Alzheimer’s disease diagnosed? A definitive diagnosis of Alzheimer’s disease can ... Clinical Trials Database . What new methods for diagnosing Alzheimer’s disease are being studied? Scientists are exploring ways to ...

  5. Diagnosis of visceral leishmaniasis

    PubMed Central

    Srivastava, Pankaj; Dayama, Anand; Mehrotra, Sanjana; Sundar, Shyam

    2010-01-01

    Leishmaniasis is a vector-borne disease with up to 350 million people at risk of infection worldwide. Among its different clinical manifestations, visceral is the most severe form. Since clinical features of visceral leishmaniasis (VL) mimic several other common diseases, accurate diagnosis of VL is crucial as the treatment is associated with significant toxicity. Invasive and risky techniques involving demonstration of the parasites in stained preparations from splenic and bone marrow aspirate is still the gold standard for VL diagnosis. Serological tests using rk39 in ELISA or rapid immunochromatographic format, Direct Agglutination Test (DAT), immunoblotting have issues related to a significant proportion of asymptomatic individuals being positive with these tests and their inability to diagnose relapses as these remain positive for several months to years after cure. PCR is the most common molecular technique successfully used for diagnosis and differentiation of species. Through this review we focus extensively on the comparative utilities of the various diagnostic tools currently available for VL, describing in depth their advantages and disadvantages, addressing the recent advances attained in the field. A simple, rapid, non invasive, accurate and cost effective marker of active VL, which can be used in field conditions, is necessary to improve diagnosis of VL. PMID:21074233

  6. Cancer: Diagnosis and Tests

    MedlinePLUS

    MENU Return to Web version Cancer | Diagnosis & Tests What screening tests should women have? Increasing age is the most important risk factor for breast cancer for most women. To help find breast cancer early, your doctor may perform a clinical breast exam (where he or she checks ...

  7. Diagnosis with Behavioral Modes

    Microsoft Academic Search

    Johan De Kleer; Brian C. Williams

    1989-01-01

    Diagnostic tasks involve identifying faulty com­ ponents from observations of symptomatic device behavior. This paper presents a general diagnos­ tic theory that uses the perspective of diagnosis as identifying consistent modes of behavior, cor­ rect or faulty. Our theory draws on the intu­ itions behind recent diagnostic theories to iden­ tify faulty components without necessarily know­ ing how they fail.

  8. Diagnosis using One disease

    E-print Network

    Spang, Rainer

    Diagnosis using computers #12;One disease Three therapies #12;Clinical Studies In average 75% 55,7% Without developing any new therapies #12;A higher resolution of dividing a disease into subtypes improves addition desirable · A patients metabolism in a bird`s eye view #12;Tissue DNA Chip Expression profile #12

  9. 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.…

  10. Computer diagnosis in cardiology

    Microsoft Academic Search

    Graham Wilfred Ewing; Elena Nikolayevna Ewing

    This article reports upon the emergence of a novel cognitive, computer-based technology which may lead to significantly improved methods of cardiological diagnosis and a rapid and inexpensive method of cardiological screening. The technology 'Virtual Scanning' illustrates how, in blood, the reaction of proteins and their reactive substrates releases light; that the colour and intensity of this bioluminescence is unique to

  11. 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)

  12. Landscape Genetics

    NSDL National Science Digital Library

    Rolf Holderegger (Swiss Federal Research Institute; )

    2008-03-01

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

  13. Genetic Counseling.

    ERIC Educational Resources Information Center

    Exceptional Parent, 1987

    1987-01-01

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

  14. 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...

  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. Genetic cerebellar ataxias.

    PubMed

    Storey, Elsdon

    2014-07-01

    This review broadly covers the commoner genetic ataxias, concentrating on their clinical features. Over the last two decades there has been a potentially bewildering profusion of newly described genetic ataxias. However, at least half of dominant ataxias (SCAs) are caused by (CAG)n repeat expansions resulting in expanded polyglutamine tracts (SCAs 1, 2, 3, 6, 7, 17, and DRPLA), although of the remainder only SCAs 8, 10, 12, 14, 15/16, and 31 are frequent enough that the described phenotype is probably representative. Though the SCAs can be difficult to separate clinically, variations in prevalence in different populations, together with various clinical and radiological features, at least help to order the pretest probabilities. The X-linked disorder, fragile-X tremor ataxia syndrome occurs in fragile-X permutation carriers, and typically causes a late-onset ataxia-plus syndrome. The recessive ataxias are not named systematically: The most frequent are Friedreich, ataxia telangiectasia, ARSACS, AOA1 and 2, and the various POLG syndromes. Although rare, several other recessive disorders such as AVED are potentially treatable and should not be missed. Another group of genetic ataxias are the dominant episodic ataxias, of which EA1 and EA2 are the most important. Lastly, the neurologist's role in ongoing management, rather than just diagnosis, is addressed. PMID:25192506

  17. Genetics of hepatobiliary diseases.

    PubMed

    Juran, Brian D; Lazaridis, Konstantinos N

    2006-05-01

    With the recent publication of the first human map of genetic variation (ie, Human Haplotype Map), genomic-based discoveries will likely affect not only the research bench but also the bedside. These advances will improve the understanding of the genetics of hepatobiliary diseases, resulting in better prevention measures and diagnosis as well as more effective therapies. Currently, alcoholic liver disease, nonalcoholic fatty liver disease, and symptomatic gallbladder stones affect a sizable portion of the population. On the other hand, chronic cholestatic liver diseases, hepatocellular carcinoma, and polycystic liver disease, although rare, shorten life expectancy and diminish the quality of life of patients. In the genomic era, we have the opportunity to start dissecting the susceptibility genetic variants of liver diseases. We are now in a position to begin elucidating the complex genotype/phenotype relationships of liver diseases with the anticipation to understand disease pathogenesis better. These efforts will require the application of genomic-based approaches in large well-organized translational studies in the diseases of interest. PMID:16678073

  18. Melasma: Diagnosis, Treatment, and Outcome

    MedlinePLUS

    ... Signs, symptoms Who gets, causes Diagnosis, treatment Tips Bedbugs Signs, symptoms Who gets, causes Diagnosis, treatment Tips ... 2015 American Academy of Dermatology. All rights reserved. Reproduction or republication strictly prohibited without prior written permission.

  19. Hives: Diagnosis, Treatment, and Outcome

    MedlinePLUS

    ... H Hives Diagnosis, treatment Hives: Diagnosis, treatment, and outcome How do dermatologists diagnose hives? When a patient ... hours or less, but bouts can last longer. Outcome A few people have chronic hives (lasting more ...

  20. When to offer genetic testing for pulmonary arterial hypertension.

    PubMed

    Chung, Wendy K; Austin, Eric D; Best, D Hunter; Brown, Lynette M; Elliott, C Gregory

    2015-04-01

    Genetic testing is poised to play a greater role in the diagnosis and management of pulmonary arterial hypertension (PAH). Physicians who manage PAH should know the heritable PAH phenotypes, inheritance patterns, and responsible genes. They also should know indications, potential risks and benefits, and the issues surrounding genetic counselling and testing for patients with PAH. PMID:25840103

  1. The impact of the Human Genome Project on medical genetics

    Microsoft Academic Search

    Stephanie J Williams; Nicholas K Hayward

    2001-01-01

    The near completion of the Human Genome Project stands as a remarkable achievement, with enormous implications for both science and society. For scientists, it is the first step in a complex process that will lead to important advances in the diagnosis and treatment of many diseases. Society, meanwhile, must prevent genetic discrimination, and protect genetic privacy through appropriate legislation.

  2. Accuracy of the clinical diagnosis of Down Syndrome

    E-print Network

    2004-01-01

    Objectives- to determine the accuracy of clinical diagnosis of Down syndrome, identify problems in reaching a diagnosis, to provide recommendations for improvement and estimate a minimum prevalence for all types of Down syndrome. Design- A retrospective observational study was carried out over a five-year period. Genesis, a database located in the Department of Medical genetics, was used to identify the number of Down syndrome karyotypes including trisomy, translocation, and mosaic sample variants. Age of diagnosis was determined using date of receipt. Karyotyping requests for a clinical diagnosis of Down syndrome were also identified. Patient notes and cytogenetic laboratory reports were used to identify clinical indication for karyotyping. Setting- Regional Genetics Centre, covering all cytogenetic analyses for referrals within the entire Northern Ireland population. Results- 208 postnatal cases of Down syndrome were identified, 197 (94.7 %) trisomy, 3 (1.45 %) translocation, and 8 (3.85%) mosaic variants. 112 (54.8%) were male and 96 (46.2%) female. 268 samples were taken to confirm or exclude a clinical diagnosis of Down syndrome. 185 of these had Down syndrome, 77 were normal, and 6 had another abnormality. 90 % and 100 % of trisomy and

  3. Diagnosis, admission, discharge.

    PubMed

    Everard, Mark

    2009-06-01

    The respiratory syncytial virus should be considered as the most likely pathogen in an infant or young child with a significant acute lower respiratory tract infection during the characteristic epidemic season. While the diagnosis of an RSV infection is relatively straight forward, the clinical diagnosis applied to the associate illness is far less clear cut. Criteria for assessment is based on clinical assessment of severity at examination and associated risk factors. Social factors may further influence the likelihood of admission. Guidelines are consistent in noting that there are no scoring systems or other tests that can reliably predict the need for supportive care or HDU admission. Criteria for the administration of oxygen vary. There are marked differences in the duration of hospitalisation for RSV admission between the USA, UK and Scandinavia. Longer length of admission is associated with significantly higher rates of nosicomial infection. PMID:19651395

  4. 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

  5. [Diagnosis of retrocecal appendicitis].

    PubMed

    Guzeev, A I

    1975-04-01

    Based on the analysis of case reports of 223 patients, operated upon for acute retrocecal appendicitis, there was found a definite dependence between the clinical course and anatomical features of the appendix position. Intramural, intraparietal and retroperitoneal forms of the appendix localization present the extreme dificulty for diagnosis. In free localization of the appendicular process retrocecally a typical clinical picture of the disease is observed. PMID:1224517

  6. Differential Diagnosis of Insomnia

    Microsoft Academic Search

    Michael Saletu; Bernd Saletu

    \\u000a Insomnia is both a symptom and a clinical entity in itself. There are three well-defined insomnia conditions that are often\\u000a referred to as primary insomnias. In addition, there are a number of medical, psychiatric, and social factors that can lead\\u000a to comorbid insomnia. While formulating a differential diagnosis one must think of the mental and medical conditions the person\\u000a with

  7. Diagnosis and Classification

    Microsoft Academic Search

    Gilles Grateau; Katia Stankovic

    \\u000a A high degree of clinical suspicion in the context of a great diversity of clinical symptoms remains essential to make the\\u000a diagnosis of amyloidosis that still relies on tissue biopsy. Standard tissue staining should be completed with Congo red as\\u000a this stain gives a specific “apple-green birefringence” for amyloid under polarization. Identifying the type of amyloidosis\\u000a is crucial to determine

  8. Prevention, Diagnosis and Services

    Microsoft Academic Search

    Eva Bermejo; María Luisa Martínez-Frías

    \\u000a This chapter summarizes how prevention, diagnosis and services can result from the activities of a research programme on the group of rare diseases constituted by congenital anomalies.\\u000a The Spanish Collaborative Study of Congenital Malformations (ECEMC) is a research programme based on a case-control registry\\u000a of consecutive newborn infants with congenital anomalies. Its aim is the prevention of this group of

  9. Deformation Zone Diagnosis

    NSDL National Science Digital Library

    2014-09-14

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

  10. Case for diagnosis.

    PubMed

    Mesquita, Ludmila de Sousa Ursino; Sherlock, Jonnia; Portugal, Fedro Menezes; Mota, Lívia de Souza; Fakhouri, Ricardo; da Silva, Samuel Freire

    2014-01-01

    Ostraceous psoriasis is a rare form of psoriasis, characterized by lesions with firmly adhered thick scales, in various colors, with surfaces resembling oysters shells. The protracted course of clinical presentation allied with peculiar lesions and histopathological examination permit the diagnosis. Lesions are usually resistant to topical medications, requiring systemic treatment. It is important that dermatologists are able to diagnose the unusual forms of psoriasis to avoid iatrogeny. We report the case of a patient with ostraceous psoriasis treated with methotrexate. PMID:25184935

  11. Ultrasound Diagnosis of Penile Fracture

    Microsoft Academic Search

    Jason T. Nomura; Paul R. Sierzenski

    2010-01-01

    Background: Rupture of the corpus cavernosum, penile fracture, is an uncommon occurrence. Diagnosis is straightforward when classical historical and physical examination findings are present. However, atypical presentations can make the diagnosis difficult. Objectives: Review the literature supporting use of ultrasound for the diagnosis of penile fracture. Review of the ultrasonographic findings in patients with penile fracture. Case Report: A 32-year-old

  12. Coping with a Cancer Diagnosis

    MedlinePLUS

    ... FACTS FOR LIFE Coping With a Breast Cancer Diagnosis Coping with breast cancer A breast cancer diagnosis can cause a wide range of feelings. Denial, ... They are there to help: • Lend support from diagnosis through treatment and ... • Gather information about breast cancer. A social worker or counselor can also help ...

  13. Diagnosis of cholangiocarcinoma

    PubMed Central

    2008-01-01

    Cholangiocarcinoma is suspected based on signs of biliary obstruction, abnormal liver function tests, elevated tumor markers (carbohydrate antigen 19-9 and carcinoembryonic antigen), and ultrasonography showing a bile stricture or a mass, especially in intrahepatic cholangiocarcinoma. Magnetic resonance imaging (MRI) or computed tomography (CT) is performed for the diagnosis and staging of cholangiocarcinomas. However, differentiation of an intraductal cholangiocarcinoma from a hypovascular metastasis is limited at imaging. Therefore, reasonable exclusion of an extrahepatic primary tumor should be performed. Differentiating between benign and malignant bile duct stricture is also difficult, except when metastases are observed. The sensitivity of fluorodeoxyglucose positron emission tomography is limited in small, infiltrative, and mucinous cholangiocarcinomas. When the diagnosis of a biliary stenosis remains indeterminate at MRI or CT, endoscopic imaging (endoscopic or intraductal ultrasound, cholangioscopy, or optical coherence tomography) and tissue sampling should be carried out. Tissue sampling has a high specificity for diagnosing malignant biliary strictures, but sensitivity is low. The diagnosis of cholangiocarcinoma is particularly challenging in patients with primary sclerosing cholangitis. These patients should be followed with yearly tumor markers, CT, or MRI. In the case of dominant stricture, histological or cytological confirmation of cholangiocarcinoma should be obtained. More studies are needed to compare the accuracy of the various imaging methods, especially the new intraductal methods, and the imaging features of malignancy should be standardized. PMID:18773062

  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. The genetic landscape of autism spectrum disorders.

    PubMed

    Rosti, Rasim O; Sadek, Abdelrahim A; Vaux, Keith K; Gleeson, Joseph G

    2014-01-01

    Autism spectrum disorders (ASDs) are a group of heterogeneous neurodevelopmental disorders that show impaired communication and socialization, restricted interests, and stereotypical behavioral patterns. Recent advances in molecular medicine and high throughput screenings, such as array comparative genomic hybridization (CGH) and exome and whole genome sequencing, have revealed both novel insights and new questions about the nature of this spectrum of disorders. What has emerged is a better understanding about the genetic architecture of various genetic subtypes of ASD and correlations of genetic mutations with specific autism subtypes. Based on this new information, we outline a strategy for advancing diagnosis, prognosis, and counseling for patients and families. PMID:24116704

  16. Genetics of childhood-onset schizophrenia.

    PubMed

    Asarnow, Robert F; Forsyth, Jennifer K

    2013-10-01

    Schizophrenia is a heritable disorder. The genetic architecture of schizophrenia is complex and heterogeneous. This article discusses genetic studies of childhood-onset schizophrenia (COS) and compares findings in familial aggregation, common allele, and rare allele studies of COS with those for adult-onset schizophrenia (AOS). COS seems to be a rare variant of AOS with greater familial aggregation of schizophrenia spectrum disorders and higher occurrence of rare allelic variants. The usefulness of genetic screening for diagnosis and individualized treatment is limited; however, identifying common pathways through which multiple genes adversely affect neural systems offers great promise toward developing novel pharmacologic interventions. PMID:24012080

  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. [Delayed diagnosis of juvenile Huntington's diseases: case report].

    PubMed

    Meza Escobar, Luis Enrique; Orozco, Jorge Luis; Takeuchi, Yuri; Ariza, Yoseth; Pachajoa, Harry

    2014-02-01

    Huntington's disease is a neurodegenerative disease that is clinically manifested as mood and personality changes, loss of cognitive functions and choreiform movements. The pattern of inheritance is autosomic dominant. It is due to the gradual expansion of a cytosine, adenine, guanine trinucleotide in a gene that codifies the protein Huntington. The molecular diagnosis must be performed to confirm the diagnosis. Genetic counseling must be carefully done due to the high suicide risk among these patients. We present the case of a fourteen-year-old male with a severe disease, poor social support and an unclear pattern of inheritance. PMID:24566795

  19. Wilson's disease: acute and presymptomatic laboratory diagnosis and monitoring

    PubMed Central

    Gaffney, D; Fell, G; O'Reilly, D

    2000-01-01

    Wilson's disease, the most common inherited disorder of copper metabolism, is a recessive genetic condition. The clinical presentation of Wilson's disease is very variable. It is characterised by low serum copper and caeruloplasmin concentrations coupled with the pathological accumulation of copper in the tissues. However, there are diagnostic difficulties and these are discussed. The current value of DNA diagnosis, both in gene tracking in families or as applied to de novo cases, is examined. Wilson's disease can be treated successfully but treatment must be life long. Patients are best treated by specialist centres with experience and expertise in the condition. Key Words: Wilson's disease • copper • diagnosis PMID:11127261

  20. [Sequencing technology in gene diagnosis and its application].

    PubMed

    Yibin, Guo

    2014-11-01

    The study of gene mutation is one of the hot topics in the field of life science nowadays, and the related detection methods and diagnostic technology have been developed rapidly. Sequencing technology plays an indispensable role in the definite diagnosis and classification of genetic diseases. In this review, we summarize the research progress in sequencing technology, evaluate the advantages and disadvantages of 1(st) ~3(rd) generation of sequencing technology, and describe its application in gene diagnosis. Also we made forecasts and prospects on its development trend. PMID:25567870

  1. Cancer Genetics Professionals

    Cancer.gov

    $data$data Cancer Genetics Professionals 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

  2. Genetic Counseling (For Parents)

    MedlinePLUS

    ... how can they help your family? What Is Genetic Counseling? Genetic counseling is the process of: evaluating ... where a genetic counselor comes in. Continue About Genetic Counselors Genetic counselors are professionals who have completed ...

  3. Reimbursement for Genetic Testing

    MedlinePLUS

    Reimbursement for Genetic Testing You are here Home Testing & Services Testing for genetic conditions Reimbursement for Genetic Testing Testing for genetic ... insurance coverage and reimbursement process. Twitter YouTube RSS Genetics and Health How Genes Work Genes, Lifestyle, & Environment ...

  4. [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

  5. RNA genetics

    SciTech Connect

    Domingo, E. (Instituto de Biologia Molecular, Facultad de Ciencias, Universidad Autonoma de Madrid, Canto Blanco, Madrid (ES)); Holland, J.J. (California Univ., San Diego, La Jolla, CA (USA). Dept. of Biology); Ahlquist, P. (Wisconsin Univ., Madison, WI (USA). 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 Disorders

    MedlinePLUS

    ... is a small piece of hereditary material called DNA that controls some aspect of a person’s physical ... who have an increased risk of a disease. DNA: The genetic material that is passed down from ...

  7. Genetic Mapping

    MedlinePLUS

    ... any scientist was a primary goal of the Human Genome Project (HGP). One of these tools is genetic mapping, ... successful sequencing and physical mapping of the entire human genome, has revolutionized ... of page Last Reviewed: February 27, 2012

  8. Genetic Alliance

    MedlinePLUS

    Search form 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 ...

  9. 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

  10. Principles of genetics and their clinical application in the neonatal intensive care unit.

    PubMed

    Schiefelbein, Julieanne H; Cheeseman, Susan E

    2009-03-01

    The neonate born with a genetic defect or fetal anomaly presents a challenge to the neonatal intensive care unit team. Typically genetic disorders are thought of as being rare; however, this is not true, and it is becoming increasingly evident as knowledge and technology progress. A definitive diagnosis is essential for management and care of the neonate and the neonate's family. An evidence-based approach to the neonate who has a suspected genetic anomaly is essential to provide accurate diagnosis and to guide ongoing care. This article gives an overview of basic genetics and genetic counseling, and applies the principles to two case studies. PMID:19237045

  11. Recently Available Techniques Applicable to Genetic Problems in the Middle East

    Microsoft Academic Search

    Pinar T. Ozand; Ali Al Odaib; Nadia Sakati; Ali M. Al-Hellani

    2005-01-01

    In this paper, we address the preventive health aspects of genetic problems in the Middle East and provide guidelines to prioritize preventive strategies. Applications of various novel genetic techniques such as comprehensive neonatal screening, high throughput heterozygote detection, preimplantation genetic diagnosis, Affymetrix systems, the NanoChip system and a new way of sensitive karyotyping for single-cell chromosome abnormalities are discussed. In

  12. 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…

  13. Genetic sequence analysis of inherited bleeding diseases

    PubMed Central

    Peyvandi, Flora; Kunicki, Tom

    2013-01-01

    The genes encoding the coagulation factor proteins were among the first human genes to be characterized over 25 years ago. Since then, significant progress has been made in the translational application of this information for the 2 commonest severe inherited bleeding disorders, hemophilia A and B. For these X-linked disorders, genetic characterization of the disease-causing mutations is now incorporated into the standard of care and genetic information is used for risk stratification of treatment complications. With electronic databases detailing >2100 unique mutations for hemophilia A and >1100 mutations for hemophilia B, these diseases are among the most extensively characterized inherited diseases in humans. Experience with the genetics of the rare bleeding disorders is, as expected, less well advanced. However, here again, electronic mutation databases have been developed and provide excellent guidance for the application of genetic analysis as a confirmatory approach to diagnosis. Most recently, progress has also been made in identifying the mutant loci in a variety of inherited platelet disorders, and these findings are beginning to be applied to the genetic diagnosis of these conditions. Investigation of patients with bleeding phenotypes without a diagnosis, using genome-wide strategies, may identify novel genes not previously recognized as playing a role in hemostasis. PMID:24124085

  14. Genetic sequence analysis of inherited bleeding diseases.

    PubMed

    Peyvandi, Flora; Kunicki, Tom; Lillicrap, David

    2013-11-14

    The genes encoding the coagulation factor proteins were among the first human genes to be characterized over 25 years ago. Since then, significant progress has been made in the translational application of this information for the 2 commonest severe inherited bleeding disorders, hemophilia A and B. For these X-linked disorders, genetic characterization of the disease-causing mutations is now incorporated into the standard of care and genetic information is used for risk stratification of treatment complications. With electronic databases detailing >2100 unique mutations for hemophilia A and >1100 mutations for hemophilia B, these diseases are among the most extensively characterized inherited diseases in humans. Experience with the genetics of the rare bleeding disorders is, as expected, less well advanced. However, here again, electronic mutation databases have been developed and provide excellent guidance for the application of genetic analysis as a confirmatory approach to diagnosis. Most recently, progress has also been made in identifying the mutant loci in a variety of inherited platelet disorders, and these findings are beginning to be applied to the genetic diagnosis of these conditions. Investigation of patients with bleeding phenotypes without a diagnosis, using genome-wide strategies, may identify novel genes not previously recognized as playing a role in hemostasis. PMID:24124085

  15. [Genetic diagnostic testing in inherited retinal dystrophies].

    PubMed

    Kohl, S; Biskup, S

    2013-03-01

    Inherited retinal dystrophies are clinically and genetically highly heterogeneous. They can be divided according to the clinical phenotype and course of the disease, as well as the underlying mode of inheritance. Isolated retinal dystrophies (i.e., retinitis pigmentosa, Leber's congenital amaurosis, cone and cone-rod dystrophy, macular dystrophy, achromatopsia, congenital stationary nightblindness) and syndromal forms (i.e., Usher syndrome, Bardet-Biedl syndrome) can be differentiated. To date almost 180 genes and thousands of distinct mutations have been identified that are responsible for the different forms of these blinding illnesses. Until recently, there was no adequate diagnostic genetic testing available. With the development of the next generation sequencing technologies, a comprehensive genetic screening analysis for all known genes for inherited retinal dystrophies has been established at reasonable costs and in appropriate turn-around times. Depending on the primary clinical diagnosis and the presumed mode of inheritance, different diagnostic panels can be chosen for genetic testing. Statistics show that in 55-80 % of the cases the genetic defect of the inherited retinal dystrophy can be identified with this approach, depending on the initial clinical diagnosis. The aim of any genetic diagnostics is to define the genetic cause of a given illness within the affected patient and family and thereby i) confirm the clinical diagnosis, ii) provide targeted genetic testing in family members, iii) enable therapeutic intervention, iv) give a prognosis on disease course and progression and v) in the long run provide the basis for novel therapeutic approaches and personalised medicine. PMID:23208805

  16. Diagnosis of DVT

    PubMed Central

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

    2012-01-01

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

  17. Biomarkers, genetics and cancer

    SciTech Connect

    Anton-Guirgis, H.; Lynch, H.T.

    1985-01-01

    Biological markers can greatly facilitate identification of individuals at high cancer risk. This volume surveys the entire field of biological markers and how they promote early diagnosis of various hereditary cancer forms. Chapters written in down-to-earth style make the data relevant to practicing clinicians as well as research scientists. Markers for site-specific tumors are investigated from the standpoints of etiology and carcinogenesis. Particular attention is given to cancer genetic settings that could serve as models for further research. Methods of identifying both those at high cancer risk and those in a pre-cancerous state are clearly explained. Specific areas covered include polymorphic markers, multiple biological markers, hereditary adenomatosis, and carcino-embryonic antigens. Research findings from studies of twins, families, and first degree relatives offer valuable insights into heritable cancer syndromes.

  18. [Diagnosis of hereditary angioedema].

    PubMed

    Bouillet, Laurence

    2015-01-01

    Hereditary angioedema is a rare disease, potentially life-threatening. It requires a specific treatment. Angioedema without wheals associated with abdominal attacks are very specific of this disease. Antigenemy and functional C1Inhibitor assays are necessary for the diagnosis. The hereditary angioedema with normal C1Inh (type III) is a diagnostic challenge. Bradykinin, secondary to kallikrein-kinin system activation is the key mediator of hereditary angioedema. Female are more symptomatic. Attacks can be induced by menstruations, pregnancies or contraceptive pills. PMID:25511656

  19. [Diagnosis of male infertility].

    PubMed

    Matsumoto, O; Imanishi, O; Okuda, Y; Shinozaki, M; Kamidono, S

    1991-11-01

    The diagnostic methods for male infertility in our clinic are reviewed, and the following are emphasized. In azoospermia, examinations for obstructive azoospermia such as testicular biopsy should be made focussing on patients with 10 ml or higher testicular volume and with 20 mIU/ml or lower serum FSH level. In hypospermic patients, examination of post-ejaculated urine and ultrasonotomography examination of prostate are necessary for the diagnosis of incomplete retrograde ejaculation and obstruction or stenosis of the ejaculatory ducts. PMID:1767758

  20. Case for diagnosis*

    PubMed Central

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

    2014-01-01

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

  1. Genetic screening

    PubMed Central

    Andermann, Anne; Blancquaert, Ingeborg

    2010-01-01

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

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

    PubMed

    Blau, Nenad; Shen, Nan; Carducci, Carla

    2014-07-01

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

  3. Genetic diagnosis of lymph-node metastasis in colorectal cancer

    Microsoft Academic Search

    N. Hayashi; I. Ito; Y. Nakamura; A. Yanagisawa; Y. Kato; S. Nakamori; S. Imaoka; H. Watanabe; M. Ogawa

    1995-01-01

    If a regional lymph node taken during surgery for colorectal cancer is found to be free of tumour on histological examination this is taken to be a good sign. However, conventional staining may not be sensitive enough. Mutant-allele-specific amplification (MASA) is a technique that can detect, at the level of an individual cell, micrometastases to lymph nodes that are histologically

  4. [Genetic diagnosis on hypertriglyceridemia-analysis for LPL gene mutations].

    PubMed

    Takagi, Atsuko; Ikeda, Yasuyuki

    2013-09-01

    Human LPL is a glycoprotein enzyme with a molecular mass of 61 kDa, and it plays a key role in regulating the triglyceride (TG) levels in circulation by hydrolyzing TGs in TG-rich lipoproteins at the first step in their metabolism. Homozygous or compound heterozygous LPL deficiency causes severe fasting hypertriglyceridemia. Heterozygous LPL deficiency usually results in a normolipidemic state, but this may cause mild hypertriglyceridemia if heterozygotes are exposed to factors, such as high alcohol intake and/or a hyperinsulinemic state. Severe fasting hypertriglyceridemia is mainly caused by abnormalities of the LPL gene, whereas there are some cases caused by gene defects relating to synthesis and transport of LPL such as LMF and GPIHBP1, and by an autoantibody to LPL acting as inhibitor of LPL. PMID:24205716

  5. Five cases of paroxysmal kinesigenic dyskinesia by genetic diagnosis

    PubMed Central

    CHEN, GUO-HONG

    2015-01-01

    Paroxysmal kinesigenic dyskinesia (PKD) is an autosomal dominant disorder and PRRT2 is the causative gene of PKD. The aim of this study was to investigate PRRT2 mutations in patients who were clinically diagnosed with PKD. Nine PKD cases, including four familial cases and five sporadic cases, were selected. Peripheral blood was drawn after obtaining informed consent, and genomic DNA was extracted by a standard protocol. Sanger sequencing was performed for the screening of PRRT2 mutations. A total of five cases were detected to harbor PRRT2 mutations. Four familial cases carried a c.649dupC (p.Arg217Profs*8) mutation, while one sporadic case and his asymptomatic father carried a c.133-136delCCAG (p.Pro45Argfs*44) mutation. PRRT2 mutations were not identified in the remaining cases. The study further confirmed that PRRT2 was a causative gene of PKD and implied that PRRT2 mutation has incomplete penetrance. PMID:25667652

  6. Diagnosis of syphilis.

    PubMed

    Luger, A

    1981-01-01

    The demonstration of Treponema pallidum in early specimens is still the most important procedure for definite diagnosis of the disease. Nonspecific lipoidal antigen tests, as well as assays using T. pallidum antigen, are used for the detection of antibodies in sera. The techniques, the interpretation of the results, the onset and limits of reactivity, as well as the sources of error of the VDRL (RPR), FTA-ABS, TPHA (MHA-TP, AMHA-TP), IgM FTA-ABS, I9S IgM-FTA-ABS, and IgM-SPHA tests are described. The presence of 19S IgM antibodies against T. pallidum indicates activity of the disease and their disappearance is evidence of cure. Positive results in the VDRL test are also strongly suggestive of active disease but are less precise. A TPHA index for CSF of more than 100 and a positive result in the IgM-SPHA test on CSF are indicative for neurosyphilis.A haemagglutination assay is suggested for screening, if possible combined with the VDRL test. The FTA-ABS test is recommended for confirmation of the diagnosis and the response to treatment can be assessed by the IgM-SPHA test or by changes in the VDRL titre. PMID:7032735

  7. 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

  8. Orally Based Diagnosis of Celiac Disease: Current Perspectives

    Microsoft Academic Search

    L. Pastore; G. Campisi; D. Compilato; L. Lo Muzio

    2008-01-01

    Celiac disease (CD) is a lifelong immune-mediated disorder caused by the ingestion of wheat gluten in genetically susceptible persons. Most cases of CD are atypical and remain undiagnosed, which exposes the individuals to the risk of life-threatening complications. Serologic endomysial and tissue transglutaminase antibody tests are used to screen at-risk individuals, although a firm diagnosis requires demonstration of characteristic histopathologic

  9. 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

  10. Genetic Engineering

    NSDL National Science Digital Library

    Morrissette-Johnson, Winona

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

  11. Diagnosis of Lyme Borreliosis

    PubMed Central

    Aguero-Rosenfeld, Maria E.; Wang, Guiqing; Schwartz, Ira; Wormser, Gary P.

    2005-01-01

    A large amount of knowledge has been acquired since the original descriptions of Lyme borreliosis (LB) and of its causative agent, Borrelia burgdorferi sensu stricto. The complexity of the organism and the variations in the clinical manifestations of LB caused by the different B. burgdorferi sensu lato species were not then anticipated. Considerable improvement has been achieved in detection of B. burgdorferi sensu lato by culture, particularly of blood specimens during early stages of disease. Culturing plasma and increasing the volume of material cultured have accomplished this. Further improvements might be obtained if molecular methods are used for detection of growth in culture and if culture methods are automated. Unfortunately, culture is insensitive in extracutaneous manifestations of LB. PCR and culture have high sensitivity on skin samples of patients with EM whose diagnosis is based mostly on clinical recognition of the lesion. PCR on material obtained from extracutaneous sites is in general of low sensitivity, with the exception of synovial fluid. PCR on synovial fluid has shown a sensitivity of up to >90% (when using four different primer sets) in patients with untreated or partially treated Lyme arthritis, making it a helpful confirmatory test in these patients. Currently, the best use of PCR is for confirmation of the clinical diagnosis of suspected Lyme arthritis in patients who are IgG immunoblot positive. PCR should not be used as the sole laboratory modality to support a clinical diagnosis of extracutaneous LB. PCR positivity in seronegative patients suspected of having late manifestations of LB most likely represents a false-positive result. Because of difficulties in direct methods of detection, laboratory tests currently in use are mainly those detecting antibodies to B. burgdorferi sensu lato. Tests used to detect antibodies to B. burgdorferi sensu lato have evolved from the initial formats as more knowledge on the immunodominant antigens has been collected. The recommendation for two-tier testing was an attempt to standardize testing and improve specificity in the United States. First-tier assays using whole-cell sonicates of B. burgdorferi sensu lato need to be standardized in terms of antigen composition and detection threshold of specific immunoglobulin classes. The search for improved serologic tests has stimulated the development of recombinant protein antigens and the synthesis of specific peptides from immunodominant antigens. The use of these materials alone or in combination as the source of antigen in a single-tier immunoassay may someday replace the currently recommended two-tier testing strategy. Evaluation of these assays is currently being done, and there is evidence that certain of these antigens may be broadly cross-reactive with the B. burgdorferi sensu lato species causing LB in Europe. PMID:16020686

  12. [Genetics of oculocutaneous albinism].

    PubMed

    Zühlke, C; Stell, A; Käsmann-Kellner, B

    2007-08-01

    Albinism comprises a heterogeneous group of nonprogressive genetic disorders characterized by the absence of pigmentation in the skin, hair, and/or eyes. Hypopigmentation or complete lack of pigmentation is caused by an enzyme deficiency involving the production, metabolism, or distribution of melanin. Clinically, oculocutaneous and ocular types, as well as syndromes associated with albinism resulting from mutations in at least 14 genes, are distinguishable. Most frequent is oculocutaneous albinism (OCA), which is subdivided nowadays into four forms, OCA 1-OCA 4. OCA is inherited as an autosomal recessive trait. Clinical differentiation of OCA types is difficult due to the observed range of phenotypic variation. Thus, genetic analysis may be helpful with respect to a precise diagnosis. Sequencing of the four genes associated with OCA detects variations in approximately 60-70% of German patients with albinism. The majority of German patients are affected by OCA 1 resulting from mutations in the gene for tyrosinase, the key enzyme in the synthesis of melanin pigment. Worldwide, OCA2 is the most frequent form of albinism. PMID:17646993

  13. Genetic Determinants of Urolithiasis

    PubMed Central

    Monico, Carla G.; Milliner, Dawn S.

    2012-01-01

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

  14. DIAGNOSIS NUMBER OF CASES CARDIOVASCULAR

    E-print Network

    Schladow, S. Geoffrey

    DIAGNOSIS NUMBER OF CASES CARDIOVASCULAR Cardiovascular disease .........................................................36 Crop Disorder.....................................................12 Digestive Disease/Plant/worms...........................14 Liver disease ......................................................14 Liver tumor

  15. Recent advances in primary ciliary dyskinesia genetics.

    PubMed

    Kurkowiak, Ma?gorzata; Zi?tkiewicz, Ewa; Witt, Micha?

    2015-01-01

    Primary ciliary dyskinesia (PCD) is a rare genetically heterogeneous disorder caused by the abnormal structure and/or function of motile cilia. The PCD diagnosis is challenging and requires a well-described clinical phenotype combined with the identification of abnormalities in ciliary ultrastructure and/or beating pattern as well as the recognition of genetic cause of the disease. Regarding the pace of identification of PCD-related genes, a rapid acceleration during the last 2-3?years is notable. This is the result of new technologies, such as whole-exome sequencing, that have been recently applied in genetic research. To date, PCD-causative mutations in 29 genes are known and the number of causative genes is bound to rise. Even though the genetic causes of approximately one-third of PCD cases still remain to be found, the current knowledge can already be used to create new, accurate genetic tests for PCD that can accelerate the correct diagnosis and reduce the proportion of unexplained cases. This review aims to present the latest data on the relations between ciliary structure aberrations and their genetic basis. PMID:25351953

  16. Recent advances in primary ciliary dyskinesia genetics

    PubMed Central

    Kurkowiak, Ma?gorzata; Zi?tkiewicz, Ewa; Witt, Micha?

    2015-01-01

    Primary ciliary dyskinesia (PCD) is a rare genetically heterogeneous disorder caused by the abnormal structure and/or function of motile cilia. The PCD diagnosis is challenging and requires a well-described clinical phenotype combined with the identification of abnormalities in ciliary ultrastructure and/or beating pattern as well as the recognition of genetic cause of the disease. Regarding the pace of identification of PCD-related genes, a rapid acceleration during the last 2–3?years is notable. This is the result of new technologies, such as whole-exome sequencing, that have been recently applied in genetic research. To date, PCD-causative mutations in 29 genes are known and the number of causative genes is bound to rise. Even though the genetic causes of approximately one-third of PCD cases still remain to be found, the current knowledge can already be used to create new, accurate genetic tests for PCD that can accelerate the correct diagnosis and reduce the proportion of unexplained cases. This review aims to present the latest data on the relations between ciliary structure aberrations and their genetic basis. PMID:25351953

  17. Genetic Profiling for Risk Reduction in Human Cardiovascular Disease

    PubMed Central

    Puckelwartz, Megan J.; McNally, Elizabeth M.

    2014-01-01

    Cardiovascular disease is a major health concern affecting over 80,000,000 people in the U.S. alone. Heart failure, cardiomyopathy, heart rhythm disorders, atherosclerosis and aneurysm formation have significant heritable contribution. Supported by familial aggregation and twin studies, these cardiovascular diseases are influenced by genetic variation. Family-based linkage studies and population-based genome-wide association studies (GWAS) have each identified genes and variants important for the pathogenesis of cardiovascular disease. The advent of next generation sequencing has ushered in a new era in the genetic diagnosis of cardiovascular disease, and this is especially evident when considering cardiomyopathy, a leading cause of heart failure. Cardiomyopathy is a genetically heterogeneous disorder characterized by morphologically abnormal heart with abnormal function. Genetic testing for cardiomyopathy employs gene panels, and these panels assess more than 50 genes simultaneously. Despite the large size of these panels, the sensitivity for detecting the primary genetic defect is still only approximately 50%. Recently, there has been a shift towards applying broader exome and/or genome sequencing to interrogate more of the genome to provide a genetic diagnosis for cardiomyopathy. Genetic mutations in cardiomyopathy offer the capacity to predict clinical outcome, including arrhythmia risk, and genetic diagnosis often provides an early window in which to institute therapy. This discussion is an overview as to how genomic data is shaping the current understanding and treatment of cardiovascular disease. PMID:24705294

  18. Automated melanoma diagnosis system

    NASA Astrophysics Data System (ADS)

    Bischof, Leanne M.; Talbot, H.; Breen, E.; Lovell, D.; Chan, D.; Stone, G.; Menzies, Scott W.; Gutenev, A.; Caffin, R.

    1999-07-01

    The Skin Polarprobe, an automated melanoma diagnosis system, has the potential to greatly improve the chances of early detection of skin cancers and help save the lives of melanoma victims. This paper will describe the development of this device from the initial proof-of-concept phase (Phase I) using digitized slide images, through the first prototype video-based system (Phase II), to the current status of the production prototype system. Because of commercial confidentiality, precise details of each step cannot be given. However, some of the technical difficulties at each step will be described and some general points about how to overcome them will be discussed. Many of these comments will be generic to any imaging application.

  19. Diagnosis of subclinical rickets.

    PubMed Central

    Pettifor, J M; Isdale, J M; Sahakian, J; Hansen, J D

    1980-01-01

    44 randomly selected infants under age one year with suspected lower respiratory infections were investigated for the presence of subclinical rickets. Seven infants had metaphyseal changes at the wrist compatible with a diagnosis of rickets and all of these infants had 25-hydroxy-vitamin D (25-OHD) concentrations less than 12 ng/ml. Serum calcium and phosphorus concentrations were normal in all 44 children. Alkaline phosphatase concentrations did not correlate with the presence of metaphyseal changes. The clinical presence of craniotabes or splaying and loss of definition of the anterior ends of the ribs on x-rays did not correlate with metaphyseal changes at the wrist or with 25-OHD concentrations. An x-ray of the wrist is essential to confirm the presence of subclinical rickets and the at-risk infant can be detected by measuring serum 25-OHD concentrations. PMID:7377839

  20. [Periodontal diagnosis in orthodontics].

    PubMed

    Hourdin, Solenn; Glez, Dominique; Sorel, Olivier

    2010-03-01

    Before any orthodontic treatment can begin, it is essential that the patient's periodontium be in sound condition, capable of responding to the movement of teeth in a healthy fashion. Inspection of the dentition, palpation of tissues, and careful study of adequate X-Rays are all necessary for establishing a diagnosis, but review of the depth of gingival pockets with periodontal probes is the key procedure for avoiding blunders in treatment. After periodontal health has been validated, it is vital that orthodontists determine the patient's periodontal biotype by clinical observation and periodontal probing and assess the quality of the gingival attachments of the teeth that will be affected by the expansion forces of treatment. The ensemble of these criteria will dictate what treatment paths and forces the orthodontist will employ. PMID:20359444

  1. 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.

  2. Rapid diagnosis of sepsis

    PubMed Central

    Bloos, Frank; Reinhart, Konrad

    2014-01-01

    Fast and appropriate therapy is the cornerstone in the therapy of sepsis. However, the discrimination of sepsis from non-infectious causes of inflammation may be difficult. Biomarkers have been suggested to aid physicians in this decision. There is currently no biochemical technique available which alone allows a rapid and reliable discrimination between sepsis and non-infectious inflammation. Procalcitonin (PCT) is currently the most investigated biomarker for this purpose. C-reactive protein and interleukin 6 perform inferior to PCT in most studies and their value in diagnosing sepsis is not defined. All biomarkers including PCT are also released after various non-infectious inflammatory impacts. This shortcoming needs to be taken into account when biomarkers are used to aid the physician in the diagnosis of sepsis. Polymerase chain reaction (PCR) based pathogen detection may improve time to adequate therapy but cannot rule out the presence of infection when negative. PMID:24335467

  3. 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

  4. Basics of DNA biosensors and cancer diagnosis.

    PubMed

    Sohrabi, Nasrin; Valizadeh, Alireza; Farkhani, Samad Mussa; Akbarzadeh, Abolfazl

    2014-11-13

    The human genome is exposed to mutations during the life cycle because of many types of changes in the DNA. Viruses, radiation, transposons, mutagenic chemicals, or any errors that happen during DNA replication or the meiotic process in the cell, may cause the mutation. Many mutations have no effect on phenotype or health, while some mutations cause crucial diseases such as cancer or cardiac diseases; therefore, a better understanding of the effects of mutation on phenotype is a very important part of genetic studies. Biosensors based on DNA, RNA, and peptide nucleic acids are the most sensitive tools, due to a strong pairing of lined up nucleotide strands between bases in their complementary parts. These methods can provide information to assist clinicians in making successful treatment decisions and increase the patient survival rate. In this review, we discuss DNA biosensors based on peptide nucleic acids that have an important role in cancer diagnosis. PMID:25391843

  5. Genetics Home Reference: What is genetic testing?

    MedlinePLUS

    ... Work Mutations and Health Inheritance Consultation Testing Therapy Human Genome Project Genomic Research Next Handbook > Genetic Testing > What is genetic testing? Genetic testing is a type of ... National Human Genome Research Institute provides an overview of this ...

  6. Diagnosis of heel pain.

    PubMed

    Tu, Priscilla; Bytomski, Jeffrey R

    2011-10-15

    Heel pain is a common presenting symptom in ambulatory clinics. There are many causes, but a mechanical etiology is most common. Location of pain can be a guide to the proper diagnosis. The most common diagnosis is plantar fasciitis, a condition that leads to medial plantar heel pain, especially with the first weight-bearing steps in the morning and after long periods of rest. Other causes of plantar heel pain include calcaneal stress fracture (progressively worsening pain following an increase in activity level or change to a harder walking surface), nerve entrapment (pain accompanied by burning, tingling, or numbness), heel pad syndrome (deep, bruise-like pain in the middle of the heel), neuromas, and plantar warts. Achilles tendinopathy is a common condition that causes posterior heel pain. Other tendinopathies demonstrate pain localized to the insertion site of the affected tendon. Posterior heel pain can also be attributed to a Haglund deformity, a prominence of the calcaneus that may cause bursa inflammation between the calcaneus and Achilles tendon, or to Sever disease, a calcaneal apophysitis in children. Medial midfoot heel pain, particularly with continued weight bearing, may be due to tarsal tunnel syndrome, which is caused by compression of the posterior tibial nerve as it courses through the flexor retinaculum, medial calcaneus, posterior talus, and medial malleolus. Sinus tarsi syndrome occurs in the space between the calcaneus, talus, and talocalcaneonavicular and subtalar joints. The syndrome manifests as lateral midfoot heel pain. Differentiating among causes of heel pain can be accomplished through a patient history and physical examination, with appropriate imaging studies, if indicated. PMID:22010770

  7. RNA genetics

    SciTech Connect

    Domingo, E. (Instituto de Biologia Molecular, Facultad de Ciencias, Universidad Autonoma de Madrid, Canto Blanco, Madrid (ES)); Holland, J.J. (California Univ., San Diego, La Jolla, CA (USA). Dept. of Biology); Ahlquist, P. (Wisconsin Univ., Madison, WI (USA). 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.

  8. Genetic Drift

    NSDL National Science Digital Library

    Scott Cooper

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

  9. 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)

  10. Understanding Genetics

    NSDL National Science Digital Library

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

  11. Genetic Counseling Program Information

    E-print Network

    Berdichevsky, Victor

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

  12. Pathophysiology, diagnosis, and treatment of mineralocorticoid disorders.

    PubMed

    Magill, Steven B

    2014-07-01

    The renin-angiotensin-aldosterone system (RAAS) is a major regulator of blood pressure control, fluid, and electrolyte balance in humans. Chronic activation of mineralocorticoid production leads to dysregulation of the cardiovascular system and to hypertension. The key mineralocorticoid is aldosterone. Hyperaldosteronism causes sodium and fluid retention in the kidney. Combined with the actions of angiotensin II, chronic elevation in aldosterone leads to detrimental effects in the vasculature, heart, and brain. The adverse effects of excess aldosterone are heavily dependent on increased dietary salt intake as has been demonstrated in animal models and in humans. Hypertension develops due to complex genetic influences combined with environmental factors. In the last two decades, primary aldosteronism has been found to occur in 5% to 13% of subjects with hypertension. In addition, patients with hyperaldosteronism have more end organ manifestations such as left ventricular hypertrophy and have significant cardiovascular complications including higher rates of heart failure and atrial fibrillation compared to similarly matched patients with essential hypertension. The pathophysiology, diagnosis, and treatment of primary aldosteronism will be extensively reviewed. There are many pitfalls in the diagnosis and confirmation of the disorder that will be discussed. Other rare forms of hyper- and hypo-aldosteronism and unusual disorders of hypertension will also be reviewed in this article. PMID:24944031

  13. [Clinical importance and diagnosis of halitosis].

    PubMed

    Akos, Nagy; Zsolt, Brugoviczky; Péter, Novák; Gábor, Nagy

    2012-09-01

    The origin of halitosis comes from the Latin word "halitus" meaning 'breath, exhaled air', and in the Hungarian terminology it means bad and smelly breath. The human body emits a number of volatile molecules, which have a peculiar odour. Their presence is influenced by several factors, such as genetic, nutritional and psychological factors. Since bad breath belongs to taboo subjects, halitosis can often lead to social isolation. To determine the incidence of halitosis, an exact diagnosis is needed which sometimes predestinates the possible treatment as well. Investigators estimate the incidence about 50% in the whole population. The male/female ratio is the same and the incidence is growing with age. The diagnosis can be genuine halitosis, pseudo halitosis and halitophobia. We can divide the genuine type into physiological and pathophysiological subtypes. The cause of the halitosis usually can be found in the oral cavity. The volatile sulfur compounds (VSC) produced by some of the oral bacteria are responsible for its development. Only 10% of the causes are extraoral, mostly inflammation of airways or gastrointestinal disorders. The judgment of halitosis is based on three objective methods: the organoleptic, the sulphide monitoring and the gas cromatography methods. Since the origin of the halitosis is mainly the oral cavity, dentists should treat them. Beyond the dental treatments the enhancement of the oral hygiene, the continuous motivation and monitoring are also very important, such as the use of tongue cleansing and special anti-malodour rinses. PMID:23240492

  14. 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

  15. Diagnosis and management of polycystic liver disease.

    PubMed

    Gevers, Tom J G; Drenth, Joost P H

    2013-02-01

    Polycystic liver disease (PLD) is arbitrarily defined as a liver that contains >20 cysts. The condition is associated with two genetically distinct diseases: as a primary phenotype in isolated polycystic liver disease (PCLD) and as an extrarenal manifestation in autosomal dominant polycystic kidney disease (ADPKD). Processes involved in hepatic cystogenesis include ductal plate malformation with concomitant abnormal fluid secretion, altered cell-matrix interaction and cholangiocyte hyperproliferation. PLD is usually a benign disease, but can cause debilitating abdominal symptoms in some patients. The main risk factors for growth of liver cysts are female sex, exogenous oestrogen use and multiple pregnancies. Ultrasonography is very useful for achieving a correct diagnosis of a polycystic liver and to differentiate between ADPKD and PCLD. Current radiological and surgical therapies for symptomatic patients include aspiration-sclerotherapy, fenestration, segmental hepatic resection and liver transplantation. Medical therapies that interact with regulatory mechanisms controlling expansion and growth of liver cysts are under investigation. Somatostatin analogues are promising; several clinical trials have shown that these drugs can reduce the volume of polycystic livers. The purpose of this Review is to provide an update on the diagnosis and management of PLD with a focus on literature published in the past 4 years. PMID:23296249

  16. Is gene discovery research or diagnosis?

    PubMed

    Samuels, Mark E; Orr, Andrew; Guernsey, Duane L; Dooley, Kent; Riddell, Christie; Hodgkinson, Kathy; Ludman, Mark; Pullman, Daryl

    2008-06-01

    The criteria that distinguish human genetic research from clinical molecular diagnosis are frequently practical rather than theoretical. They are driven by the availability and costs of the relevant technologies and the systemic level of scientific fluency in interpreting laboratory results. The guiding principle in the practice of medicine is the primacy of patient care. In the service of this overarching goal the defining characteristic of clinical diagnosis is the definition of the disease entity, even when no immediate treatment is possible. For heritable disorders caused by single-gene defects, identifying the putative causal variant is the goal of molecular diagnostics. Current technologies, costs, and standards of institutional infrastructure have not typically permitted novel gene discovery to be performed within the realm of the clinical laboratory. Discovery is usually funded by self-defined research organizations and carried out by self-defined research personnel with the primary intent of publishing findings in research journals. However, exponential improvements in technological capabilities and the concurrent decline in associated costs seem poised to recast this landscape, bringing to clinical medicine some activities now considered research. Even whole genome resequencing of individual patient DNA is within clinical reach in the foreseeable future. PMID:18496224

  17. Molecular Cytogenetic Diagnosis and Somatic Genome Variations

    PubMed Central

    Vorsanova, S.G; Yurov, Y.B.; Soloviev, I.V.; Iourov, I.Y.

    2010-01-01

    Human molecular cytogenetics integrates the knowledge on chromosome and genome organization at the molecular and cellular levels in health and disease. Molecular cytogenetic diagnosis is an integral part of current genomic medicine and is the standard of care in medical genetics and cytogenetics, reproductive medicine, pediatrics, neuropsychiatry and oncology. Regardless numerous advances in this field made throughout the last two decades, researchers and practitioners who apply molecular cytogenetic techniques may encounter several problems that are extremely difficult to solve. One of them is undoubtedly the occurrence of somatic genome and chromosome variations, leading to genomic and chromosomal mosaicism, which are related but not limited to technological and evaluative limitations as well as multiplicity of interpretations. More dramatically, current biomedical literature almost lacks descriptions, guidelines or solutions of these problems. The present article overviews all these problems and gathers those exclusive data acquired from studies of genome and chromosome instability that is relevant to identification and interpretations of this fairly common cause of somatic genomic variations and chromosomal mosaicism. Although the way to define pathogenic value of all the intercellular variations of the human genome is far from being completely understood, it is possible to propose recommendations on molecular cytogenetic diagnosis and management of somatic genome variations in clinical population. PMID:21358989

  18. Molecular cytogenetic diagnosis and somatic genome variations.

    PubMed

    Vorsanova, S G; Yurov, Y B; Soloviev, I V; Iourov, I Y

    2010-09-01

    Human molecular cytogenetics integrates the knowledge on chromosome and genome organization at the molecular and cellular levels in health and disease. Molecular cytogenetic diagnosis is an integral part of current genomic medicine and is the standard of care in medical genetics and cytogenetics, reproductive medicine, pediatrics, neuropsychiatry and oncology. Regardless numerous advances in this field made throughout the last two decades, researchers and practitioners who apply molecular cytogenetic techniques may encounter several problems that are extremely difficult to solve. One of them is undoubtedly the occurrence of somatic genome and chromosome variations, leading to genomic and chromosomal mosaicism, which are related but not limited to technological and evaluative limitations as well as multiplicity of interpretations. More dramatically, current biomedical literature almost lacks descriptions, guidelines or solutions of these problems. The present article overviews all these problems and gathers those exclusive data acquired from studies of genome and chromosome instability that is relevant to identification and interpretations of this fairly common cause of somatic genomic variations and chromosomal mosaicism. Although the way to define pathogenic value of all the intercellular variations of the human genome is far from being completely understood, it is possible to propose recommendations on molecular cytogenetic diagnosis and management of somatic genome variations in clinical population. PMID:21358989

  19. Diagnosis of Wilson's disease in an asymptomatic sibling by DNA linkage analysis

    Microsoft Academic Search

    Theresia Maier-Dobersberger; Christine Mannhalter; Sabine Rack; Gerhard Granditsch; Klaus Kaserer; Lisa Korninger; Petra Steindl; Alfred Gangl; Peter Ferenci

    1995-01-01

    The molecular genetic diagnosis of Wilson's disease in the 5-year-old sister of a patient with Wilson's disease is reported. The girl was clinically free of disease and had no conventional biochemical markers of Wilson's disease (i.e., normal ceruloplasmin, normal copper in the serum, normal 24-hour urinary copper excretion). Diagnosis with restriction fragment length polymorphisms and a nonradioactive polymerase chain reaction-based

  20. A new condition monitoring and fault diagnosis system of induction motors using artificial intelligence algorithms

    Microsoft Academic Search

    Tian Han; Bo-Suk Yang; Jong Moon Lee

    2005-01-01

    In this paper, a condition monitoring and fault diagnosis system for induction motors is proposed by integrating artificial intelligence algorithms: principal component analysis (PCA), genetic algorithm (GA) and an artificial neural network (ANN). As main diagnosis media of fault motor, three-direction vibration signals and three-phase stator current signals are selected to measure. Multi-sensor measurement results in lots of data transfer