Sample records for genetic diagnosis pgd

  1. Preimplantation Genetic Diagnosis (PGD) in France

    Microsoft Academic Search

    Yves J. R. Menezo; René Frydman; Nelly Frydman

    2004-01-01

    In vitro fertilization is strongly regulated in France. An agreement is needed for the clinicians and the embryologists; and the activity is under the control of CNMBRDP, a governmental commission. PGD is even more controlled; an agreement is needed for embryo biopsy and for genetic\\/FISH testing. Only three centers are allowed to perform PGD. All the agreements are given for

  2. Public, expert and patients' opinions on preimplantation genetic diagnosis (PGD) in Germany.

    PubMed

    Krones, Tanja; Schlüter, Elmar; Manolopoulos, Konstantin; Bock, Karin; Tinneberg, Hans-Rudolf; Koch, Manuela C; Lindner, Martin; Hoffmann, Georg F; Mayatepek, Ertan; Huels, Gerd; Neuwohner, Elke; El Ansari, Susan; Wissner, Thomas; Richter, Gerd

    2005-01-01

    The regulation of reproductive medicine technologies differs significantly among Western industrialized countries. In Germany, preimplantation genetic diagnosis (PGD) is prohibited due to the Embryo Protection Act, which came into force in 1991. In the last 5 years, this prohibition has been vigorously debated. In the present studies, which are part of the German research programme on ethical implications of the Human Genome Project, representative surveys were undertaken to assess the attitudes on PGD in the general population (n = 1017), five relevant expert groups (n = 879), high genetic risk couples (n = 324) and couples undergoing IVF (n = 108). All groups surveyed clearly favoured allowing PGD in Germany. Compared with the results of recently conducted population surveys in the UK and the USA, where PGD is already carried out, public approval of PGD does not differ significantly. The influence of restrictive biopolitics on the apparently liberal public opinion towards new reproductive technology seems to be marginal according to the present data, which should carefully be considered in the ongoing legislation process on human reproduction. PMID:15705307

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

    PubMed

    Whittaker, Andrea

    2015-09-01

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

  4. Preimplantation genetic diagnosis and ‘savior siblings’

    Microsoft Academic Search

    B. M. Dickens

    2005-01-01

    From its emergence, preimplantation genetic diagnosis (PGD) has been opposed by religious, feminist, and disability-rights advocates. PGD has developed, however, to extend beyond genetic diagnosis of embryos to diagnose chromosomal abnormalities. Evidence shows that PGD is safe, children born after in vitro fertilization (IVF) and PGD having no higher rate of birth defects than children of normal pregnancies. Laws may

  5. Social welfare, genetic welfare? Boundary-work in the IVF\\/PGD clinic

    Microsoft Academic Search

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

    2006-01-01

    Through the lens of the ‘welfare of the child’ assessment, this paper explores how staff working in the area of in vitro fertilisation and preimplantation genetic diagnosis (IVF\\/PGD) balance reflexive relations of legitimacy and accountability between the public and private spheres, and between medicine, the citizen and the state. The wider research of which this analysis is a part uses

  6. Preimplantation genetic diagnosis: technology and clinical applications.

    PubMed

    Swanson, Amy; Strawn, Estil; Lau, Eduardo; Bick, David

    2007-05-01

    Preimplantation genetic diagnosis (PGD) is a method by which embryos formed through in vitro fertilization (IVF) can be tested for single-gene disorders or chromosome abnormalities prior to embryo transfer. This enables couples to significantly improve their chances of having a healthy child. PGD is an important addition to conventional prenatal diagnosis for genetic disorders. PGD is a complex combination of various technologies that requires close collaboration of a team of specialists for optimal patient care. This review article will cover patient management, assisted reproductive technologies including IVF and PGD as well as indications for PGD. Clinical vignettes from The Froedtert Hospital and Medical College of Wisconsin Reproductive Medicine Clinic PGD Program will be presented, including the first single-gene disorder PGD performed in Wisconsin. These vignettes highlight the importance of a detailed family history, use of PGD for cases of recurrent miscarriage, and the use of PGD for spinal muscular atrophy. PMID:17642353

  7. 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

  8. PGD in female carriers of balanced Robertsonian and reciprocal translocations by first polar body analysis

    Microsoft Academic Search

    M. Durban; J. Benet; M. Boada; E. Fernandez; J. Ma; J. F. Sanchez-Garcia; A. Pujol; J. Egozcue; J. Navarro

    2001-01-01

    Preimplantation genetic diagnosis (PGD) using the first polar body (1PB) is a modality of PGD that can be used when the woman is the carrier of a genetic disease or of a balanced chromosomal reorganization. PGD using 1PB biopsy in carriers of balanced chromosome reorganizations has not become generalized. Here, we describe our experience based on the analysis of unfertilized

  9. Social representations of stem cell research and preimplantation genetic diagnosis

    Microsoft Academic Search

    BA Jones; CA McMahon

    2003-01-01

    The study examined public thinking about stem cell research and preimplantation genetic diagnosis (PGD) using social representation theory. Social representation theory is concerned with the movement of scientific knowledge from the realm of the specialist into lay knowledge. Participants were interviewed and the data analysed qualitatively. Three social representations were found for both stem cell research and PGD. For stem

  10. Birth of a healthy boy after a double factor PGD in a couple carrying a genetic disease and at risk for aneuploidy: case report.

    PubMed

    Obradors, Albert; Fernández, Esther; Oliver-Bonet, Maria; Rius, Mariona; de la Fuente, Alfonso; Wells, Dagan; Benet, Jordi; Navarro, Joaquima

    2008-08-01

    Preimplantation genetic diagnosis (PGD) for monogenic diseases is widely applied, allowing the transfer to the uterus of healthy embryos. PGD is also employed for the detection of chromosome abnormalities for couples at high risk of producing aneuploid embryos, such as advanced maternal (>35 years). A significant number of patients requesting PGD for monogenic diseases are also indicated for chromosome testing. We optimized and clinically applied a PGD protocol permitting both cytogenetic and molecular genetic analysis. A couple, carriers of two cystic fibrosis (CF) mutations (c.3849 + 10 KbC > T and c.3408C > A) with a maternal age of 38 years and two previously failed IVF-PGD cycles, was enrolled in the study. After ovarian stimulation, six oocytes were obtained. To detect abnormalities for all 23 chromosomes of the oocyte, the first polar body (1PB) was biopsied from five of the oocytes and analyzed using comparative genomic hybridization (CGH). CGH analysis showed that 1PB 1 and 1PB 4 were aneuploid (22X,-9,-13,+19 and 22X,-6, respectively), while 1PB 2, 1PB 3 and 1PB 6 were euploid. Blastomere biopsy was only applicable on embryos formed from Oocyte 3 and Oocyte 6. After whole-genome amplification with multiple displacement amplification, a multiplex PCR, amplifying informative short tandem repeats (D7S1799; D7S1817) and DNA fragments encompassing the mutation sites, was performed. MiniSequencing was applied to directly detect each mutation. Genetic diagnosis showed that Embryo 6 was affected by CF and Embryo 3 carried only the c.3849 + 10 KbC > T mutation. Embryo 3 was transferred achieving pregnancy and a healthy boy was born. This strategy may lead to increased pregnancy rates by allowing preferential transfer of euploid embryos. PMID:18523000

  11. Ethics and the future of preimplantation genetic diagnosis.

    PubMed

    Robertson, John A

    2005-03-01

    The future growth of preimplantation genetic diagnosis (PGD) will depend on refinements in genetic knowledge and genetic analysis of blastomeres. Equally important, however, is an acceptance of the ethical legitimacy of parents using technologies to select genetic traits of offspring. Objections based on embryo status, the giftedness of reproduction, eugenics, and protecting the child's welfare are not convincing grounds to oppose most uses of PGD. Whether PGD should be accepted for new medical or non-medical uses should depend upon a careful assessment of the proposed use's importance to the person or couple requesting it, and the harmful effects, if any, which it might cause. Such an approach leads to the conclusion that most new medical uses of PGD and some non-medical uses should be permitted. PMID:15820017

  12. Pandora's box: ethics of PGD for inherited risk of late-onset disorders

    Microsoft Academic Search

    Ray Noble; Gulam Bahadur; Mohammad Iqbal; Arnab Sanyal

    2008-01-01

    Until recently, the primary use of preimplantation genetic diagnosis (PGD) has been the selection of embryos to avoid lethal or debilitating gene mutations or abnormal chromosome complement. PGD can be used to reduce the risk of transferring to the uterus an embryo with Down syndrome, and parents who are carriers of severe genetic diseases may choose to avoid having children

  13. 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

  14. Preimplantation genetic diagnosis guided by single-cell genomics

    PubMed Central

    2013-01-01

    Preimplantation genetic diagnosis (PGD) aims to help couples with heritable genetic disorders to avoid the birth of diseased offspring or the recurrence of loss of conception. Following in vitro fertilization, one or a few cells are biopsied from each human preimplantation embryo for genetic testing, allowing diagnosis and selection of healthy embryos for uterine transfer. Although classical methods, including single-cell PCR and fluorescent in situ hybridization, enable PGD for many genetic disorders, they have limitations. They often require family-specific designs and can be labor intensive, resulting in long waiting lists. Furthermore, certain types of genetic anomalies are not easy to diagnose using these classical approaches, and healthy offspring carrying the parental mutant allele(s) can result. Recently, state-of-the-art methods for single-cell genomics have flourished, which may overcome the limitations associated with classical PGD, and these underpin the development of generic assays for PGD that enable selection of embryos not only for the familial genetic disorder in question, but also for various other genetic aberrations and traits at once. Here, we discuss the latest single-cell genomics methodologies based on DNA microarrays, single-nucleotide polymorphism arrays or next-generation sequence analysis. We focus on their strengths, their validation status, their weaknesses and the challenges for implementing them in PGD. PMID:23998893

  15. Current status of preimplantation genetic diagnosis in Japan

    PubMed Central

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

    2015-01-01

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

  16. 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

  17. 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

  18. 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

  19. FISH for Pre-implantation Genetic Diagnosis

    PubMed Central

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

    2011-01-01

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

  20. Successful polar body-based preimplantation genetic diagnosis for achondroplasia.

    PubMed

    Altarescu, G; Renbaum, P; Brooks P, B; Margalioth, E J; Ben Chetrit, A; Munter, G; Levy-Lahad, E; Eldar-Geva, T

    2008-02-01

    Achondroplasia, the most common form of dwarfism, is a candidate for preimplantation genetic diagnosis (PGD) because a single mutation accounts for almost all cases. Multiplex fluorescent assay including the common G380R mutation in the FGFR3 gene and eight close polymorphic markers was developed. First and second polar bodies (PB) were used for PGD analysis. An affected woman was treated with routine long-protocol ovarian stimulation and puncture. In the first PGD cycle, out of four fertilized oocytes, PB analysis revealed two mutant oocytes, one with total amplification failure of the maternal allele and one with inconclusive results. In the second PGD cycle, 14 oocytes were retrieved following a higher FSH dose and by performing oocyte retrieval and by placing the patient in the anti-Trendelenburg position using abdominal pressure to allow all follicles to be drained. Following PB analysis, two embryos containing the wild-type FGFR3 allele were transferred. This led to an uncomplicated pregnancy and delivery by Caesarean section at week 38 of a healthy boy, carrying the FGFR3 wild-type maternal allele. In conclusion, oocyte retrieval, while difficult in patients with achondroplasia, can be successfully performed. PB analysis is a reliable and sensitive method for PGD for maternal achondroplasia. PMID:18284886

  1. Preimplantation genetic diagnosis for early-onset torsion dystonia

    Microsoft Academic Search

    S Rechitsky; O Verlinsky; A Kuliev; S Ozen; K Laziuk; R Beck; N Gleicher; Y Verlinsky

    2004-01-01

    Early-onset primary torsion dystonia (DYT1) is the most severe and common form of hereditary movement disorders, characterized by sustained twisting contractures that begin in childhood, which is caused in majority of cases by a 3-bp deletion of the DYT1 gene on chromosome 9q34 at the heterozygote state. As there is no effective treatment of this disease, preimplantation genetic diagnosis (PGD)

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

    PubMed

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

    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 married to her first cousin with four affected children was referred for PGD. The hyperinsulinism disease was caused by a novel homozygous mutation in the KCNJ11 gene, an arginine 301 to proline (R301P) substitution.PGD was achieved by whole genome amplification followed by mutation detection combined with short tandem repeat identifier analysis in the first cycle and with haplotyping in the second cycle. The first and second cycles resulted in the births of healthy twin girls and a boy, respectively. As far as is known, this is the first application of PGD to hyperinsulinism. A feasible strategy including whole genome amplification followed by direct mutation detection combined with haplotyping is described.Utilizing haplotyping increases the efficiency of PGD diagnosis as well as confirming the genetic diagnosis. It reveals the parental origin of each inherited chromosome. PMID:21115269

  3. Intracytoplasmic sperm injection combined with preimplantation genetic diagnosis for the prevention of recurrent gestational trophoblastic disease

    Microsoft Academic Search

    Benjamin E. Reubinoff; Aby Lewin; Marion Verner; Anat Safran; Joseph G. Schenker; Dvorah Abeliovich

    3To whom correspondence should be addressed diploid 46,XX complement. Alternatively, 16% of complete A strategy for the prevention of repeated molar pregnancies moles originate from a dispermic fertilization, and are therefore by using intracytoplasmic sperm injection (ICSI) coupled diploid (46,XX or 46,XY) heterozygous (Wake et al., 1987; with preimplantation genetic diagnosis (PGD) with fluores- Lawler et al., 1991). The karyotype

  4. 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

  5. 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

  6. Preimplantation genetic diagnosis for early-onset torsion dystonia.

    PubMed

    Rechitsky, S; Verlinsky, O; Kuliev, A; Ozen, S; Laziuk, K; Beck, R; Gleicher, N; Verlinsky, Y

    2004-02-01

    Early-onset primary torsion dystonia (DYT1) is the most severe and common form of hereditary movement disorders, characterized by sustained twisting contractures that begin in childhood, which is caused in majority of cases by a 3-bp deletion of the DYT1 gene on chromosome 9q34 at the heterozygote state. As there is no effective treatment of this disease, preimplantation genetic diagnosis (PGD) may be a useful option for at-risk couples to establish an DYT1 mutation-free pregnancy. PGD was performed for two obligate carriers of the DYT1 3-bp deletion, using blastomere testing to preselect the mutation-free embryos, based on mutation analysis with simultaneous testing of the three closely linked markers, D9S62, D9S63 and ASS. Of 19 tested blastomeres in three cycles, 17 had conclusive information about the mutation and linked markers, of which eight were predicted to be free of 3-bp deletion. Six of these embryos were transferred back to patients, two in each cycle, yielding singleton DYT1 3-bp deletion-free clinical pregnancies in two. One of these pregnancies was terminated due to severe anencephaly and the other resulted in birth of a mutation-free child. This is the first PGD for primary torsion dystonia, providing an alternative for those at-risk couples who cannot accept prenatal diagnosis and termination of pregnancy as an option for avoiding early onset torsion dystonia. PMID:14989804

  7. Pandora's box: ethics of PGD for inherited risk of late-onset disorders.

    PubMed

    Noble, Ray; Bahadur, Gulam; Iqbal, Mohammad; Sanyal, Arnab

    2008-01-01

    Until recently, the primary use of preimplantation genetic diagnosis (PGD) has been the selection of embryos to avoid lethal or debilitating gene mutations or abnormal chromosome complement. PGD can be used to reduce the risk of transferring to the uterus an embryo with Down syndrome, and parents who are carriers of severe genetic diseases may choose to avoid having children with these debilitating genetic conditions. The use of PGD is now being extended to include gene mutations that increase the risk of late-onset disorders such as breast and ovarian cancer. This paper argues for caution in advocating reproductive methods that are costly, have a limited chance of success, and for which the long-term outcome is unknown. Counselling should allow women a true choice of declining the option of PGD without recrimination, feelings of guilt or social pressure. There is concern that the Human Fertilisation and Embryology Authority has approved extension of PGD to late-onset multifactorial diseases without clear guidelines for its use. Guidelines for embryo selection should be revised to deal with potential conflict between reproductive success and genetic screening for disorders that do not profoundly affect the embryo or the children. PMID:18983739

  8. Parental mosaicism is a pitfall in preimplantation genetic diagnosis of dominant disorders

    PubMed Central

    Steffann, Julie; Michot, Caroline; Borghese, Roxana; Baptista-Fernandes, Marcia; Monnot, Sophie; Bonnefont, Jean-Paul; Munnich, Arnold

    2014-01-01

    PCR amplification on single cells is prone to allele drop-out (PCR failure of one allele), a cause of misdiagnosis in preimplantation genetic diagnosis (PGD). Owing to this error risk, PGD usually relies on both direct and indirect genetic analyses. When the affected partner is the sporadic case of a dominant disorder, building haplotypes require spermatozoon or polar body testing prior to PGD, but these procedures are cost and time-consuming. A couple requested PGD because the male partner suffered from a dominant Cowden syndrome (CS). He was a sporadic case, but the couple had a first unaffected child and the non-mutated paternal haplotype was tentatively deduced. The couple had a second spontaneous pregnancy and the fetus was found to carry the at-risk haplotype but not the PTEN mutation. The mutation was present in blood from the affected father, but at low level, confirming the somatic mosaicism. Ignoring the possibility of mosaicism in the CS patient would have potentially led to selection of affected embryos. This observation emphasizes the risk of PGD in families at risk to transmit autosomal-dominant disorder when the affected partner is a sporadic case. PMID:24022303

  9. PGD Synthase and PGD2 in Immune Resposne

    PubMed Central

    Joo, Myungsoo; Sadikot, Ruxana T.

    2012-01-01

    PGD2 is formed from arachidonic acid by successive enzyme reactions: oxygenation of arachidonic acid to PGH2, a common precursor of various prostanoids, catalyzed by cyclooxygenase, and isomerization of PGH2 to PGD2 by PGD synthases (PGDSs). PGD2 can be either pro- or anti-inflammatory depending on disease process and etiology. The anti-inflammatory and immunomodulatory attributes of PGDS/PGD2 provide opportunities for development of novel therapeutic approaches for resistant infections and refractory inflammatory diseases. This paper highlights the role of PGD synthases and PGD2 in immune inflammatory response. PMID:22791937

  10. 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

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

    PubMed Central

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

    2015-01-01

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

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

    Microsoft Academic Search

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

    2012-01-01

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

  13. BRCA1/2 carriers: their childbearing plans and theoretical intentions about having preimplantation genetic diagnosis and prenatal diagnosis

    PubMed Central

    Julian-Reynier, Claire; Fabre, Roxane; Coupier, Isabelle; Stoppa-Lyonnet, Dominique; Lasset, Christine; Caron, Olivier; Mouret-Fourme, Emmanuelle; Berthet, Pascaline; Faivre, Laurence; Frenay, Marc; Gesta, Paul; Gladieff, Laurence; Bouhnik, Anne-Deborah; Protière, Christel; Noguès, Catherine

    2012-01-01

    Purpose: To assess the impact of BRCA1/2 test results on carriers' reproductive decision-making and the factors determining their theoretical intentions about preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND). Methods: Unaffected BRCA1/2 mutation carriers of childbearing age (N = 605; 449 women; 151 men) were included at least 1 year after the disclosure of their test results in a cross-sectional survey nested in a national cohort. Multivariate adjustment was performed on the data obtained in self-administered questionnaires. Results: Response rate was 81.0%. Overall, 32.5% and 50% said that they would undergo PGD/PND, respectively, at a theoretical next pregnancy, whereas only 12.1% found termination of pregnancy (TOP) acceptable. Theoretical intentions toward PGD did not depend on gender/age, but were higher among those with no future childbearing plans (adjusted odds ratio (AOR) 95% confidence interval (CI): 3.5 (1.9–6.4)) and those having fewer relatives with cancer (AOR 1.5 95% CI (1.0–2.3)). Greater TOP acceptability was observed among males and those with lower educational levels; 85.4% of respondents agreed that information about PGD/PND should be systematically delivered with the test results. Conclusions: The closer to reproductive decision-making BRCA1/2 carriers are, i.e., when they are more likely to be making future reproductive plans, the less frequently they intend to have PGD. Carriers' theoretical intentions toward PND are discussed further. PMID:22241105

  14. Perinatal genetics: Diagnosis and treatment

    SciTech Connect

    Porter, I.H.; Hatcher, N.H.; Willey, A.M.

    1986-01-01

    This book consists of six sections, each containing several chapters. Some of the chapter titles are: Prenatal Diagnosis of the Fragile X Syndrome; Prenatal Genetic Diagnosis by Chorionic Villus Sampling; Prenatal Treatment of Biochemical Disorders; H-Y Antigen, Sex Determination and Gender Control; and Environmental Factors and Human Birth Defects: Interpretation of Relative Risks in Clinical Genetics.

  15. Customizing conception: a survey of preimplantation genetic diagnosis and the resulting social, ethical, and legal dilemmas.

    PubMed

    Roberts, Jason C

    2002-07-23

    One in six American couples experience difficulties conceiving a child. With fertility rates at an all time low, the business of treating infertility is booming. However, due to the United States prohibition on government funding for embryonic research, the $4 billion industry of assisted reproductive technologies (ART) has been incompletely monitored and largely removed from oversight. Additionally, due to the fervent abortion debate, in vitro fertilization (IVF) was introduced in the United States without a research phase and procedures have been forced to evolve in the private sector. Thus, the checks and balances on medical innovation that are generally imposed by the federal government for consumer protection are lacking. Decisions about when to go from the laboratory to the clinic are often left solely to the discretion of private physicians. Preimplantation genetic diagnosis (PGD) is just one of many such treatments offered by these clinics. This iBrief examines how, why, and to whom the reproductive procedure of PGD is offered. In addition, it evaluates the prospective effects to society that arise when PGD is used for sex selection and for nontherapeutic or enhancement purposes. Finally, it explores whether and how to regulate PGD in the United States by investigating approaches to policy making that have been adopted by the United Kingdom. PMID:15709286

  16. 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.

  17. Use of preimplantation genetic diagnosis to produce tissue donors: an irreconcilable dichotomy?

    PubMed

    Gavaghan, Colin

    2003-02-01

    In 2002, the Human Fertilisation and Embryology Authority (HFEA) published its decision in the case of Raj and Shahana Hashmi. The couple had sought to use preimplantation genetic diagnosis (PGD) to have a child that could be a viable donor for their son, Zain, who has thalassaemia. The HFEA decided that PGD could, in the present case, go ahead. Later in 2002, the HFEA reached the opposite decision in the superficially similar case of Michelle and Jayson Whitaker. This paper will present a critical overview of the decisions of the HFEA in these two cases, and of the opinions and discussions the HFEA published in support thereof. Although it is acknowledged that the two cases differ to some extent in their facts, it is argued that the difference upon which the HFEA relied is one without ethical significance. PMID:12663958

  18. Live birth after PGD with confirmation by a comprehensive approach (karyomapping) for simultaneous detection of monogenic and chromosomal disorders.

    PubMed

    Natesan, Senthilkumar A; Handyside, Alan H; Thornhill, Alan R; Ottolini, Christian S; Sage, Karen; Summers, Michael C; Konstantinidis, Michalis; Wells, Dagan; Griffin, Darren K

    2014-11-01

    Preimplantation genetic diagnosis (PGD) for monogenic disorders has the drawback of time and cost associated with tailoring a specific test for each couple, disorder, or both. The inability of any single assay to detect the monogenic disorder in question and simultaneously the chromosomal complement of the embryo also limits its application as separate tests may need to be carried out on the amplified material. The first clinical use of a novel approach ('karyomapping') was designed to circumvent this problem. In this example, karyomapping was used to confirm the results of an existing PGD case detecting both chromosomal abnormalities and a monogenic disorder (Smith-Lemli-Opitz [SLO] syndrome) simultaneously. The family underwent IVF, ICSI and PGD, and both polar body and cleavage stage biopsy were carried out. Following whole genome amplification, array comparative genomic hybridisation of the polar bodies and minisequencing and STR analysis of single blastomeres were used to diagnose maternal aneuploidies and SLO status, respectively. This was confirmed, by karyomapping. Unlike standard PGD, karyomapping required no a-priori test development. A singleton pregnancy and live birth, unaffected with SLO syndrome and with no chromosome abnormality, ensued. Karyomapping is potentially capable of detecting a wide spectrum of monogenic and chromosome disorders and, in this context, can be considered a comprehensive approach to PGD. PMID:25154779

  19. Preimplantation genetic diagnosis: its role in prevention of deafness.

    PubMed

    Taneja, M K

    2014-01-01

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

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

    PubMed Central

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

    2007-01-01

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

  1. PGD for hereditary breast and ovarian cancer: the route to universal tests for BRCA1 and BRCA2 mutation carriers.

    PubMed

    Drüsedau, Marion; Dreesen, Jos C; Derks-Smeets, Inge; Coonen, Edith; van Golde, Ron; van Echten-Arends, Jannie; Kastrop, Peter M M; Blok, Marinus J; Gómez-García, Encarna; Geraedts, Joep P; Smeets, Hubert J; de Die-Smulders, Christine E; Paulussen, Aimée D

    2013-12-01

    Preimplantation Genetic Diagnosis (PGD) is a method of testing in vitro embryos as an alternative to prenatal diagnosis with possible termination of pregnancy in case of an affected child. Recently, PGD for hereditary breast and ovarian cancer caused by BRCA1 and BRCA2 mutations has found its way in specialized labs. We describe the route to universal single-cell PGD tests for carriers of BRCA1/2 mutations. Originally, mutation-specific protocols with one or two markers were set up and changed when new couples were not informative. This route of changing protocols was finalized after 2 years with universal tests for both BRCA1 and BRCA2 mutation carriers based on haplotyping of, respectively, 6 (BRCA1) and 8 (BRCA2) microsatellite markers in a multiplex PCR. Using all protocols, 30 couples had a total of 47 PGD cycles performed. Eight cycles were cancelled upon IVF treatment due to hypostimulation. Of the remaining 39 cycles, a total of 261 embryos were biopsied and a genetic diagnosis was obtained in 244 (93%). In 34 of the 39 cycles (84.6%), an embryo transfer was possible and resulted in 8 pregnancies leading to a fetal heart beat per oocyte retrieval of 20.5% and a fetal heart beat per embryonic transfer of 23.5%. The preparation time and costs for set-up and validation of tests are minimized. The informativity of microsatellite markers used in the universal PGD-PCR tests is based on CEPH and deCODE pedigrees, making the tests applicable in 90% of couples coming from these populations. PMID:23531862

  2. Preimplantation genetic diagnosis in an HIV-serodiscordant couple carrier for sickle cell disease: lessons from a case report.

    PubMed

    Gonzalez-Merino, E; Zengbe, V; Vannin, A S; Place, I; Bostan, A; Emiliani, S; Liesnard, C; Goffard, J C; Abramowicz, M; Englert, Y

    2009-03-01

    Since 1999, the Erasme Hospital Fertility Clinic has carried a special programme for patients with HIV seropositivity. The philosophy of the programme is to give access to these patients in a secure environment to the same technological facilities available to any other patients. Many of these patients being native from sub-Saharan countries, they are often sickle cell disease (SCD) carriers, a common autosomal recessive disorder in these regions, and a severe affection in homozygotes. We hereby report, for the first time, the birth of a healthy sickle haemoglobin (HbS) heterozygous baby after preimplantation genetic diagnosis (PGD) for SCD in an HIV-serodiscordant couple of HbS mutation carriers with longstanding infertility. The prospective mother was 35 years old and HIV positive with an undetectable viral load under highly active antiretroviral therapy. One carrier embryo was transferred and resulted in the birth of a healthy HbS carrier baby girl. Despite stimulation difficulties, sometimes described in HIV patients, PGD represents an interesting additional technology, especially in populations where the coexistence of both diseases is frequent. PGD could even be preferred to prenatal diagnosis for couples of HbS carriers if the woman is HIV positive, as invasive prenatal samplings carry a risk of materno-foetal viral transmission. PMID:19054017

  3. Diagnosis and new treatments in genetic neuropathies

    Microsoft Academic Search

    M M Reilly; M E Shy

    2009-01-01

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

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

    PubMed Central

    Ehrich, Kathryn; Williams, Clare; Farsides, Bobbie

    2008-01-01

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

  5. Genetic Issues in the Diagnosis of Dystonias

    PubMed Central

    Petrucci, Simona; Valente, Enza Maria

    2013-01-01

    Dystonias are heterogeneous hyperkinetic movement disorders characterized by involuntary muscle contractions which result in twisting and repetitive movements and abnormal postures. Several causative genes have been identified, but their genetic bases still remain elusive. Primary Torsion Dystonias (PTDs), in which dystonia is the only clinical sign, can be inherited in a monogenic fashion, and many genes and loci have been identified for autosomal dominant (DYT1/TOR1A; DYT6/THAP1; DYT4/TUBB4a; DYT7; DYT13; DYT21; DYT23/CIZ1; DYT24/ANO3; DYT25/GNAL) and recessive (DYT2; DYT17) forms. However most sporadic cases, especially those with late-onset, are likely multifactorial, with genetic and environmental factors interplaying to reach a threshold of disease. At present, genetic counseling of dystonia patients remains a difficult task. Recently non-motor clinical findings in dystonias, new highlights in the pathophysiology of the disease, and the availability of high-throughput genome-wide techniques are proving useful tools to better understand the complexity of PTD genetics. We briefly review the genetic basis of the most common forms of hereditary PTDs, and discuss relevant issues related to molecular diagnosis and genetic counseling. PMID:23596437

  6. Singling out genetic disorders and disease

    PubMed Central

    2010-01-01

    Preimplantation genetic diagnosis (PGD) involves testing of single cells biopsied from oocytes and/or embryos generated in vitro. As only embryos unaffected for a given genetic condition are transferred to the uterus, it avoids prenatal diagnosis and termination of pregnancy. Follow-up data from PGD pregnancies, deliveries and children show an acceptable live birth rate and, so far, no detrimental effects of the procedure have been observed. Of course, the long-term health outcome is currently unknown. PGD was first performed in 1990 and remained an experimental procedure for a number of years. Now, two decades later, it is regarded as an established alternative to prenatal diagnosis: its use has expanded, the range of applications has broadened, and continuous technical progress in single-cell testing has led to high levels of efficiency and accuracy. The current gold standard methods (single-cell multiplex-PCR for monogenic diseases and interphase fluorescence in situ hybridization for chromosomal aberrations) are being replaced by single-cell whole genome amplification and array technology. These generalized methods substantially reduce the pre-PGD workload and allow more automated genome-wide analysis. The implementation of laboratory accreditation schemes brings the field at the same level of routine diagnostics. This article reviews the state of the art and considers indications, accuracy and current technical changes in the field of PGD. PMID:20925967

  7. Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management.

    PubMed

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

    2012-07-01

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

  8. The Performance of Whole Genome Amplification Methods and Next-Generation Sequencing for Pre-Implantation Genetic Diagnosis of Chromosomal Abnormalities.

    PubMed

    Li, Na; Wang, Li; Wang, Hui; Ma, Minyue; Wang, Xiaohong; Li, Yi; Zhang, Wenke; Zhang, Jianguang; Cram, David S; Yao, Yuanqing

    2015-04-20

    Reliable and accurate pre-implantation genetic diagnosis (PGD) of patient's embryos by next-generation sequencing (NGS) is dependent on efficient whole genome amplification (WGA) of a representative biopsy sample. However, the performance of the current state of the art WGA methods has not been evaluated for sequencing. Using low template DNA (15 pg) and single cells, we showed that the two PCR-based WGA systems SurePlex and MALBAC are superior to the REPLI-g WGA multiple displacement amplification (MDA) system in terms of consistent and reproducible genome coverage and sequence bias across the 24 chromosomes, allowing better normalization of test to reference sequencing data. When copy number variation sequencing (CNV-Seq) was applied to single cell WGA products derived by either SurePlex or MALBAC amplification, we showed that known disease CNVs in the range of 3-15 Mb could be reliably and accurately detected at the correct genomic positions. These findings indicate that our CNV-Seq pipeline incorporating either SurePlex or MALBAC as the key initial WGA step is a powerful methodology for clinical PGD to identify euploid embryos in a patient's cohort for uterine transplantation. PMID:25953353

  9. Multiple displacement amplification improves PGD for fragile X syndrome

    Microsoft Academic Search

    P. Burlet; N. Frydman; N. Gigarel; V. Kerbrat; G. Tachdjian; E. Feyereisen; J.-P. Bonnefont; R. Frydman; A. Munnich; J. Steffann

    2006-01-01

    We report an improvement in the PGD test for fragile X syndrome (FXS). Recently, multiple displacement amplification (MDA) has been reported to yield large amounts of DNA from single cells. Taking into account this technique, we developed a new PGD test for FXS, enabling combined analysis of linked polymorphic markers with the study of the non-expanded CGG repeat. Single cell

  10. Translational Genetics for Diagnosis of Human Disorders of Sex Development

    PubMed Central

    Baxter, Ruth M.; Vilain, Eric

    2015-01-01

    Disorders of sex development (DSDs) are congenital conditions with discrepancies between the chromosomal, gonadal, and phenotypic sex of the individual. Such disorders have historically been difficult to diagnose and cause great stress to patients and their families. Genetic analysis of human samples has been instrumental in elucidating the molecules and pathways involved in the development of the bipotential gonad into a functioning testis or ovary. However, many DSD patients still do not receive a genetic diagnosis. New genetic and genomic technologies are expanding our knowledge of the underlying mechanism of DSDs and opening new avenues for clinical diagnosis. We review the genetic technologies that have elucidated the genes that are well established in sex determination in humans, discuss findings from more recent genomic technologies, and propose a new paradigm for clinical diagnosis of DSDs. PMID:23875799

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

    PubMed

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

    1991-02-01

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

  12. Prospect of preimplantation genetic diagnosis for heritable mitochondrial DNA diseases

    Microsoft Academic Search

    Nicola L. Dean; Brendan J. Battersby; Asangla Ao; Roger G. Gosden; Seang LinTan; Eric A. Shoubridge

    2003-01-01

    To perform preimplantation genetic diagnosis for women carrying heteroplasmic mitochondrial DNA (mtDNA) mutations, it is necessary to ensure that the proportion of mutant mtDNA diagnosed in the biopsied cell gives an accurate indication of the mutant load in the remaining embryo. A heteroplasmic mouse model, carrying NZB and BALB mtDNA genotypes, was used to study the relative proportions of each

  13. 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.

  14. PGD2-CRTH2 Pathway Promotes Tubulointerstitial Fibrosis

    PubMed Central

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

    2012-01-01

    Urinary excretion of lipocalin-type PGD2 synthase (L-PGDS), which converts PG H2 to PGD2, increases in early diabetic nephropathy. In addition, L-PGDS expression in the tubular epithelium increases in adriamycin-induced nephropathy, suggesting that locally produced L-PGDS may promote the development of CKD. In this study, we found that L-PGDS–derived PGD2 contributes to the progression of renal fibrosis via CRTH2-mediated activation of Th2 lymphocytes. In a mouse model, the tubular epithelium synthesized L-PGDS de novo after unilateral ureteral obstruction (UUO). L-PGDS-knockout mice and CRTH2-knockout mice both exhibited less renal fibrosis, reduced infiltration of Th2 lymphocytes into the cortex, and decreased production of the Th2 cytokines IL-4 and IL-13. Furthermore, oral administration of a CRTH2 antagonist, beginning 3 days after UUO, suppressed the progression of renal fibrosis. Ablation of IL-4 and IL-13 also ameliorated renal fibrosis in the UUO kidney. Taken together, these data suggest that blocking the activation of CRTH2 by PGD2 might be a strategy to slow the progression of renal fibrosis in CKD. PMID:22997255

  15. PGD2-CRTH2 pathway promotes tubulointerstitial fibrosis.

    PubMed

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

    2012-11-01

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

  16. 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

  17. 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

  18. 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

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

    PubMed Central

    Nicolás, Pilar

    2007-01-01

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

  1. The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation.

    PubMed

    Moniot, Brigitte; Declosmenil, Faustine; Barrionuevo, Francisco; Scherer, Gerd; Aritake, Kosuke; Malki, Safia; Marzi, Laetitia; Cohen-Solal, Anne; Georg, Ina; Klattig, Jürgen; Englert, Christoph; Kim, Yuna; Capel, Blanche; Eguchi, Naomi; Urade, Yoshihiro; Boizet-Bonhoure, Brigitte; Poulat, Francis

    2009-06-01

    Activation by the Y-encoded testis determining factor SRY and maintenance of expression of the Sox9 gene encoding the central transcription factor of Sertoli cell differentiation are key events in the mammalian sexual differentiation program. In the mouse XY gonad, SOX9 upregulates Fgf9, which initiates a Sox9/Fgf9 feedforward loop, and Sox9 expression is stimulated by the prostaglandin D2 (PGD2) producing lipocalin prostaglandin D synthase (L-PGDS, or PTDGS) enzyme, which accelerates commitment to the male pathway. In an attempt to decipher the genetic relationships between Sox9 and the L-Pgds/PGD2 pathway during mouse testicular organogenesis, we found that ablation of Sox9 at the onset or during the time window of expression in embryonic Sertoli cells abolished L-Pgds transcription. By contrast, L-Pgds(-/-) XY embryonic gonads displayed a reduced level of Sox9 transcript and aberrant SOX9 protein subcellular localization. In this study, we demonstrated genetically that the L-Pgds/PGD2 pathway acts as a second amplification loop of Sox9 expression. Moreover, examination of Fgf9(-/-) and L-Pgds(-/-) XY embryonic gonads demonstrated that the two Sox9 gene activity amplifying pathways work independently. These data suggest that, once activated and maintained by SOX9, production of testicular L-PGDS leads to the accumulation of PGD2, which in turn activates Sox9 transcription and nuclear translocation of SOX9. This mechanism participates together with FGF9 as an amplification system of Sox9 gene expression and activity during mammalian testicular organogenesis. PMID:19429785

  2. 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

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

    PubMed

    Boileau, C; Collod, G; Bonnet, D

    1997-12-01

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

  4. 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

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

    PubMed Central

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

    2014-01-01

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

  6. Imposing genetic diversity.

    PubMed

    Sparrow, Robert

    2015-06-01

    The idea that a world in which everyone was born "perfect" would be a world in which something valuable was missing often comes up in debates about the ethics of technologies of prenatal testing and preimplantation genetic diagnosis (PGD). This thought plays an important role in the "disability critique" of prenatal testing. However, the idea that human genetic variation is an important good with significant benefits for society at large is also embraced by a wide range of figures writing in the bioethics literature, including some who are notoriously hostile to the idea that we should not select against disability. By developing a number of thought experiments wherein we are to contemplate increasing genetic diversity from a lower baseline in order to secure this value, I argue that this powerful intuition is more problematic than is generally recognized, especially where the price of diversity is the well-being of particular individuals. PMID:26030484

  7. Diagnosis of Wilson Disease in Young Children: Molecular Genetic Testing and a Paradigm Shift from the Laboratory Diagnosis

    PubMed Central

    2012-01-01

    Wilson disease (WD) is an autosomal recessive disorder of copper metabolism that results in accumulation of copper primarily in the liver, brain and cornea. Mutations in the WD gene, ATP7B, cause failure of copper excretion from hepatocyte into bile and a defective synthesis of ceruloplasmin. More than 500 mutations are now recognized, scattered throughout the ATP7B gene. Since WD has protean clinical presentations, awareness of WD in clinical practice is important for the early diagnosis and prevention of accumulated copper toxicity. Molecular genetic testing is playing an increasingly important role in the diagnosis of WD in uncertain cases and family screening. Siblings should be screened for WD once an index case has been diagnosed. Discrimination of heterozygotes from asymptomatic patients is essential to avoid inappropriate lifelong therapy for heterozygotes. Genetic testing, either by haplotype analysis or by mutation analysis, is the only definite solution for differentiating heterozygote carriers from affected asymptomatic patients. Routine genetic testing, because of the multitude of documented mutations, has been thought to be impractical until recently. However, genetic testing is now being more actively applied to the diagnosis of WD, particularly in young children in whom conventional biochemical diagnosis has much limitation and only genetic testing is able to confirm WD. Because advancement of modern biochemical technology now allows more rapid, easier, and less expensive mutation detection, direct DNA sequencing could be actively considered as the primary mode of diagnostic investigation rather than a supplementary test to the conventional biochemical tests. This review will focus on the recent advancement of molecular genetics and genetic diagnosis of WD in very young children on the basis of research data of the Seoul National University Children's Hospital and recent literature. PMID:24010089

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

    PubMed Central

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

    2012-01-01

    The scope of conditions for which preimplantation genetic diagnosis (PGD) is licensed has recently been expanded in the United Kingdom to include genetic predisposition to adult-onset cancer. This qualitative interview study explores reproductive decision making, knowledge of and attitudes to reproductive genetic testing (prenatal diagnosis and PGD) with 25 women aged 18–45 years who received a positive BRCA test in the United Kingdom before having children. In this cohort of younger women, BRCA testing was motivated by risk management decisions; for some, BRCA status has affected their later decisions about having children. The perceived severity of hereditary breast/ovarian cancer (HBOC) influences thoughts about passing on the mutation to children and willingness to consider reproductive genetic testing, but most participants do not believe HBOC is a condition for which pregnancy termination is justified. PGD is considered more acceptable and advantageous because it would prevent transmission to future generations, but women have concerns about selecting embryos and the fact that they and affected family members would not have been selected. Women would also be deterred by the need to undergo in vitro fertilisation (IVF) and ovarian stimulation for PGD. Awareness of reproductive testing options was very variable among the cohort. The findings highlight the complexities of reproductive decision making for young women who knowingly carry a BRCA mutation, and the dilemmas inherent to reproductive genetic testing when the condition being tested for also affects a prospective parent. Counselling and psychological support for BRCA-positive women and couples concerning reproductive options are strongly indicated. PMID:21811309

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

    PubMed Central

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

    2015-01-01

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

  10. 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

  11. 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

  12. Genetic information in the diagnosis and treatment of hypertension

    Microsoft Academic Search

    Maciej Tomaszewski; Lukas Zimmerli; Fadi J. Charchar; Anna F. Dominiczak

    2006-01-01

    Advancement in cardiovascular science should be measured by a number of new diagnostic and therapeutic options applied in\\u000a clinical practice as a result of translational research. Hypertension genetics is a good example of such a successful transfer\\u000a of knowledge from bench to bedside. There are genetic methods currently used as diagnostic tools in patients presenting with\\u000a secondary forms of hypertension,

  13. Molecular genetics of bladder cancer: targets for diagnosis and therapy.

    PubMed

    Baffa, R; Letko, J; McClung, C; LeNoir, J; Vecchione, A; Gomella, L G

    2006-06-01

    Transitional cell carcinoma of the bladder is a common tumor. While most patients presenting superficial disease can be expected to do well following treatment, still many patients will return to our office with muscle invasive and metastatic disease. Survival in advanced bladder cancer is less than 50%. Tumors of similar histologic grade and stage have variable behavior, suggesting that genetic alterations must be present to explain the diverse behavior of bladder cancer. It is hoped that through the study of the subtle genetic alterations in bladder cancer, important prognostic and therapeutic targets can be exploited. Many new diagnostic tests and gene therapy approaches rely on the identification and targeting of these unique genetic alterations. A review of literature published on the molecular genetics of bladder cancer from 1970 to the present was conducted. A variety of molecular genetic alterations have been identified in bladder cancer. Oncogenes (H-ras, erbB-2, EGFR, MDM2, C-MYC, CCND1), tumor suppressor genes (p53, Rb, p21, p27/KIP1, p16, PTEN, STK15, FHIT, FEZ1/LZTS1, bc10), telomerase, and methylation have all been studied in bladder cancer. Several have proven to be potentially useful clinical targets in the prognosis and therapy of bladder cancer such as staining for p53 and gene therapy strategies such as p53 and fez1. Clinical trials targeting HER2/neu and the EGFR pathways are underway. The UroVysion bladder cancer assay relies on FISH to detect genetic alterations in this disease. Continuing identification of the molecular genetic alterations in bladder cancer will enhance future diagnostic and therapeutic approaches to bladder cancer. Capitalizing on these alterations will allow early detection, providing important prognostic information and unique targets for gene therapy and other therapeutic approaches. PMID:16918124

  14. Quality management system in PGD\\/PGS: now is the time

    Microsoft Academic Search

    Xavier Vendrell; Raquel Carrero; Trinitat Alberola; Rosa Bautista-Llácer; Elena García-Mengual; Reyes Claramunt; Manuel Pérez-Alonso

    2009-01-01

    Purpose  Governments and international authorities require an accreditation of the PGD\\/PGS laboratories in order to ensure the safety\\u000a and reproducibility of these analytical procedures. The implementation of a Quality Management System is the first mandatory\\u000a step prior to accreditation. Our aim is to offer a detailed guidance to the PGD\\/PGS community that would like to implement\\u000a this system in the future.

  15. An interaction between L-prostaglandin D synthase and arrestin increases PGD2 production.

    PubMed

    Mathurin, Karine; Gallant, Maxime A; Germain, Pascale; Allard-Chamard, Hugues; Brisson, Jessy; Iorio-Morin, Christian; de Brum Fernandes, Artur; Caron, Marc G; Laporte, Stéphane A; Parent, Jean-Luc

    2011-01-28

    L-type prostaglandin synthase (L-PGDS) produces PGD(2), a lipid mediator involved in neuromodulation and inflammation. Here, we show that L-PGDS and arrestin-3 (Arr3) interact directly and can be co-immunoprecipitated endogenously from MG-63 osteoblasts. Perinuclear L-PGDS/Arr3 co-localization is observed in PGD(2)-producing MG-63 cells and is induced by the addition of the L-PGDS substrate or co-expression of COX-2 in HEK293 cells. Inhibition of L-PGDS activity in MG-63 cells triggers redistribution of Arr3 and L-PGDS to the cytoplasm. Perinuclear localization of L-PGDS is detected in wild-type mouse embryonic fibroblasts (MEFs) but is more diffused in MEFs-arr-2(-/-)-arr-3(-/-). Arrestin-3 promotes PGD(2) production by L-PGDS in vitro. IL-1?-induced PGD(2) production is significantly lower in MEFs-arr-2(-/-)-arr-3(-/-) than in wild-type MEFs but can be rescued by expressing Arr2 or Arr3. A peptide corresponding to amino acids 86-100 of arrestin-3 derived from its L-PGDS binding domain stimulates L-PGDS-mediated PGD(2) production in vitro and in MG-63 cells. We report the first characterization of an interactor/modulator of a PGD(2) synthase and the identification of a new function for arrestin, which may open new opportunities for improving therapies for the treatment of inflammatory diseases. PMID:21112970

  16. Aligning policy to promote cascade genetic screening for prevention and early diagnosis of heritable diseases.

    PubMed

    George, Rani; Kovak, Karen; Cox, Summer L

    2015-06-01

    Cascade genetic screening is a methodology for identifying and testing close blood relatives of individuals at increased risk for heritable conditions and follows a sequential process, minimizing testing costs and the number of family members who need to be tested. It offers considerable potential for cost savings and increased awareness of heritable conditions within families. CDC-classified Tier 1 genomic applications for hereditary breast and ovarian cancer syndrome (HBOC), Lynch Syndrome (LS), and familial hypercholesterolemia (FH) are recommended for clinical use and support the use of cascade genetic screening. Most individuals are unaware of their increased risk for heritable conditions such as HBOC, LS, and FH. Consistent implementation of cascade genetic screening could significantly increase awareness and prevention of heritable conditions. Limitations to effective implementation of cascade genetic screening include: insufficient genetic risk assessment and knowledge by a majority of healthcare providers without genetics credentials; a shortage of genetic specialists, especially in rural areas; a low rate of reimbursement for comprehensive genetic counseling services; and an individual focus on prevention by clinical guidelines and insurance coverage. The family-centric approach of cascade genetic screening improves prevention and early diagnosis of heritable diseases on a population health level. Cascade genetic screening could be better supported and augmented through changes in health policy. PMID:25577298

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  18. A genetic algorithm for pancreatic cancer diagnosis Charalampos Moschopoulos1,2

    E-print Network

    A genetic algorithm for pancreatic cancer diagnosis Charalampos Moschopoulos1,2 , Dusan Popovic1.DeMoor, Yves.Moreau}@esat.kuleuven.be, gbeligia@uwg.gr Abstract. Pancreatic cancer is one of the leading causes various cancer types. In this study we aim to facilitate early detection of the pancreatic cancer

  19. Effect of Genetic Cancer Risk Assessment on Surgical Decisions at Breast Cancer Diagnosis

    Microsoft Academic Search

    Jeffrey N. Weitzel; Sarah M. McCaffrey; Raluca Nedelcu; Deborah J. MacDonald; Kathleen R. Blazer; Carey A. Cullinane

    2003-01-01

    Hypothesis: Breast cancer gene (BRCA) mutation sta- tus affects patients' surgical decisions when genetic can- cer risk assessment is offered at the time of breast can- cer diagnosis, prior to definitive treatment. Patients and Interventions: Outcomes following ge- netic cancer risk assessment were studied for women newly diagnosed as having breast cancer who were pro- spectively enrolled in an institutional

  20. 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.

  1. Application of Genetic Algorithms and Possibility Theory in Rolling Bearing Compound Fault Diagnosis

    Microsoft Academic Search

    Luo Zhi-gao; Pang Chao-li; Chen Bao-lei; Chen Peng

    2010-01-01

    The characteristic parameters of mechanical fault are found, on the basis of characteristic component collection according to wavelet transform, through optimizing the commonly-used characteristic parameters reflecting rolling bearing fault by genetic algorithms theory. The relationship between the characteristic fault and the mode of fault is created based on the possibility theory. The article also studies the successive fault diagnosis method

  2. Diagnosis, genetics, and management of inherited bone marrow failure syndromes.

    PubMed

    Alter, Blanche P

    2007-01-01

    The inherited bone marrow failure syndromes are traditionally considered to be pediatric disorders, but in fact, many of the patients now are diagnosed as adults, and many diagnosed as children now live to reach adulthood. The most common of these rare disorders include Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome and amegakaryocytic thrombocytopenia, which often develop aplastic anemia and may evolve into myelodysplastic syndrome and acute myeloid leukemia; and Diamond-Blackfan anemia, severe congenital neutropenia, and thrombocytopenia absent radii, single cytopenias that rarely if ever become aplastic but have increased risks of leukemia. In addition, the first three syndromes have high risks of solid tumors: head and neck and anogenital squamous cell carcinoma in Fanconi anemia and dyskeratosis congenita, and osteogenic sarcoma in Diamond-Blackfan anemia. Diagnosis of a marrow failure syndrome requires recognition of characteristic physical abnormalities when present, and consideration of these disorders in the differential diagnosis of patients who present with "acquired" aplastic anemia, myelodysplastic syndrome, acute myeloid leukemia, or atypically early cancers of the types seen in the syndromes. Ultimate proof will come from identification of pathogenic mutations in genes associated with each syndrome. PMID:18024606

  3. Molecular diagnosis of inheritable neuromuscular disorders. Part II: Application of genetic testing in neuromuscular disease.

    PubMed

    Greenberg, Steven A; Walsh, Ronan J

    2005-04-01

    Molecular genetic advances have led to refinements in the classification of inherited neuromuscular disease, and to methods of molecular testing useful for diagnosis and management of selected patients. Testing should be performed as targeted studies, sometimes sequentially, but not as wasteful panels of multiple genetic tests performed simultaneously. Accurate diagnosis through molecular testing is available for the vast majority of patients with inherited neuropathies, resulting from mutations in three genes (PMP22, MPZ, and GJB1); the most common types of muscular dystrophies (Duchenne and Becker, facioscapulohumeral, and myotonic dystrophies); the inherited motor neuron disorders (spinal muscular atrophy, Kennedy's disease, and SOD1 related amyotrophic lateral sclerosis); and many other neuromuscular disorders. The role of potential multiple genetic influences on the development of acquired neuromuscular diseases is an increasingly active area of research. PMID:15704143

  4. 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.

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

    PubMed

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

    2015-10-01

    Prostaglandins (PGs) play a key role in the development on the immune response through the regulation of both pro- and anti-inflammatory processes. PGD2 can be either pro- or anti-inflammatory depending on the inflammatory milieu. Prostaglandin D synthase (PGDS) is the enzyme responsible for the conversion of PGH2 to PGD2. In mammals, two types of PGDS synthase have been described, the hematopoietic (H-PGDS) and the lipocalin (L-PGDS). In the present study we describe the existence of two orthologs of the mammalian L-PGDS (PGDS1 and PGDS2) in the gilthead seabream and characterize their gene expression profiles and biological activity. The results showed a dramatic induction of the gene coding for PGDS1 in acidophilic granulocytes (AGs), which are functionally equivalent to mammalian neutrophils, after a prolonged in vitro activation with different pathogen associated molecular patterns (PAMPs). In contrast PGDS2 was not expressed in these cells. The functional relevance of the induction of PGDS1 in AGs was confirmed by the ability of these cells to release PGD2 upon PAMP stimulation. To gain further insight into the role of PGD2 in the resolution of inflammation in fish, we examined the ability of PGD2 or its cyclopentenone derivates (cyPGs) to modulate the main functional activities of AGs. It was found that both PGD2 and cyPGs inhibited the production of reactive oxygen species and downregulated the transcript levels of the gene encoding interleukin-1?. Taken together, these results demonstrate that the use of PGD2 and its metabolites in the resolution of inflammation was established before the divergence of fish from tetrapods more than 450 million years ago and support a critical role for granulocytes in the resolution of inflammation in vertebrates. PMID:26027798

  6. 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

  7. Citrullinemia type 1: genetic diagnosis and prenatal diagnosis in subsequent pregnancy.

    PubMed

    Karthikeyan, G; Jagadeesh, Sujatha; Seshadri, Suresh; Häberle, J

    2013-10-01

    Citrullinemia type 1 was diagnosed by tandem mass spectrometry in a full term male neonate who presented with an acute catastrophic collapse on the 3rd day of life. Both parents were identified to be carriers for the exon 15 p Gly390Arg mutation in the argininosuccinate synthetase gene located at chromosome 9q34.1. Chorionic villus sampling and prenatal genetic testing in the subsequent pregnancy revealed an affected fetus resulting in termination of pregnancy. PMID:24222285

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

    PubMed

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

    2015-04-01

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

  9. Rapid Whole-Genome Sequencing for Genetic Disease Diagnosis in Neonatal Intensive Care Units

    PubMed Central

    Saunders, Carol Jean; Miller, Neil Andrew; Soden, Sarah Elizabeth; Dinwiddie, Darrell Lee; Noll, Aaron; Alnadi, Noor Abu; Andraws, Nevene; Patterson, Melanie LeAnn; Krivohlavek, Lisa Ann; Fellis, Joel; Humphray, Sean; Saffrey, Peter; Kingsbury, Zoya; Weir, Jacqueline Claire; Betley, Jason; Grocock, Russell James; Margulies, Elliott Harrison; Farrow, Emily Gwendolyn; Artman, Michael; Safina, Nicole Pauline; Petrikin, Joshua Erin; Hall, Kevin Peter; Kingsmore, Stephen Francis

    2014-01-01

    Monogenic diseases are frequent causes of neonatal morbidity and mortality, and disease presentations are often undifferentiated at birth. More than 3500 monogenic diseases have been characterized, but clinical testing is available for only some of them and many feature clinical and genetic heterogeneity. Hence, an immense unmet need exists for improved molecular diagnosis in infants. Because disease progression is extremely rapid, albeit heterogeneous, in newborns, molecular diagnoses must occur quickly to be relevant for clinical decision-making. We describe 50-hour differential diagnosis of genetic disorders by whole-genome sequencing (WGS) that features automated bioinformatic analysis and is intended to be a prototype for use in neonatal intensive care units. Retrospective 50-hour WGS identified known molecular diagnoses in two children. Prospective WGS disclosed potential molecular diagnosis of a severe GJB2-related skin disease in one neonate; BRAT1-related lethal neonatal rigidity and multifocal seizure syndrome in another infant; identified BCL9L as a novel, recessive visceral heterotaxy gene (HTX6) in a pedigree; and ruled out known candidate genes in one infant. Sequencing of parents or affected siblings expedited the identification of disease genes in prospective cases. Thus, rapid WGS can potentially broaden and foreshorten differential diagnosis, resulting in fewer empirical treatments and faster progression to genetic and prognostic counseling. PMID:23035047

  10. 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, the degree to which these genetic variants improve breast cancer diagnosis in concert with mammography of the genetic variants significantly improved breast cancer diagnosis based on mammographic findings

  11. 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

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

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    2013-11-01

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

  14. 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

  15. 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

  16. [Noninvasive prenatal genetic diagnosis: a bioethical reflection on the use of noninvasive prenatal diagnosis from the analysis of nucleic acids present in maternal peripheral blood].

    PubMed

    González-Melado, Fermín J; Di Pietro, Maria Luisa

    2011-01-01

    The use of techniques that analyse the fetal nucleic acids present in maternal peripheral blood for the preparation of non-invasive prenatal genetic diagnosis, is a clinical reality in the case of certain diseases. In the coming years, it will become part of the routine monitoring for fetal diagnosis. This study analyzes the current status of these techniques as well as the major ethical issues arising from the relationship between - prenatal diagnosis and eugenic abortion, and the specific problems posed by - prenatal genetic diagnosis based an analysis of the nucleic acids present in maternal peripheral blood. Among the conclusions are the following: we make a positive ethical evaluation of the technique when it is aimed at pregnant women who are in a situation of high risk, defined on the basis of medical standards and ethics, without compromising the integrity of the fetus. We make a negative ethical evaluation when non-invasive prenatal genetic diagnosis has a eugenic purpose and will establish a connection between prenatal diagnosis and eugenic abortion in case of a positive result. Non-invasive prenatal diagnosis increases the image of the disabled person as an individual that has to be excluded from society. The widespread use of non-invasive prenatal diagnosis will decrease the autonomy of women / couples when it comes to making decisions. Health authorities may use non-invasive prenatal diagnosis as a way of ?preventing? genetic diseases, since it will lower costs, increase the number of malformed fetuses detected and a decrease the number of indirect abortions involving invasive techniques. PMID:21692554

  17. [Markers for non-invasive molecular genetic diagnosis of oncourological diseases].

    PubMed

    Mikha?lenko, D S; Perepechin, D V; Apolikhin, O I; Efremov, G D; Sivkov, A V

    2014-01-01

    Currently, there is accumulated mass of data on the molecular-genetic disorders in prostate cancer (PCa), bladder cancer (BC) and renal cancer (RC). Tumor cells in these diseases are present in the urine sediment; their number is sufficient for molecular genetic analysis that makes possible the development of noninvasive diagnosis of oncourological diseases. A characteristic feature of PCa includes the overexpression of the PCA3 gene; assay kit Progensa™ to quantify such overexpression has been developed; approximately 50% of tumors express a TMPRSS2-ERG chimeric oncogene. Combined analysis of PCA3 and TMPRSS2-ERG allows to detect PCa with a diagnostic accuracy of 84%, which is significantly higher than that of prostate specific antigen test. As a potential markers of BC, there are somatic mutations in FGFR3, PIK3CA, TERT genes in urine sediment, which are found in this disease with a frequency of about 60, 30 and 50%, respectively. The basis of the test system for DNA diagnosis of BC in urine sediment may include a definition of a combination of mutations in these genes with microsatellite instability. Aberrant methylation of the 5'-regulatory regions of tumor suppressor genes, integrated in the panel, also is considered as a tool in the diagnosis of RC (VHL, RASSF1, RARB2, CDH1), PCa (GSTP1, PTGS2, LGALS3) and BC (RASSF1, APC, SFRP2) after standardization of panels of loci investigated, sample preparation methods, bisulfite conversion, and the design of primers and probes. Thus, a test systems for molecular genetic diagnosis of oncourological diseases in urine sediment are currently available or may be developed in the near future. PMID:25807773

  18. Combination of broad molecular screening and cytogenetic analysis for genetic risk assignment and diagnosis in patients with acute leukemia

    Microsoft Academic Search

    S Meyer-Monard; V Parlier; J Passweg; D Mühlematter; U Hess; M Bargetzi; T Kühne; C Cabrol; A Gratwohl; M Jotterand; A Tichelli

    2006-01-01

    We evaluated the impact of genetic analysis combining cytogenetics and broad molecular screening on leukemia diagnosis according to World Health Organization (WHO) and on genetic risk assignment. A two-step nested multiplex RT–PCR assay was used that allowed the detection of 29 fusion transcripts. A total of 186 patients (104 males (56%), 174 adults (94%), 12 children (6%), 155 AML (83%),

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

    PubMed Central

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

    2013-01-01

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

  20. [Announcing the diagnosis of a genetic disease and psychological care of the patient and family].

    PubMed

    Lacombe, Didier; Toussaint, Eva

    2007-03-01

    Announcing a diagnostic of genetic disease to a child is for parents such a pain, also brutal and destructive. Even if the physician chooses the best moment, the right words, it's a sign of a rupture, a real disaster combined with physical feeling of bascule and temporo-spacial confusion. It's a beach in their flesh, a lost of identity, a profound norcissic failure. In addition this feature is associated with a high feeling of guilt failure with sometimes non logical imaginary structures. All those testimonies confirm that the identification of a genetic disease is a key in the family history. Announcing a diagnostic almost stay in mind as a bad new enduring a period of life when disease was absent or undiagnosed. Even if previews complementary investigations were done, the revelation still stays a mess. Also the diagnosis could be a relief the beginning of a new life with possibility of rebuilding. Regarding genetic diseases, it's the whole family that is concerned. The patients will deal with the diseases daily sometimes invisible by the circle. After the announcement of the diagnosis, the parents will have to structure that life according to the changes that the diseases rags in the family Brothers and sisters will have to find their place compared to this affetted brother or sister. In the some time as finding answers too many questions. The grand parents may feel guilty and wonder how to help the parents. The main part to this psychological approach in genetic diseases is to give each member of the family his role. PMID:17546763

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

    PubMed Central

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

    2014-01-01

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

  2. Do parental perceptions and motivations towards genetic testing and prenatal diagnosis for deafness vary in different cultures?

    PubMed

    Nahar, Risha; Puri, Ratna D; Saxena, Renu; Verma, Ishwar C

    2013-01-01

    Surveys of attitudes of individuals with deafness and their families towards genetic testing or prenatal diagnosis have mostly been carried out in the West. It is expected that the perceptions and attitudes would vary amongst persons of different cultures and economic background. There is little information on the prevailing attitudes for genetic testing and prenatal diagnosis for deafness in developing countries. Therefore, this study evaluates the motivations of Indian people with inherited hearing loss towards such testing. Twenty-eight families with history of congenital hearing loss (23 hearing parents with child/family member with deafness, 4 couples with both partners having deafness and 1 parent and child with deafness) participated in a semi-structured survey investigating their interest, attitudes, and intentions for using genetic and prenatal testing for deafness. Participants opinioned that proper management and care of individuals with deafness were handicapped by limited rehabilitation facilities with significant financial and social burden. Nineteen (68%) opted for genetic testing. Twenty-six (93%) expressed high interest in prenatal diagnosis, while 19 (73%) would consider termination of an affected fetus. Three hearing couples, in whom the causative mutations were identified, opted for prenatal diagnosis. On testing, all the three fetuses were affected and the hearing parents elected to terminate the pregnancies. This study provides an insight into the contrasting perceptions towards hearing disability in India and its influence on the desirability of genetic testing and prenatal diagnosis. PMID:23208825

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

    PubMed

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Zhang, Yongxiang; Randall, R. B.

    2009-07-01

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

  5. 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

  6. 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

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

    PubMed

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

    2012-09-01

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

  8. Beware! Preimplantation genetic diagnosis may solve some old problems but it also raises new ones.

    PubMed Central

    Draper, H; Chadwick, R

    1999-01-01

    Preimplantation genetic diagnosis (PIGD) goes some way to meeting the clinical, psychological and ethical problems of antenatal testing. We should guard, however, against the assumption that PIGD is the answer to all our problems. It also presents some new problems and leaves some old problems untouched. This paper will provide an overview of how PIGD meets some of the old problems but will concentrate on two new challenges for ethics (and, indeed, law). First we look at whether we should always suppose that it is wrong for a clinician to implant a genetically abnormal zygote. The second concern is particularly important in the UK. The Human Fertilisation and Embryology Act (1990) gives clinicians a statutory obligation to consider the interests of the future children they help to create using in vitro fertilisation (IVF) techniques. Does this mean that because PIGD is based on IVF techniques the balance of power for determining the best interests of the future child shifts from the mother to the clinician? PMID:10226915

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

    PubMed Central

    2011-01-01

    Background The prostaglandin D2 (PGD2) pathway is involved in numerous biological processes and while it has been identified as a partner of the embryonic sex determining male cascade, the roles it plays in ovarian function remain largely unknown. PGD2 is secreted by two prostaglandin D synthases (Pgds); the male-specific lipocalin (L)-Pgds and the hematopoietic (H)-Pgds. Methods To study the expression of the Pgds in the adult ovary, in situ hybridization were performed. Then, to evaluate the role of H-Pgds produced PGD2 in the ovarian physiology, adult female mice were treated with HQL-79, a specific inhibitor of H-Pgds enzymatic activity. The effects on expression of the gonadotrophin receptors FshR and LhR, steroidogenic genes Cyp11A1, StAR and on circulating progesterone and estradiol, were observed. Results We report the localization of H-Pgds mRNA in the granulosa cells from the primary to pre-ovulatory follicles. We provide evidence of the role of H-Pgds-produced PGD2 signaling in the FSH signaling through increased FshR and LhR receptor expression. This leads to the activation of steroidogenic Cyp11A1 and StAR gene expression leading to progesterone secretion, independently on other prostanoid-synthetizing mechanisms. We also identify a role whereby H-Pgds-produced PGD2 is involved in the regulation of follicular growth through inhibition of granulosa cell proliferation in the growing follicles. Conclusions Together, these results show PGD2 signaling to interfere with FSH action within granulosa cells, thus identifying an important and unappreciated role for PGD2 signaling in modulating the balance of proliferation, differentiation and steroidogenic activity of granulosa cells. PMID:21352547

  10. 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

  11. Targeted next-generation sequencing for the genetic diagnosis of dysferlinopathy.

    PubMed

    Shin, Ha Young; Jang, Hoon; Han, Joo Hyung; Park, Hyung Jun; Lee, Jung Hwan; Kim, So Won; Kim, Seung Min; Park, Young-Eun; Kim, Dae-Seong; Bang, Duhee; Lee, Min Goo; Lee, Ji Hyun; Choi, Young-Chul

    2015-06-01

    Dysferlinopathy comprises a group of autosomal recessive muscular dystrophies caused by mutations in the DYSF gene. Due to the large size of the gene and its lack of mutational hot spots, analysis of the DYSF gene is time-consuming and laborious using conventional sequencing methods. By next-generation sequencing (NGS), DYSF gene analysis has previously been validated through its incorporation in multi-gene panels or exome analyses. However, individual validation of NGS approaches for DYSF gene has not been performed. Here, we established and validated a hybridization capture-based target-enrichment followed by next-generation sequencing to detect mutations in patients with dysferlinopathy. With this approach, mean depth of coverage was approximately 450 fold and almost all (99.3%) of the targeted region had sequence coverage greater than 20 fold. When this approach was tested on samples from patients with known DYSF mutations, all known mutations were correctly retrieved. Using this method on 32 consecutive patient samples with dysferlinopathy, at least two pathogenic variants were detected in 28 (87.5%) samples and at least one pathogenic variant was identified in all samples. Our results suggested that the NGS-based screening method could facilitate efficient and accurate genetic diagnosis of dysferlinopathy. PMID:25868377

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

    PubMed Central

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

    2015-01-01

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

  13. 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

  14. Impact of a Genetic Diagnosis of a Mitochondrial Disorder 5–17 Years After the Death of an Affected Child

    Microsoft Academic Search

    A. C. Sexton; M. Sahhar; D. R. Thorburn; S. A. Metcalfe

    2008-01-01

    This study used in-depth interviews to explore the experiences of parents who were re-contacted with new genetic results many\\u000a years after the death of a child with a mitochondrial disorder. At the time of their child’s illness, parents had consented\\u000a to a tissue sample being taken to help with diagnosis of a suspected mitochondrial disorder, and subsequently further DNA\\u000a testing

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

    PubMed

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

    2014-08-01

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

  16. SUPPLEMENTARY FIGURES LEGEND Supplementary Figure 1. Growth of the pgdA mutant in serum. Despite the in vitro

    E-print Network

    Boyer, Edmond

    in 25% fetal calf serum independently of prior decomplementation (A). Growth in 25% serum correlated1 SUPPLEMENTARY FIGURES LEGEND Supplementary Figure 1. Growth of the pgdA mutant in serum. Despite amounts of lysozyme found in the serum. Supplementary Figure 2. Morphology of L. monocytogenes EGDe (A

  17. PGD and aneuploidy screening for 24 chromosomes: advantages and disadvantages of competing platforms.

    PubMed

    Bisignano, A; Wells, D; Harton, G; Munné, S

    2011-12-01

    Diagnosis of embryos for chromosome abnormalities, i.e. aneuploidy screening, has been invigorated by the introduction of microarray-based testing methods allowing analysis of 24 chromosomes in one test. Recent data have been suggestive of increased implantation and pregnancy rates following microarray testing. Preimplantation genetic diagnosis for infertility aims to test for gross chromosome changes with the hope that identification and transfer of normal embryos will improve IVF outcomes. Testing by some methods, specifically single-nucleotide polymorphism (SNP) microarrays, allow for more information and potential insight into parental origin of aneuploidy and uniparental disomy. The usefulness and validity of reporting this information is flawed. Numerous papers have shown that the majority of meiotic errors occur in the egg, while mitotic errors in the embryo affect parental chromosomes at random. Potential mistakes made in assigning an error as meiotic or mitotic may lead to erroneous reporting of results with medical consequences. This study's data suggest that the bioinformatic cleaning used to 'fix' the miscalls that plague single-cell whole-genome amplification provides little improvement in the quality of useful data. Based on the information available, SNP-based aneuploidy screening suffers from a number of serious issues that must be resolved. PMID:21856229

  18. 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

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

    PubMed Central

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

    2014-01-01

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

  20. 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.

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

    PubMed Central

    2012-01-01

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

  2. 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

  3. [Prenatal genetic diagnosis of type I autosomal dominant polycystic kidney disease].

    PubMed

    Klaus, Z; Kozáry, M; Czeizel, E

    1997-06-15

    Probanda affected with autosomal dominant polycystic kidney disease (ADPKD) had a molecular genetic analysis which indicated the type I. Of the three pregnancies in the probanda, first two had mutant gene carrier fetuses and these pregnancies were terminated. The fetus of the third pregnancy had no mutant gene and this pregnancy ended in the birth of a healthy boy. The principles of genetic counselling and antenatal care are summarised in ADPKD type I. PMID:9254374

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

    Microsoft Academic Search

    Meral Özgüç

    2011-01-01

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

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

    Microsoft Academic Search

    Yongxiang Zhang; R. B. Randall

    2009-01-01

    The rolling element bearing is a key part in many mechanical facilities and the diagnosis of its faults is very important in the field of predictive maintenance. Till date, the resonant demodulation technique (envelope analysis) has been widely exploited in practice. However, much practical diagnostic equipment for carrying out the analysis gives little flexibility to change the analysis parameters for

  6. Rapid Genetic Diagnosis With the Transcription—Reverse Transcription Concerted Reaction System for Cancer Micrometastasis

    Microsoft Academic Search

    Takaaki Ishii; Yoshiyuki Fujiwara; Satoru Ohnaka; Toshinori Hayashi; Hirokazu Taniguchi; Shuji Takiguchi; Takushi Yasuda; Masahiko Yano; Morito Monden

    2004-01-01

    Background: Detection of cancer micrometastases is required for improvement of cancer therapy. The aim of this study was to establish a rapid and practical genetic assay to detect micrometastasis in gastric cancer and to assess its clinical significance with respect to prognosis. Methods: A novel RNA amplification system with transcription–reverse transcription concerted reaction (TRC) was introduced for quantitative detection of

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

    PubMed

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

    2013-10-15

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

  8. [The role of molecular genetics in diagnosis of hereditary motor-sensory neuropathy].

    PubMed

    Kocha?ski, A; Jedrzejowska, H; Ryniewicz, B; Budny, B

    2000-01-01

    Hereditary motor-sensory neuropathies (HMSN) are a heterogeneous group of disorders of peripheral nervous system. Four genes in HMSN have been characterized so far i.e.: PMP22, MPZ, Cx32 and EGR-2. The advent of molecular genetic techniques over the past few years has provided identification of molecular defects in a few forms of HMSN. The present study describes the application of modern molecular genetic methods, which are used in the studies of HMSN. Southern blot hybridisation, Fluorescence in situ hybridisation (FISH), Short Tandem Repeat analysis (STR), Semiquantitative PCR analysis (SQ-PCR), Single Strand Conformation Polymorphism method (SSCP), Heteroduplex analysis (HD) and finally DNA automated sequencing are described in the present paper. In the conclusions the advantages and limits of mentioned methods of DNA analysis in HMSN have been described. PMID:11253483

  9. Splicing mutation associated with Rett syndrome and an experimental approach for genetic diagnosis

    Microsoft Academic Search

    Liron Abuhatzira; Kirill Makedonski; Yael Petel Galil; Eva Gak; Bruria Ben Zeev; Aharon Razin; Ruth Shemer

    2005-01-01

    Around 80% of Rett syndrome (RS) cases have a mutation or deletion within the coding sequence of the MeCP2 gene. The other RS patients remain genetically undiagnosed. A significant fraction (10–15%) of disease-causing mutations in humans, affect pre-mRNA splicing. Two potential splice mutations were found in the MeCP2 gene in RS patients, however it was not clear whether these mutations

  10. Genetic testing improves the diagnosis of adult type hypolactasia in the Mediterranean population of Sardinia

    Microsoft Academic Search

    E Schirru; V Corona; P Usai-Satta; M Scarpa; F Oppia; F Loriga; F Cucca; S De Virgiliis; R Rossino; M Doloretta Macis; R-D Jores; M Congia

    2007-01-01

    Objective:Recently, the C\\/T-13910 polymorphism on chromosome 2q21 in North-European populations has been found completely associated with lactase activity and its genetic typing proposed as first-stage screening test for adult hypolactasia. However, the C\\/T-13910 variant in some sub-Saharan African groups is not a predictor of lactase persistence. In this work, we wanted to verify if in the Mediterranean island of Sardinia,

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

    PubMed

    Broschk, C; Distl, O

    2005-10-01

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

  12. Genetic programming for knowledge discovery in chest pain diagnosis Celia C. Bojarczuk 1 , Heitor S. Lopes 2 , Alex A. Freitas 3

    E-print Network

    Fernandez, Thomas

    Genetic programming for knowledge discovery in chest pain diagnosis Celia C. Bojarczuk 1 , Heitor S of discriminating among 12 different pathologies, whose main symptom is chest pain. In order to discover these rules predicting attributes and 12 different diseases (classes) whose main characteristic is the chest pain

  13. Ethical dilemmas in genetic testing: examples from the Cuban program for predictive diagnosis of hereditary ataxias.

    PubMed

    Mariño, Tania Cruz; Armiñán, Rubén Reynaldo; Cedeño, Humberto Jorge; Mesa, José Miguel Laffita; Zaldivar, Yanetza González; Rodríguez, Raúl Aguilera; Santos, Miguel Velázquez; Mederos, Luis Enrique Almaguer; Herrera, Milena Paneque; Pérez, Luis Velázquez

    2011-06-01

    Predictive testing protocols are intended to help patients affected with hereditary conditions understand their condition and make informed reproductive choices. However, predictive protocols may expose clinicians and patients to ethical dilemmas that interfere with genetic counseling and the decision making process. This paper describes ethical dilemmas in a series of five cases involving predictive testing for hereditary ataxias in Cuba. The examples herein present evidence of the deeply controversial situations faced by both individuals at risk and professionals in charge of these predictive studies, suggesting a need for expanded guidelines to address such complexities. PMID:21264501

  14. Dexamethasone Protects Neonatal Hypoxic-Ischemic Brain Injury via L-PGDS-Dependent PGD2-DP1-pERK Signaling Pathway

    PubMed Central

    Gonzalez-Rodriguez, Pablo J.; Li, Yong; Martinez, Fabian; Zhang, Lubo

    2014-01-01

    Background and Purpose Glucocorticoids pretreatment confers protection against neonatal hypoxic-ischemic (HI) brain injury. However, the molecular mechanism remains poorly elucidated. We tested the hypothesis that glucocorticoids protect against HI brain injury in neonatal rat by stimulation of lipocalin-type prostaglandin D synthase (L-PGDS)-induced prostaglandin D2 (PGD2)-DP1-pERK mediated signaling pathway. Methods Dexamethasone and inhibitors were administered via intracerebroventricular (i.c.v) injections into 10-day-old rat brains. Levels of L-PGD2, D prostanoid (DP1) receptor, pERK1/2 and PGD2 were determined by Western immunoblotting and ELISA, respectively. Brain injury was evaluated 48 hours after conduction of HI in 10-day-old rat pups. Results Dexamethasone pretreatment significantly upregulated L-PGDS expression and the biosynthesis of PGD2. Dexamethasone also selectively increased isoform pERK-44 level in the neonatal rat brains. Inhibitors of L-PGDS (SeCl4), DP1 (MK-0524) and MAPK (PD98059) abrogated dexamethasone-induced increases in pERK-44 level, respectively. Of importance, these inhibitors also blocked dexamethasone-mediated neuroprotective effects against HI brain injury in neonatal rat brains. Conclusion Interaction of glucocorticoids-GR signaling and L-PGDS-PGD2-DP1-pERK mediated pathway underlies the neuroprotective effects of dexamethasone pretreatment in neonatal HI brain injury. PMID:25474649

  15. [Medico-genetic study of isolates in Uzbekistan. IV. Clinico-biochemical diagnosis of hereditary diseases].

    PubMed

    Kozlova, S I; Diachenko, S S; Khannanova, F K; Kuleshov, N P; Khodzhaeva, G K

    1976-01-01

    An exhaustive clinico-biochemical examination of the population of two kishlaks of the Samarkand Region, viz. Karakent (210 persons) and Ishan (248 persons) was carried out. The program of this examination permitted to exclude over 160 forms of hereditary pathology. A total of 45 persons affected with diseases belonging to 12 nosological forms were revealed in the course of the examination. Among the diseases observed only 5 are hereditary sensu stricto, viz. myoclonus-epilepsy, Bonevi-Ulrich's syndrome, imperfect osteogenesis, pigment choreoretinite and Down's syndrome, others belong to diseases with a pronounced hereditary predisposition. The main part of this group comprises neuro-psychic diseases, such as non-differentiated olygophreny (5.0%), epilepsy (1.3%), schizophreny; many of these cases have a familial character, particularly in Karakent. Besides the persons suffering from diseases, 20 heterozygous carriers of beta-thalassemia and 17 heterozygous carriers of G6PD-deficiency were discovered in the kishlaks examined. On the whole the frequency of the diseases revealed did not exceed the level in the general population. Despite the different degree of isolation of the kishlaks examined (Karakent is isolated on a religious basis, F = 0.0064; while Ishan is a desintagrated isolate, F = = 0.0014), no substantial differences between them in the distribution of pathological phenomena were observed. On the basis of the experience of this expedition recomendations are proposed concerning the origination and accomplishment of medico-genetic expeditions. A scheme is proposed for the performance of medico-genetic examination through several stages. The first stage in the composition of tentative maps of the distribution of hereditary diseases within a region on the basis of the information obtained from the medical personnel and from the examination of the documents of district and regional hospitals. Subsequently the primary information is specified, the regions to be examined are determined, as well as concrete tasks and the staff of the expedition. The conclusive stage is the medico-genetic examination proper, including clinical, biochemical, immunological and cytogenetic diagnoses of hereditary pathological phenomena. The place of the disposition is a village or a district hospital. More complicated laboratory studies should be performed on the basis of the institution by which the expedition is formed. The results obtained by such expeditions would be important for the investigation of the problems of genogeography, for the discovery of new forms of mutant alleles, for the investigation of the causes and the conditions of the formation of the definite populational structure, of clinical polymorphism of human hereditary diseases. PMID:135712

  16. 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.

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

    PubMed Central

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

    2014-01-01

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

  18. Advances in pediatric restless legs syndrome: Iron, genetics, diagnosis and treatment.

    PubMed

    Picchietti, Matthew A; Picchietti, Daniel L

    2010-08-01

    A substantial literature characterizes pediatric restless legs syndrome (RLS), which occurs in about 1.9% of individuals between 8 and 18years of age. Diagnostic interview techniques and an updated inventory of pediatric RLS mimics are presented. Evidence for comorbidity of pediatric RLS with attention-deficit/hyperactivity disorder, depression, and anxiety is reviewed as is the relationship to periodic limb movements in sleep and periodic limb movement disorder. The role of relative iron deficiency in pediatric RLS is discussed, along with new data indicating the benefit of iron therapy in reducing symptoms. Five genetic variants have been linked to RLS, an important finding in a condition that is highly familial in early-onset cases. Numerous case reports and case series indicate benefit for moderate to severe pediatric RLS with medication. However, to date, there have been no double-blind, placebo-controlled studies of therapy for pediatric RLS published. These and other recent advances relevant to pediatric RLS research are reviewed. PMID:20620105

  19. Differential diagnosis and genetic analysis of the antigenically related swine vesicular disease virus and coxsackie viruses.

    PubMed

    Marquardt, O; Ohlinger, V F

    1995-06-01

    Monoclonal antibodies directed against an isolate of swine vesicular disease virus (SVDV), characterized by virus neutralization tests and competition assays, were used to compare SVDV isolates and isolates of the antigenically related Coxsackie viruses by ELISA. SVDV-specific reaction patterns and one specific for Coxsackie viruses were observed. This provided a method for distinguishing between these enteroviruses. In addition, RT-PCRs were undertaken with Coxsackie virus and SVDV genomes. Different product patterns were obtained which correlated with the genetic differences revealed by nucleotide sequence determination. RT-PCR distinguished between SVDV and Coxsackie viruses by pattern differences. Further SVDV-specific PCRs were carried out with clinical samples. Viral genomes were detected with a sensitivity equivalent to that of virus isolation in cell culture. Sequencing of the Coxsackie virus-derived 2A-coding PCR products resulted in a not previously described sequence of a B5 isolate and in SVDV-specific sequence of two Coxsackie virus A16 isolates. The differences of the isolates by ELISA and PCR reactivity, as well as the nucleotide sequence differences are consistent with the quasispecies concept of RNA viruses. PMID:7673387

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

    PubMed

    Jensen, Henrik Kjoerulf

    2002-11-01

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

  1. Genetics

    MedlinePLUS

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

  2. Genetic diagnosis of familial hypercholesterolaemia: the importance of functional analysis of potential splice-site mutations.

    PubMed

    Bourbon, M; Duarte, M A; Alves, A C; Medeiros, A M; Marques, L; Soutar, A K

    2009-05-01

    Familial hypercholesterolemia (FH) results from defective low-density lipoprotein receptor (LDLR) activity, mainly due to LDLR gene defects. Of the many different LDLR mutations found in patients with FH, about 6% of single base substitutions are located near or within introns, and are predicted to result in exon skipping, retention of an intron, or activation of cryptic sites during mRNA splicing. This paper reports on the Portuguese FH Study, which found 10 such mutations, 6 of them novel. For the mutations that have not been described before or those whose effect on function have not been analysed, their effect on splicing was investigated, using reverse transcriptase PCR analysis of LDLR mRNA from freshly isolated blood mononuclear cells. Two of these variants (c.313+6 T-->C, c.2389G-->T (p.V776L)) caused exon skipping, and one caused retention of an intron (c.1359-5C-->G), whereas two others (c.2140+5 G-->A and c.1061-8T-->C) had no apparent effect. Any effect of c.1185G-->C (p.V374V) on splicing could not be determined because it was on an allele with a promoter mutation (-42C-->G) that was probably not transcribed. Variants in four patients lost to follow-up could not be tested experimentally, but they almost certainly affect splicing because they disrupt the invariant AG or GT in acceptor (c.818-2A-->G) or donor (c.1060+1G-->A, c.1845+1delG and c.2547+1G-->A) spice sites. These findings emphasise that care must be taken before reporting the presence or absence of a splice-site mutation in the LDLR gene for diagnostic purposes. The study also shows that relatively simple, quick and inexpensive RNA assays can evaluate putative splicing mutations that are not always predictable by available software, thereby reducing genetic misdiagnosis of patients with FH. PMID:19411563

  3. Repairing fractures between data using genetic programming-based feature extraction: A case study in cancer diagnosis

    E-print Network

    Granada, Universidad de

    benchmark problems together with a real-world problem on prostate cancer diagnosis show the good behavior in cancer diagnosis Jose G. Moreno-Torres a, , Xavier Llorà b , David E. Goldberg c , Rohit Bhargava d Fractures between data Biological data Cancer diagnosis Different laboratories a b s t r a c

  4. 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.

  5. Bulgarian Jews in Israel: Genetic Blood Markers

    Microsoft Academic Search

    Sarah Nevo; Hartwig Cleve; Shulamit Bar-Shani; Alma Joel; Meir Liron

    1989-01-01

    Two hundred and sixteen unrelated Bulgarian Jews were typed for the following genetic systems: ABO, MNS, Rh, Kell and Duffy of the blood groups; ADA, AK1, ACP1, ESD, GLO, PGD, PGM1 and PGM2 of the red-cell enzymes, and for the serum proteins HP, GC and PI. A comparison of observed gene frequencies with those of two other Sephardi Jewish groups,

  6. 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.

  7. Prenatal findings and the genetic diagnosis of fetal overgrowth disorders: Simpson-Golabi-Behmel syndrome, Sotos syndrome, and Beckwith-Wiedemann syndrome.

    PubMed

    Chen, Chih-Ping

    2012-06-01

    With the advent of prenatal sonography, fetal overgrowth can be easily detected. Prenatal-onset overgrowth can be secondary to normal variants of familial tall stature, familial rapid maturation, diabetic macrosomia, and congenital nesidioblastosis, or prenatal-onset overgrowth can be primary due to pathological overgrowth disorders. This article provides a comprehensive review of the prenatal findings and the genetic diagnosis of some of the pathological prenatal-onset overgrowth disorders, such as Simpson-Golabi-Behmel syndrome, Sotos syndrome, and Beckwith-Wiedemann syndrome. PMID:22795092

  8. Moving toward a predictive and personalized clinical approach in amyotrophic lateral sclerosis: novel developments and future directions in diagnosis, genetics, pathogenesis and therapies.

    PubMed

    Nefussy, Beatrice; Drory, Vivian E

    2010-06-01

    Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease that affects upper and lower motor neurons in the brain and spinal cord, with progressive weakness and atrophy of most muscles in the body and is almost always fatal within 3-5 years. A small proportion of cases are familial, and remarkable achievements have been made during the last years in understanding the genetics of the disease. In spite of this, the basic pathogenic mechanisms underlying the sporadic disease are still poorly understood. There is urgent need for better understanding of the pathogenic processes in order to be able to develop effective treatments. The present review will focus on recent knowledge gained in diagnosis, genetics, pathogenesis and therapies in ALS. Future development of diagnostic technologies integrating genetic, environmental and individual information will enable us to predict a population at risk for ALS. New treatments actually in development will help improve the medical management of ALS patients, taking into consideration individual traits, as genetic background, and pave a way for a more effective personalized diagnostic and treatment approach. PMID:23199068

  9. Le diagnostic préimplantatoire couplé au typage HLA : l'expérience parisienne

    Microsoft Academic Search

    J. Steffann; N. Frydman; P. Burlet; N. Gigarel; E. Feyereisen; V. Kerbrat; G. Tachdjian; A. Munnich; R. Frydman

    2005-01-01

    Preimplantation genetic diagnosis (PGD) consists in the genetic analysis of one or two cells. These cells (blastomeres) are sampled from embryos, obtained by in vitro fertilization, at the third day of development. Since 1998, the bioethical laws (1994) and their decrees restricted PGD practices in France, strictly to the avoidance of the birth of a child affected with a genetic

  10. 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.

  11. Genetic Variation in the Prostaglandin E2 Pathway Is Associated with Primary Graft Dysfunction

    PubMed Central

    Akimova, Tatiana; Kazi, Altaf; Shah, Rupal J.; Cantu, Edward; Feng, Rui; Levine, Matthew H.; Kawut, Steven M.; Meyer, Nuala J.; Lee, James C.; Hancock, Wayne W.; Aplenc, Richard; Ware, Lorraine B.; Palmer, Scott M.; Bhorade, Sangeeta; Lama, Vibha N.; Weinacker, Ann; Orens, Jonathan; Wille, Keith; Crespo, Maria; Lederer, David J.; Arcasoy, Selim; Demissie, Ejigayehu; Christie, Jason D.

    2014-01-01

    Rationale: Biologic pathways with significant genetic conservation across human populations have been implicated in the pathogenesis of primary graft dysfunction (PGD). The evaluation of the role of recipient genetic variation in PGD has thus far been limited to single, candidate gene analyses. Objectives: We sought to identify genetic variants in lung transplant recipients that are responsible for increased risk of PGD using a two-phase large-scale genotyping approach. Methods: Phase 1 was a large-scale candidate gene association study of the multicenter, prospective Lung Transplant Outcomes Group cohort. Phase 2 included functional evaluation of selected variants and a bioinformatics screening of variants identified in phase 1. Measurements and Main Results: After genetic data quality control, 680 lung transplant recipients were included in the analysis. In phase 1, a total of 17 variants were significantly associated with PGD, four of which were in the prostaglandin E2 family of genes. Among these were a coding variant in the gene encoding prostaglandin E2 synthase (PTGES2; P = 9.3 × 10?5) resulting in an arginine to histidine substitution at amino acid position 298, and three variants in a block containing the 5? promoter and first intron of the PTGER4 gene (encoding prostaglandin E2 receptor subtype 4; all P < 5 × 10?5). Functional evaluation in regulatory T cells identified that rs4434423A in the PTGER4 gene was associated with differential suppressive function of regulatory T cells. Conclusions: Further research aimed at replication and additional functional insight into the role played by genetic variation in prostaglandin E2 synthetic and signaling pathways in PGD is warranted. PMID:24467603

  12. 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.

  13. Population Structure of the Chenchu and Other South Indian Tribal Groups: Relationships between Genetic, Anthropometric, Dermatoglyphic, Geographic, and Linguistic Distances

    E-print Network

    Sirajuddin, S. M.; Duggirala, R.; Crawford, Michael H.

    1994-10-01

    We describe the genetic structure and interrelationships of nine south Indian tribal groups (seven from Andhra Pradesh and two from the adjoining states of Tamil Nadu and Kerala) using seven polymorphic loci (ABO, MN, RH, PGM, ACP, PGD, and LDH). R...

  14. 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.

  15. 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

  16. 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…

  17. Genetics of laminin ?2 chain (or merosin) deficient congenital muscular dystrophy: from identification of mutations to prenatal diagnosis

    Microsoft Academic Search

    Pascale Guicheney; Nicolas Vignier; Anne Helbling-Leclerc; Marja Nissinen; Xu Zhang; Corrinne Cruaud; Jean-Claude Lambert; Christian Richelme; Haluk Topaloglu; Luciano Merlini; Annie Barois; Ketty Schwartz; Fernando M. S. Tomé; Karl Tryggvason; Michel Fardeau

    1997-01-01

    Congenital muscular dystropies (CMD) are a clinically and genetically heterogeneous group of muscle disorders, with autosomal recessive inheritance. Absence of the laminin ?2 chain in the skeletal muscle of patients with classical CMD has permitted the identification of a subgroup, referred to as ‘merosin-deficient CMD or laminin ?2 chain deficient CMD’. We first identified a nonsense and a splice site

  18. 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

  19. 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…

  20. Developing a Knowledge-Based System Using Rough Set Theory and Genetic Algorithms for Substation Fault Diagnosis

    Microsoft Academic Search

    Ching Lai Hor; Peter Crossley; Simon Watson; Dean Millar

    Supervisory Control and Data Acquisition (SCADA) systems are fundamental tools for quick fault diagnosis and efficient restoration\\u000a of power systems. When multiple faults, or malfunctions of protection devices occur in the system, the SCADA system issues\\u000a many alarm signals rapidly and relays these to the control center. The original cause and location of the fault can be difficult\\u000a to determine

  1. Glucocorticoid protects rodent hearts from ischemia/reperfusion injury by activating lipocalin-type prostaglandin D synthase-derived PGD2 biosynthesis.

    PubMed

    Tokudome, Satori; Sano, Motoaki; Shinmura, Ken; Matsuhashi, Tomohiro; Morizane, Shintaro; Moriyama, Hidenori; Tamaki, Kayoko; Hayashida, Kentaro; Nakanishi, Hiroki; Yoshikawa, Noritada; Shimizu, Noriaki; Endo, Jin; Katayama, Takaharu; Murata, Mitsushige; Yuasa, Shinsuke; Kaneda, Ruri; Tomita, Kengo; Eguchi, Naomi; Urade, Yoshihiro; Asano, Koichiro; Utsunomiya, Yasunori; Suzuki, Takeshi; Taguchi, Ryo; Tanaka, Hirotoshi; Fukuda, Keiichi

    2009-06-01

    Lipocalin-type prostaglandin D synthase (L-PGDS), which was originally identified as an enzyme responsible for PGD2 biosynthesis in the brain, is highly expressed in the myocardium, including in cardiomyocytes. However, the factors that control expression of the gene encoding L-PGDS and the pathophysiologic role of L-PGDS in cardiomyocytes are poorly understood. In the present study, we demonstrate that glucocorticoids, which act as repressors of prostaglandin biosynthesis in most cell types, upregulated the expression of L-PGDS together with cytosolic calcium-dependent phospholipase A2 and COX2 via the glucocorticoid receptor (GR) in rat cardiomyocytes. Accordingly, PGD2 was the most prominently induced prostaglandin in vivo in mouse hearts and in vitro in cultured rat cardiomyocytes after exposure to GR-selective agonists. In isolated Langendorff-perfused mouse hearts, dexamethasone alleviated ischemia/reperfusion injury. This cardioprotective effect was completely abrogated by either pharmacologic inhibition of COX2 or disruption of the gene encoding L-PGDS. In in vivo ischemia/reperfusion experiments, dexamethasone reduced infarct size in wild-type mice. This cardioprotective effect of dexamethasone was markedly reduced in L-PGDS-deficient mice. In cultured rat cardiomyocytes, PGD2 protected against cell death induced by anoxia/reoxygenation via the D-type prostanoid receptor and the ERK1/2-mediated pathway. Taken together, these results suggest what we believe to be a novel interaction between glucocorticoid-GR signaling and the cardiomyocyte survival pathway mediated by the arachidonic acid cascade. PMID:19451694

  2. Single cell CGH analysis reveals a high degree of mosaicism in human embryos from patients with balanced structural chromosome aberrations

    Microsoft Academic Search

    H. Malmgren; S. Sahlen; J. Inzunza; M. Aho; B. Rosenlund; M. Fridstrom; O. Hovatta; L. Ahrlund-Richter; M. Nordenskjold; E. Blennow

    2002-01-01

    We have performed comparative genomic hybridization (CGH) analysis of single blastomeres from human preimplantation embryos of patients undergoing preimplantation genetic diagnosis (PGD) for inherited structural chromosome aberrations and from embryos of IVF couples without known chromosomal aberrations. The aim was to verify the PGD results for the specific translocation, reveal the overall genetic balance in each cell and visualize the

  3. Karyotypic and Molecular Genetic Changes Associated With Fetal Cardiovascular Abnormalities: Results of a Retrospective 4-Year Ultrasonic Diagnosis Study

    PubMed Central

    Bao, Bihui; Wang, Yu; Hu, Hua; Yao, Hong; Li, Yuyan; Tang, Shuai; Zheng, Lihong; Xu, Yan; Liang, Zhiqing

    2013-01-01

    Objective: To investigate the incidence of aneuploidy in fetuses with congenital heart defects (CHDs) and to further identify submicroscopic changes and global DNA methylation levels as potential biomarkers in complex CHD cases. Methods: Fetuses at high risk for birth defects or with obvious sonographic anomalies were recruited at the Prenatal Diagnosis Center and Ultrasonic Diagnosis Center. Elective fetal karyotyping and DNA copy number and promoter methylation analyses were carried out following parental consent. G-banded karyotyping was performed to detect fetal aneuploidy. Copy number variations (CNVs) were detected using the Affymetrix SNP Array 6.0 and validated by real time PCR. Global DNA methylation analyses were conducted using a Roche NimbleGen Human DNA Methylation 3x720K Array, and DNA methylation differences were assayed by a Sequenom MassARRAY EpiTYPER. Results: Conventional karyotyping identified 30 cases with aneuploidy in 179 CHD fetuses. Various CNVs were found in two aneuploid fetuses and in five euploid CHD fetuses. Verified segmental deletion or duplications were not directly associated with cardiovascular malformations except in DAAM1 and GATA6. Verifiable aberrant DNA methylation could not be identified in three complex CHD fetuses. Conclusions: In this study, Trisomy 18, Trisomy 21 and 45,XO were the most common aneuploidies identified in CHD fetuses. In the affected samples, only DAAM1 deletion and GATA6 amplification could be associated with cardiovascular biological processes. PMID:23678296

  4. 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

  5. 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

  6. 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

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

    PubMed

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

    2015-08-01

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

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

    E-print Network

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

    1993-10-01

    73 9 35 PGM1 1A,2A 50 31 107 19 75 PGM1 1A,2B 15 3 16 3 18 PGM1 1B,2A 12 6 17 5 12 PGM1 1B,2B 3 0 3 0 0 PGM1 2A,2B 10 4 11 Total 295 131 477 85 283 Allele PGM 1*1 A 0.724 0.699 0.675 0.712 0.678 PGM 1* IB 0.102 0.134 0.100 0.118 0.097 PGM 1...*2, and PGD*C. Significant genetic heterogeneity between populations was demonstrated for the loci RH, MN, ce- rumen, PGD, ABO, GC, GLO, TF, and PGM1. Genetic distance analyses using five loci revealed a lower level of genetic microdif...

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

    PubMed

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

    2014-10-01

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

  10. Pap smear diagnosis using a hybrid intelligent scheme focusing on genetic algorithm based feature selection and nearest neighbor classification.

    PubMed

    Marinakis, Yannis; Dounias, Georgios; Jantzen, Jan

    2009-01-01

    The term pap-smear refers to samples of human cells stained by the so-called Papanicolaou method. The purpose of the Papanicolaou method is to diagnose pre-cancerous cell changes before they progress to invasive carcinoma. In this paper a metaheuristic algorithm is proposed in order to classify the cells. Two databases are used, constructed in different times by expert MDs, consisting of 917 and 500 images of pap smear cells, respectively. Each cell is described by 20 numerical features, and the cells fall into 7 classes but a minimal requirement is to separate normal from abnormal cells, which is a 2 class problem. For finding the best possible performing feature subset selection problem, an effective genetic algorithm scheme is proposed. This algorithmic scheme is combined with a number of nearest neighbor based classifiers. Results show that classification accuracy generally outperforms other previously applied intelligent approaches. PMID:19147127

  11. 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

  12. Genetic diagnosis of familial hypercholesterolaemia: a mutation and a rare non-pathogenic amino acid variant in the same family.

    PubMed

    Naoumova, Rossitza P; Neuwirth, Clare; Pottinger, Bruce; Whittal, Ros; Humphries, Stephen E; Soutar, Anne K

    2004-05-01

    Familial hypercholesterolaemia (FH), a relatively common inherited disorder, is caused by mutations in the gene for the low density lipoprotein (LDL) receptor (LDLR) that result in impaired clearance of LDL. Identification of mutations in patients with the clinical phenotype of FH allows unequivocal diagnosis in potentially affected relatives, but depends critically on distinguishing mutations that affect protein function from variants with no significant effect. A presumed functional mutation in LDLR (G198D in exon 4) was identified in two hypercholesterolaemic English brothers by high throughput screening and was not found in 550 controls. However, a second variant (L458P) was identified separately in their mother that co-segregated with hypercholesterolaemia in the entire pedigree. L458, but not G198, is strongly conserved between species and lies in a region important for beta-propeller stability. G198D was inherited from their normolipidaemic father by two of three siblings heterozygous for L458P; they appeared less severely hypercholesterolaemic and more responsive to statins than the third affected brother and their mother. This study emphasises that apparent co-segregation of an amino acid substitution in a critical region of the protein with hypercholesterolaemia and its absence from a large control population is insufficient evidence that a variant of the LDL receptor is necessarily deleterious to its function. PMID:15135252

  13. 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

  14. 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 ...

  15. Diagnosis of celiac disease

    Microsoft Academic Search

    Shinjini Bhatnagar; Nitya Tandon

    2006-01-01

    Celiac disease is an immune mediated enteropathy initiated by ingestion of gluten, in genetically susceptible individuals.\\u000a With changing epidemiology, celiac disease initially thought to affect only Europeans, has been increasingly reported from\\u000a other parts of the world including India. However, its true prevalence in India is still not known, as the diagnosis is being\\u000a missed. The gold standards for diagnosis

  16. SELECTIVE NEUTRALITY OF GPGD ALLOZYMES IN E. COLZ AND THE EFFECTS OF GENETIC BACKGROUND

    Microsoft Academic Search

    DANIEL DYKHUIZEN; DANIEL L. HARTL

    1980-01-01

    We have used gluconate-limited chemostats to study selective differences between isogenic strains of Escherichia coli RI2 into which four naturally occurring alleles coding for allozymes of 6-phosphogluconate dehydrogenase (6PGD) had been transferred. The limit of detectability of selection with our procedures is a selection coefficient of 0.5%. In the normal E. coli K12 genetic background, all alleles are selectively neutral

  17. High level of genetic differentiation of Juniperus phoenicea (Cupressaceae) in the Mediterranean region: geographic implications

    Microsoft Academic Search

    Adam Boraty?ski; Andrzej Lewandowski; Krystyna Boraty?ska; Jose M. Montserrat; Angel Romo

    2009-01-01

    Fourteen natural populations of Juniperus phoenicea L. from the quite entire species range have been compared using isoenzyme polymorphism. Among 17 loci, 5 (Got1, 6Pgd3, Pgi2, Pgm2 and Shdh2) appeared to be differentiated sufficiently to provide useful information for discrimination between the subspecies phoenicea and turbinata (Guss.) Nyman. Two distinct groups of populations were detected using the Nei’s genetic distance

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

    Microsoft Academic Search

    H. Østergaard; G. Nielsen; H. Johansen

    1985-01-01

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

  19. 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

  20. Learning about Thalassemia

    MedlinePLUS

    ... genetic diagnosis (PGD), used in conjunction with in vitro fertilization, may enable parents who have thalassemia or ... give birth to healthy babies. Embryos created in-vitro are tested for the thalassemia gene before being ...

  1. 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

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

    PubMed Central

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

    2015-01-01

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

  3. Genetic Markers in Blood in a Canadian Eskimo Population with a Comparison of Allele Frequencies in Circumpolar Populations

    Microsoft Academic Search

    Phyllis J. McAlpine; S.-H. Chen; Diane W. Cox; J. B. Dossetor; Eloise Giblett; A. G. Steinberg; Nancy E. Simpson

    1974-01-01

    38 genetically determined marker systems were examined in blood samples obtained from a relatively isolated population of Eskimos living in the Eastern Canadian Arctic. 2,3-DPGM, sGOT, sGPT, PGM1; 6PGD, AcP, E2 cholinesterase, haptoglobin, Gm, Inv, and HL-A were found to exist in polymorphic form, while no variation of the remaining 27 markers was detected in the population. The 2,3-DPGM 2–1

  4. Genetics Home Reference: Fragile X syndrome

    MedlinePLUS

    ... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Fragile X syndrome On this page: Description Genetic changes Inheritance Diagnosis ... names Glossary definitions Reviewed April 2012 What is fragile X syndrome? Fragile X syndrome is a genetic condition that ...

  5. 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

  6. 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 ...

  7. 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 ...

  8. Genetics Home Reference: Breast cancer

    MedlinePLUS

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

  9. Genetics Home Reference: Bladder cancer

    MedlinePLUS

    ... Recent literature OMIM Genetic disorder catalog Conditions > Bladder cancer On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed January 2007 What is bladder cancer? Bladder cancer is a disease in which certain ...

  10. Genetics Home Reference: Blau syndrome

    MedlinePLUS

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

  11. Genetics Home Reference: Systemic scleroderma

    MedlinePLUS

    ... Recent literature OMIM Genetic disorder catalog Conditions > Systemic scleroderma On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed April 2015 What is systemic scleroderma? Systemic scleroderma is an autoimmune disorder that affects ...

  12. 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 ...

  13. Increasing Live Birth Rate by Preimplantation Genetic Screening of Pooled Polar Bodies Using Array Comparative Genomic Hybridization

    PubMed Central

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

    2015-01-01

    Meiotic errors during oocyte maturation are considered the major contributors to embryonic aneuploidy and failures in human IVF treatment. Various technologies have been developed to screen polar bodies, blastomeres and trophectoderm cells for chromosomal aberrations. Array-CGH analysis using bacterial artificial chromosome (BAC) arrays is widely applied for preimplantation genetic diagnosis (PGD) using single cells. Recently, an increase in the pregnancy rate has been demonstrated using array-CGH to evaluate trophectoderm cells. However, in some countries, the analysis of embryonic cells is restricted by law. Therefore, we used BAC array-CGH to assess the impact of polar body analysis on the live birth rate. A disadvantage of polar body aneuploidy screening is the necessity of the analysis of both the first and second polar bodies, resulting in increases in costs for the patient and complex data interpretation. Aneuploidy screening results may sometimes be ambiguous if the first and second polar bodies show reciprocal chromosomal aberrations. To overcome this disadvantage, we tested a strategy involving the pooling of DNA from both polar bodies before DNA amplification. We retrospectively studied 351 patients, of whom 111 underwent polar body array-CGH before embryo transfer. In the group receiving pooled polar body array-CGH (aCGH) analysis, 110 embryos were transferred, and 29 babies were born, corresponding to live birth rates of 26.4% per embryo and 35.7% per patient. In contrast, in the control group, the IVF treatment was performed without preimplantation genetic screening (PGS). For this group, 403 embryos were transferred, and 60 babies were born, resulting in live birth rates of 14.9% per embryo and 22.7% per patient. In conclusion, our data show that in the aCGH group, the use of aneuploidy screening resulted in a significantly higher live birth rate compared with the control group, supporting the benefit of PGS for IVF couples in addition to the suitability and effectiveness of our polar body pooling strategy. PMID:26024488

  14. 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 ...

  15. Fault diagnosis using hybrid artificial intelligent methods

    Microsoft Academic Search

    Yann-Chang Huang; Chao-Ming Huang; Huo-Ching Sun; Yi-Shi Liao

    2010-01-01

    This paper presents genetic-based neural networks (GNNs) for fault diagnosis of power transformers. The GNNs automatically tune the network parameters, connection weights and bias terms of the neural networks, to yield the best model according to the proposed genetic algorithm. Due to the global search capabilities of the genetic algorithm and the highly nonlinear mapping nature of the neural networks,

  16. Contrasting patterns of spatial genetic structure of diploid and triploid populations of the clonal aquatic species, Butomus umbellatus (Butomaceae) , in Central Europe

    Microsoft Academic Search

    Jan Kirschner; Igor Bartish; Zdenka Hroudová; Lída Kirschnerová; Petr Zákravský

    2004-01-01

    Genetic diversity in a sample of an aquatic plantButomus umbellatus from 37 localities in Czechia and Slovakia was studied by analyzing six polymorphic loci in three enzymatic systems (SKDH,\\u000a PGD and AAT). Diversity among ramets was low in eight populations with relatively extensive sampling (only one population\\u000a possessed more than one multilocus genotype), suggesting high clonality of reproduction in these

  17. Genetics Home Reference: Hypophosphatasia

    MedlinePLUS

    ... by a softening of the bones known as osteomalacia. In adults, recurrent fractures in the foot and ... Hypophosphatasia Genetic Testing Registry: Infantile hypophosphatasia MedlinePlus Encyclopedia: Osteomalacia You might also find information on the diagnosis ...

  18. 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

  19. Prostaglandin (PG)D(2) and 15-deoxy-Delta(12,14)-PGJ(2), but not PGE(2), mediate shear-induced chondrocyte apoptosis via protein kinase A-dependent regulation of polo-like kinases.

    PubMed

    Zhu, F; Wang, P; Kontrogianni-Konstantopoulos, A; Konstantopoulos, K

    2010-08-01

    Excessive mechanical loading of cartilage producing hydrostatic stress, tensile strain and fluid flow leads to chondrocyte apoptosis and osteoarthritis. High fluid flow induces cyclooxygenase-2 (COX-2) expression in sheared chondrocytes, which suppresses their antioxidant capacity and contributes to apoptosis. The pivotal role of COX-2 in shear-induced chondrocyte apoptosis and the conflicting literature data on the roles of prostaglandin (PG)E(2), PGD(2) and its metabolite 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) in chondrocyte apoptosis prompted us to analyze which COX-2-derived PG is involved in this process. We show that exogenously added PGD(2) and 15d-PGJ(2), but not PGE(2), diminish the viability of human T/C-28a2 chondrocytes under static conditions. In agreement with these observations, knockdown of L-PGD synthase (L-PGDS) abolishes shear-induced chondrocyte apoptosis. Using cDNA microarrays in conjunction with clustering algorithms, we propose a novel signaling pathway by which high fluid shear mediates COX-2/L-PGDS-dependent chondrocyte apoptosis, which is validated by molecular interventions. We show that L-PGDS controls the downregulation of protein kinase A (PKA), which in turn regulates Polo-like kinase1 (Plk1) and Plk3. Plks target p53, which controls the transcription of p53 effectors (TP53INPs, FAS and Bax) involved in chondrocyte apoptosis. Reconstructing the signaling network regulating chondrocyte apoptosis may provide insights to optimize conditions for culturing artificial cartilage in bioreactors and for developing therapeutic strategies for arthritic disorders. PMID:20150912

  20. Integrated study of 100 patients with Xp21 linked muscular dystrophy using clinical, genetic, immunochemical, and histopathological data. Part 3. Differential diagnosis and prognosis.

    PubMed Central

    Nicholson, L V; Johnson, M A; Bushby, K M; Gardner-Medwin, D; Curtis, A; Ginjaar, I B; den Dunnen, J T; Welch, J L; Butler, T J; Bakker, E

    1993-01-01

    This report is the third part of a trilogy from a multidisciplinary study which was undertaken to investigate gene and protein expression in a large cohort of patients with well defined and diverse clinical phenotypes. The aim of part 3 was to review which of the analytical techniques that we had used would be the most useful for differential diagnosis, and which would provide the most accurate indication of disease severity. Careful clinical appraisal is very important and every DMD patient was correctly diagnosed on this basis. In contrast, half of the sporadic BMD patients and all of the sporadic female patients had received different tentative diagnoses based on clinical assessments alone. Sequential observations of quantitative parameters (such as the time taken to run a fixed distance) were found to be useful clinical indicators for prognosis. Intellectual problems might modify the impression of physical ability in patients presenting at a young age. Histopathological assessment was accurate for DMD but differentiation between BMD and other disorders was more difficult, as was the identification of manifesting carriers. Our data on a small number of women with symptoms of muscle disease indicate that abnormal patterns of dystrophin labelling on sections may be an effective way of differentiating between female patients with a form of limb girdle dystrophy and those carrying a defective Xp21 gene. Dystrophin gene analysis detects deletions/duplications in 50 to 90% of male patients and is the most effective non-invasive technique for diagnosis. Quantitative Western blotting, however, would differentiate between all Xp21 and non-Xp21 male patients. In this study we found a clear relationship between increased dystrophin abundance (determined by densitometric analysis of blots) and clinical condition, with a correlation between dystrophin abundance and the age at loss of independent mobility among boys with DMD and intermediate D/BMD. This indicates that blotting is the most sensitive and accurate technique for diagnosis and prognosis. Images PMID:8411069

  1. From diagnosis to social diagnosis.

    PubMed

    Brown, Phil; Lyson, Mercedes; Jenkins, Tania

    2011-09-01

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

  2. Genetics of Sudden Cardiac Death

    Microsoft Academic Search

    Alon Barsheshet; Andrew Brenyo; Arthur J. Moss; Ilan Goldenberg

    Advances in genetic testing technology have led to a proliferation of new genetic tests and accelerated developments in the\\u000a field of cardiovascular genetic medicine. These advances enhance presymptomatic diagnosis and can establish a definitive molecular\\u000a diagnosis for symptomatic patients at risk for sudden cardiac death. Most importantly, genotype-phenotype correlations can\\u000a add important information for predicting outcome and selecting treatment for

  3. 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

  4. Autoinflammatory syndromes: diagnosis and management

    Microsoft Academic Search

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

    2010-01-01

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

  5. Homozygous SMN1 exons 1-6 deletion: pitfalls in genetic counseling and general recommendations for spinal muscular atrophy molecular diagnosis.

    PubMed

    Thauvin-Robinet, C; Drunat, S; Saugier Veber, P; Chantereau, D; Cossée, M; Cassini, C; Soichot, P; Masurel-Paulet, A; De Monléon, J V; Sagot, P; Huet, F; Antin, M; Calmels, N; Faivre, L; Gérard, B

    2012-07-01

    We report on a rare homozygous intragenic deletion encompassing exons 1-6 of the SMN1 gene in a patient with spinal muscular atrophy (SMA) born into a consanguineous family. This exceptional configuration induced misinterpretation of the molecular defect involved in this patient, who was first reported as having a classic SMN1 exon 7 deletion. This case points out the possible pitfalls in molecular diagnosis of SMA in affected patients and their relatives: exploration of the SMN1 exon 7 (c.840C/T alleles) may be disturbed by several non-pathological or pathological variants around the SMN1 exon 7. In order to accurately describe the molecular defect in an SMA-affected patient, we propose to apply the Human Genome Variation Society nomenclature. This widely accepted nomenclature would improve the reporting of the molecular defect observed in SMA patients and thus would avoid the commonly used but imprecise terminology "absence of SMN1 exon 7." PMID:22678974

  6. 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.

  7. Genetics Home Reference: Acute promyelocytic leukemia

    MedlinePLUS

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

  8. Genetics Home Reference: Congenital diaphragmatic hernia

    MedlinePLUS

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

  9. Genetics Home Reference: Lafora progressive myoclonus epilepsy

    MedlinePLUS

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

  10. 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 ...

  11. Genetics Home Reference: Atelosteogenesis type 1

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > Atelosteogenesis type 1 On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed September 2011 What is atelosteogenesis type 1? Atelosteogenesis type 1 is a disorder that affects ...

  12. Genetics Home Reference: Type 1 diabetes

    MedlinePLUS

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

  13. Genetics Home Reference: Hereditary diffuse gastric cancer

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Hereditary diffuse gastric cancer On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed January 2014 What is hereditary diffuse gastric cancer? Hereditary diffuse gastric cancer (HDGC) is an inherited ...

  14. 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 ...

  15. Genetics Home Reference: Diamond-Blackfan anemia

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > Diamond-Blackfan anemia On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed February 2012 What is Diamond-Blackfan anemia? Diamond-Blackfan anemia is a disorder of the ...

  16. Genetics Home Reference: Intrahepatic cholestasis of pregnancy

    MedlinePLUS

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

  17. Genetics Home Reference: Giant axonal neuropathy

    MedlinePLUS

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

  18. 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.

  19. Parental decisions following the prenatal diagnosis of sex chromosome abnormalities

    Microsoft Academic Search

    Hanan A Hamamy; Sophie Dahoun

    2004-01-01

    Objective: To report parental decisions regarding pregnancy termination following the prenatal diagnosis of a sex chromosome abnormality (SCA) in the fetus. Methods: Retrospective collection of data from records of 61 families receiving genetic counseling after prenatal diagnosis of a sex chromosome abnormality in the fetus in the Division of Medical Genetics, University Hospital of Geneva during the time period 1980–2001.

  20. 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

  1. 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

  2. Genetics and epilepsy

    PubMed Central

    Steinlein, Ortrud K.

    2008-01-01

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

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

    PubMed

    Shu, Bowen; Zhang, Chunsun; Xing, Da

    2015-06-01

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

  4. Genetic diagnosis of community-acquired MRSA: a multiplex real-time PCR method for Staphylococcal cassette chromosome mec typing and detecting toxin genes.

    PubMed

    Motoshima, Maiko; Yanagihara, Katsunori; Morinaga, Yoshitomo; Matsuda, Junichi; Sugahara, Kazuyuki; Yamada, Yasuaki; Kohno, Shigeru; Kamihira, Shimeru

    2010-02-01

    Methicillin-resistant Staphylococcus aureus (MRSA) causes a wide range of infections in health care settings and community environments. In particular, community-acquired MRSA (CA-MRSA) is important for clinicians because many fatal cases in healthy populations have been reported. Staphylococcal cassette chromosome mec (SCCmec) is a mobile genetic element and carries the central determinant for broad-spectrum beta-lactam resistance encoded by the mecA gene. The emergence of MRSA is due to the acquisition and insertion of the SCCmec element into the chromosome. CA-MRSA is characterized as SCCmec type IV. Thus, we aimed to establish a novel multiplex real-time PCR method to distinguish SCCmec type, which enables us to evaluate the pathogenicity of MRSA. A total of 778 MRSA were isolated at Nagasaki University Hospital from 2000 to 2007. All isolates were subjected to minimal inhibitory concentration testing and PCR for SCCmec typing and detecting genes of toxins: tst (toxic shock syndrome toxin 1), sec (encoded enterotoxin type c), etb (exfoliative toxin type b), and lukS/F-PV (Panton-Valentine leukocidin). PCR was performed to amplify a total of 10 genes in the same run. The 667 MRSA clones detected from pus in 778 clones were classified as SCCmec type II (77.7%), type IV (19.2%), and type I (3.0%). 87.5% of SCCmec type II clone had tst and sec genes. No isolate was lukS/F-PV positive. The present study indicates the high rate of lukS/F-PV-negative SCCmec type IV in Nagasaki. Our PCR method is convenient for typing MRSA and detecting toxins in Japan. PMID:20139668

  5. The genetics of the epilepsies.

    PubMed

    El Achkar, Christelle M; Olson, Heather E; Poduri, Annapurna; Pearl, Phillip L

    2015-07-01

    While genetic causes of epilepsy have been hypothesized from the time of Hippocrates, the advent of new genetic technologies has played a tremendous role in elucidating a growing number of specific genetic causes for the epilepsies. This progress has contributed vastly to our recognition of the epilepsies as a diverse group of disorders, the genetic mechanisms of which are heterogeneous. Genotype-phenotype correlation, however, is not always clear. Nonetheless, the developments in genetic diagnosis raise the promise of a future of personalized medicine. Multiple genetic tests are now available, but there is no one test for all possible genetic mutations, and the balance between cost and benefit must be weighed. A genetic diagnosis, however, can provide valuable information regarding comorbidities, prognosis, and even treatment, as well as allow for genetic counseling. In this review, we will discuss the genetic mechanisms of the epilepsies as well as the specifics of particular genetic epilepsy syndromes. We will include an overview of the available genetic testing methods, the application of clinical knowledge into the selection of genetic testing, genotype-phenotype correlations of epileptic disorders, and therapeutic advances as well as a discussion of the importance of genetic counseling. PMID:26008807

  6. How Are Genetic Conditions Diagnosed?

    MedlinePLUS

    ... geneticists and other healthcare providers. The Agency for Healthcare Research and Quality’s (AHRQ) National Guideline Clearinghouse has compiled screening, diagnosis, treatment, and management guidelines for many genetic disorders. GeneReviews , a resource ...

  7. Genetics Home Reference: Troyer syndrome

    MedlinePLUS

    ... treatment providers. Gene Review: Hereditary Spastic Paraplegia Overview Gene Review: Troyer Syndrome Genetic Testing Registry: Troyer syndrome Spastic Paraplegia Foundation, Inc.: Treatments and Therapies You might also find information on the diagnosis ...

  8. Genetics: advances in genetic testing for deafness

    PubMed Central

    Shearer, A. Eliot; Smith, Richard J.H.

    2013-01-01

    Purpose of review To provide an update on recently discovered human deafness genes and to describe advances in comprehensive genetic testing platforms for deafness, both of which have been enabled by new massively parallel sequencing technologies. Recent findings Over the review period, three syndromic and six nonsyndromic deafness genes have been discovered, bringing the total number of nonsyndromic deafness genes to 64. Four studies have shown the utility of massively parallel sequencing for comprehensive genetic testing for deafness. Three of these platforms have been released on a clinical or commercial basis. Summary Deafness is the most common sensory deficit in humans. Genetic diagnosis has traditionally been difficult due to extreme genetic heterogeneity and a lack of phenotypic variability. For these reasons, comprehensive genetic screening platforms have been developed with the use of massively parallel sequencing. These technologies are also accelerating the pace of gene discovery for deafness. Because genetic diagnosis is the basis for molecular therapies, these advances lay the foundation for the clinical care of deaf and hard-of-hearing persons in the future. PMID:23042251

  9. 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.

  10. The value of cardiac genetic testing.

    PubMed

    Ingles, Jodie; Semsarian, Christopher

    2014-08-01

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

  11. Diagnosis of Sarcoidosis.

    PubMed

    Wessendorf, Thomas E; Bonella, Francesco; Costabel, Ulrich

    2015-08-01

    The diagnosis of sarcoidosis, a systemic granulomatous disease, is based on a compatible clinical-radiological picture and the histological evidence of noncaseating granulomas. Other diseases mimicking sarcoidosis, mostly infections and other granulomatoses, have to be excluded. There is no single test for sarcoidosis, and the presence of granulomas alone does not establish the diagnosis. Symptoms of sarcoidosis are not specific and can be markedly different according to organ involvement and disease course. Respiratory symptoms and fatigue are the most common symptoms at any stage of disease. Histological confirmation is not needed for Löfgren's or Heerfordt's syndrome and asymptomatic bihilar lymphadenopathy. The radiological staging system is still based on chest radiography, and computed tomography is not mandatory for routine follow-up. (18)F-fluorodeoxyglucose positron emission tomography may be of value in special cases. For assessment of lung involvement and follow-up, pulmonary function tests are necessary with vital capacity being the most important single parameter and diffusion capacity the most sensitive. Bronchoscopy with biopsy is the most common procedure for detection of granulomas, when there is no easier biopsy site like skin or peripheral lymph nodes. Endobronchial ultrasonography-guided transbronchial needle aspiration has replaced mediastinoscopy for evaluation of mediastinal and hilar lymph nodes with a high diagnostic yield. Despite numerous studies, no single biomarker can be reliably used for correct diagnosis or exclusion of sarcoidosis. Genetic testing, despite promising advances, has still not been included in routine care for sarcoidosis patients. The long-term prognosis of sarcoidosis depends on the different organ manifestations: Cardiac or central nervous involvement, together with respiratory complications, is critical. A multidisciplinary approach is necessary for comprehensive care of the sarcoidosis patient. PMID:25779004

  12. Genetic history of the population of Puglia (southern Italy).

    PubMed

    Rickards, O; Scano, G; Martinez-Labarga, C; Taraborelli, T; Gruppioni, G; De Stefano, G F

    1995-04-01

    Nine-hundred and twenty-two individuals belonging to the five provinces of Puglia were typed for nine erythrocyte genetic markers (ACP1, ADA, AK1, ESD, GLO1, PGD, PGM1, PGM2, and SODA). Genetic heterogeneity within Puglia was investigated on the basis of allele frequencies of the above mentioned markers plus ABO*A, ABO*B, ABO*O, and RH*D, by the (chi 2 test and Rst statistic. The analyses revealed no differences at the provincial level. Furthermore, correspondence and genetic distance analyses were applied to look for a statistical difference within Puglia from different standpoints, as well as between Puglia, the rest of Italy and other European and Near and Middle Eastern populations whose genetic history is most likely related. Southern and central Italian, Greek and Aegean populations appeared very homogeneous and quite differentiated from the rest of Europe, both continental (including northern Italy) and south-eastern, stressing the major impact of the heavy Greek colonization on the genetic pools of the circum-Mediterranean people. PMID:8845336

  13. Genetics Home Reference: Autoimmune polyglandular syndrome, type 1

    MedlinePLUS

    ... Genetic disorder catalog Conditions > Autoimmune polyglandular syndrome, type 1 On this page: Description Genetic changes Inheritance Diagnosis ... August 2007 What is autoimmune polyglandular syndrome, type 1? Autoimmune polyglandular syndrome, type 1 is an inherited ...

  14. Genetics Home Reference: X-linked chondrodysplasia punctata 1

    MedlinePLUS

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

  15. Genetics Home Reference: Leukocyte adhesion deficiency type 1

    MedlinePLUS

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

  16. 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 ...

  17. Genetics Home Reference: Iron-refractory iron deficiency anemia

    MedlinePLUS

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

  18. Genetics Home Reference: X-linked sideroblastic anemia

    MedlinePLUS

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

  19. 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

  20. Diagnosis and evaluation of hypogonadism.

    PubMed

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

    2014-02-01

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

  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. 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 ...

  3. Prenatal diagnosis for risk of spinal muscular atrophy

    Microsoft Academic Search

    I Cuscó; M. J Barceló; C Soler; J Parra; M Baiget; E Tizzano

    2002-01-01

    ObjectivesPrenatal diagnosis of spinal muscular atrophy is usually performed in high risk couples by detection of a homozygous deletion in the survival motor neurone gene (SMN1). However, other relatives at risk of being carriers very often request genetic counselling and the possibility of prenatal diagnosis. The aim of this study was to validate a SMN1 gene quantitative test to help

  4. [The Dagestan gene pool: analysis of the frequencies of classical genetic markers in Avars].

    PubMed

    Radzhabov, M O; Mamaev, I A; Shamov, I A; Gasaev, D G; Shil'nikova, I N; Shne?der, Iu V

    2010-04-01

    This study is part of long-term research in the gene pool of Dagestan ethnic groups. The phenotype (in percent), gene, and haplotype frequencies in three Avar populations are reported. A total of 37 alleles of 13 loci of immune and biochemical genetic marker systems (ABO, Rhesus, P, Lewis, HP, GC, C'3, TF, 6PGD, GLO1, ESD, ACP, and PGM1) have been studied. Rare haplotypes of the Rhesus system (CDE, Cde, and cdE) have been found in the populations studied. In two out of three local populations (Khunzakh and Kharakhi), a typically "Caucasoid" rare gene ACP1c of the AcP1 locus has proved to be relatively frequent (0.030 and 0.023, respectively). The frequencies of the allele variants P2, le, and Hp1 of loci of the P, Lewis, and HP systems, respectively, have been found to be lower than in other Caucasian ethnic groups and the total northern Eurasian population. The mean allele frequencies for the GC, C'3, TF, 6PGD, GLO1, and ESD systems in the populations studied are comparable wit those for both Caucasian ethnic groups and the total population of the European historical ethnographic province. Statistical analysis of the results has shown 11 cases of significant deviations of the observed phenotype frequencies from the Hardy-Weinberg equilibrium. PMID:20536025

  5. Medical genetics

    SciTech Connect

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

    1989-01-01

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

  6. [Psychosis: from diagnosis to syndrome].

    PubMed

    van Os, Jim; Kapur, Shitij

    2010-01-01

    Psychotic disorders such as schizophrenia are associated with severe psychological suffering for the patient and high healthcare costs. The initial symptoms typically emerge in adolescence and early adulthood. The incidence varies considerably from place to place and among different groups of immigrants. The symptoms, clinical course, and treatment response differs per individual. Genetic vulnerability for psychotic disorders is shared in part with bipolar disorder, and recent molecular genetic findings also indicate an overlap with developmental disorders such as autism. The diagnosis of schizophrenia is associated with demonstrable alterations in brain structure and changes in dopamine neurotransmission, the latter being directly related to hallucinations and delusions. Antipsychotics, which block the dopamine system, are effective for delusions and hallucinations but less so for disabling cognitive and motivational impairments. A better understanding of the biological mechanisms and the psychosocial factors underlying psychotic disorders may contribute to new treatments. PMID:20456790

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

    PubMed

    Gehring; Delph

    1999-06-01

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

  8. Genetics Home Reference: Gastrointestinal stromal tumor

    MedlinePLUS

    ... cells in the gastrointestinal tract and patches of dark skin on various areas of the body. Some ... Cancer Society: Treating Gastrointestinal Stromal Tumor (GIST) Cancer.Net: Gastrointestinal Stromal Tumor--Diagnosis Genetic Testing Registry: Gastrointestinal ...

  9. 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 ...

  10. 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 ...

  11. [Diagnosis and approach in suspected ankylosing spondylitis].

    PubMed

    Rentsch, H U; van der Linden, S; Gerber, N

    1991-05-21

    The time interval from first clinical symptoms to definite diagnosis of ankylosing spondylitis (Morbus Bechterew) is still too long. Thus, many years for essential therapeutic interventions are unequivocally lost. Therefore, it is most important to improve early diagnosis. To this aim the diagnostic criteria recently suggested by van der Linden are useful in relatively early stages of disease (table 1). Diagnosis is based on patient history, clinical examination and radiological signs of sacroiliitis. Blood examinations for ESR, rheumatoid factors and antinuclear antibodies are important with regard to differential diagnosis. The determination of the HLA-B27 haplotype as a diagnostic tool is irrelevant on terms of single cases, because at least 8% of ankylosing spondylitis patients are HLA-B27-negative and in middle europe at least 7% of normal controls exhibit this genetic marker. PMID:2052824

  12. CHIPS for genetic testing to improve a regional clinical genetic service.

    PubMed

    Niida, Y; Ozaki, M; Inoue, M; Takase, E; Kuroda, M; Mitani, Y; Okumura, A; Yokoi, A; Fujita, S; Yamada, K

    2015-08-01

    In current practice of clinical genetics, molecular diagnosis has become more widely used than ever before. DNA diagnosis is important for appropriate medical care of the patient, and proper genetic counseling to the family. However, genetic testing of orphan disease cannot always be performed easily. In multiple congenital anomalies (MCA) syndromes by monogenic cause, the broad mutational spectrum and large size of responsible genes often make molecular diagnosis expensive and cumbersome. We solve this problem with on-demand genetic testing by CHIPS (CEL nuclease mediated heteroduplex incision with polyacrylamide gel electrophoresis and silver staining) technology, which is the ultimately conventional and economical mutation screening system. In this article, we show eight patients with MCA syndromes who were recently treated at our hospital, and demonstrate that CHIPS successfully offers efficient and inexpensive genetic testing and facilitates clinical genetic service in our local region. PMID:25046119

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

    Cancer.gov

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

  14. Prenatal diagnosis in congenital contractural arachnodactyly.

    PubMed

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

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

  15. [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

  16. Genetic algorithms

    NASA Technical Reports Server (NTRS)

    Wang, Lui; Bayer, Steven E.

    1991-01-01

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

  17. Celiac disease: diagnosis and management.

    PubMed

    Pelkowski, Timothy D; Viera, Anthony J

    2014-01-15

    Celiac disease is an autoimmune disorder of the gastrointestinal tract. It is triggered by exposure to dietary gluten in genetically susceptible individuals. Gluten is a storage protein in wheat, rye, and barley, which are staples in many American diets. Celiac disease is characterized by chronic inflammation of the small intestinal mucosa, which leads to atrophy of the small intestinal villi and subsequent malabsorption. The condition may develop at any age. Intestinal manifestations include diarrhea and weight loss. Common extraintestinal manifestations include iron deficiency anemia, decreased bone mineral density, and neuropathy. Most cases of celiac disease are diagnosed in persons with extraintestinal manifestations. The presence of dermatitis herpetiformis is pathognomonic for celiac disease. Diagnosis is supported by a positive tissue transglutaminase serologic test but, in general, should be confirmed by a small bowel biopsy showing the characteristic histology associated with celiac disease. The presence of human leukocyte antigen alleles DQ2, DQ8, or both is essential for the development of celiac disease, and can be a useful genetic test in select instances. Treatment of celiac disease is a gluten-free diet. Dietary education should focus on identifying hidden sources of gluten, planning balanced meals, reading labels, food shopping, dining out, and dining during travel. About 5% of patients with celiac disease are refractory to a gluten-free diet. These patients should be referred to a gastroenterologist for reconsideration of the diagnosis or for aggressive treatment of refractory celiac disease, which may involve corticosteroids and immunomodulators. PMID:24444577

  18. Genetic counseling for psychiatric disorders

    Microsoft Academic Search

    Debby W. Tsuang; Stephen V. Faraone; Ming T. Tsuang

    2001-01-01

    Like other medical conditions, some psychiatric disorders are inherited, whereas others are not. Human genetics research is\\u000a moving at a rapid pace. Genes for over 450 genetic disorders have been cloned and many disease-causing mutations have also\\u000a been identified. The explosion of this new knowledge has created many new exciting opportunities in the diagnosis of these\\u000a heritable disorders. The rapid

  19. 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

  20. Genetic Algorithms

    Microsoft Academic Search

    Kumara Sastry; David Goldberg; Graham Kendall

    Genetic algorithms (GAs) are search methods based on principles of natural selection and genetics (Fraser, 1957;Bremermann, 1958;Holland, 1975). We start with a brief introduction to simple genetic algorithms and associated terminology.

  1. Genetic Counseling

    MedlinePLUS

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

  2. Reliability of headache diagnosis

    Microsoft Academic Search

    Ira Daniel Turkat; Phillip J. Brantley; Keith Orton; Henry E. Adams

    1981-01-01

    The literature on diagnosis of head pain associated with psychological factors indicates that these diagnoses rely almost exclusively on self-report criteria. The reliability of self-report criteria for diagnosis of headache has not been previously reported. The present study investigated the reliability of headache diagnosis based on the criteria suggested by the Ad Hoc Committee on Classification of Headache. The results

  3. 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

  4. 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

  5. Genetics of man, 2nd ed

    SciTech Connect

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

    1986-01-01

    New information in this book centers on DNA technology and its clinical application, progress in pre-natal diagnosis, teratogenic syndromes, immunogenetics, and cancer genetics. Normal and abnormal human genetic variations are detailed, along with methods of assessing their genetic components. The book then explains the ways in which this information is applicable to genetic counseling, the management of hereditary disease, and other social and ethical issues. Incorporating basic genetic principles, this referenced text is augmented by a glossary, illustrations and photographs, and an appendix of Chromosome Band Nomenclature.

  6. Genetics Home Reference: Genetic Consultation

    MedlinePLUS

    ... Mutations and Health Inheritance Traits Consultation Testing Therapy Human Genome Project Genomic Research Precision Medicine Next Handbook > Genetic Consultation Finding and visiting a genetic counselor or ...

  7. Developmental ability of chromosomally abnormal human embryos to develop to the blastocyst stage

    Microsoft Academic Search

    M. Sandalinas; S. Sadowy; M. Alikani; G. Calderon; J. Cohen

    2001-01-01

    BACKGROUND: A correlation between morphology, developmental competence and chromosome abnormalities is established. However, since absolute correlations are rare, embryo selection remains one of the most arduous tasks in assisted reproduction. This study was undertaken in order to determine which chromosomal abnormalities are compatible with development to the blastocyst stage. METHODS: Embryos diagnosed by preimplantation genetic diagnosis (PGD) as chromosomally abnormal

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

    ERIC Educational Resources Information Center

    Kauffman, James M.; Hallahan, Daniel P.

    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…

  9. Genetic Diseases and Associated Urologic Manifestations

    Microsoft Academic Search

    Jeffrey S. Palmer; Katherine C. Hubert

    \\u000a The diagnosis of a genetic disease is usually made through a combination of clinical characteristics and genetic testing.\\u000a It is important that urologists be able to recognize the cardinal features of these disorders and identify the associated\\u000a urologic manifestations. The purpose of this chapter is to provide an overview of the genetic disorders with urologic manifestations.

  10. Genetic determinants of cardiac hypertrophy

    PubMed Central

    Marian, Ali J.

    2009-01-01

    Purpose of review Cardiac hypertrophy is a common phenotypic response of the heart to stimulants. It is associated with increased morbidity and mortality in various cardiovascular disorders. Genetic factors are important determinants of phenotypic expression of cardiac hypertrophy, whether in single-gene disorders or in complex traits. We focus on the molecular genetics of cardiac hypertrophy in various conditions with an emphasis on hypertrophic cardiomyopathy, a genetic paradigm of cardiac hypertrophic response. Recent findings The molecular genetic basis of cardiac hypertrophy in single-gene disorders has been partially elucidated. Likewise, the impact of genetics on the expression of cardiac hypertrophy in the general population has been demonstrated. Identification of mutations in the Z disk proteins has expanded the spectrum of causal mutations beyond the thin and thick filaments of the sarcomeres. In addition, modifier loci have been mapped and shown to impart considerable effects on the expression of cardiac hypertrophy in hypertrophic cardiomyopathy. Elucidation of the molecular genetics of sarcomeric hypertrophic cardiomyopathy and many of the phenocopies has highlighted the limitations of clinical diagnosis as a determinant of management and prognostic advice. The findings have raised the importance of diagnosis and treatment algorithms, which are based on both genotype and phenotype information. Summary Cardiac hypertrophy, regardless of the cause, is the phenotypic consequence of complex interactions between genetic and nongenetic factors. PMID:18382207

  11. Genetic Algorithms Genetic Programming

    E-print Network

    ] F. H. Bennett III, J. R. Koza, D. Andre, and M. A. Keane, Evolution of a 60 Decibel OP Amp using) Configuration Bit Stream Bennett III #12;rossover mutation rossover Mutation crossover . crossover point transactions on evolutionary computation, vol3, no 3, pp. 220-235, september 1999. [2] Koza, J. R., Genetic

  12. 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

  13. Antenatal diagnosis of lethal skeletal dysplasias.

    PubMed

    Tretter, A E; Saunders, R C; Meyers, C M; Dungan, J S; Grumbach, K; Sun, C C; Campbell, A B; Wulfsberg, E A

    1998-02-17

    Lethal skeletal dysplasias (LSD) are a heterogeneous group of rare but important genetic disorders characterized by abnormal growth and development of bone and cartilage. We describe the diagnosis and outcome of 29 cases of lethal skeletal dysplasias evaluated between January 1989 and December 1996 at the University of Maryland Medical Center and the Ultrasound Institute of Baltimore. Two cases presented at delivery with no prenatal care while the remaining 27 cases were identified by antenatal sonography. Final diagnoses included thanatophoric dysplasia (14), osteogenesis imperfecta, type II (6), achondrogenesis (2), short rib syndromes (3), campomelic syndrome (2), atelosteogenesis (1), and no evidence of a skeletal dysplasia (1). Twenty out of 27 pregnancies were terminated with an average at detection of 21.6 weeks. The other 7 pregnancies that went on to deliver had an average age at detection of 29.2 weeks. Fetal abnormalities in the terminated pregnancies were identified at a significantly earlier gestational age (P = 0.0016) than the pregnancies that continued. While the identification of LSD by sonography was excellent (26/27), only 13/27 (48%) were given an accurate specific antenatal diagnosis. In 8/14 (57%) cases with an inaccurate or nonspecific diagnosis there was a significant or crucial change in the genetic counseling. Thus, while antenatal sonography is an excellent method for discovering LSD, clinical examination, radiographs, and autopsy are mandatory for making a specific diagnosis. PMID:9489797

  14. [Differential diagnosis of hearing disorders].

    PubMed

    Schulze, A; Zahnert, T

    2014-10-01

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

  15. Differential diagnosis of Alzheimer's disease.

    PubMed

    Geldmacher, D S; Whitehouse, P J

    1997-05-01

    Accurate diagnosis of dementia is essential to provide appropriate treatment as well as patient and family counseling. It may be difficult to differentiate dementia from delirium. In addition, several features distinguish dementia from depression, but the two can coexist and the distinction may be uncertain. Dementias can be grouped into two categories: dementia that presents without prominent motor signs and dementia that presents with prominent motor signs. Dementias without prominent motor signs include Alzheimer's disease, frontotemporal dementia, and Creutzfeld-Jakob and other prion diseases. Dementias characterized at onset by prominent motor signs include dementias with Lewy bodies, idiopathic Parkinson's disease, progressive supranuclear palsy, cortico-basal ganglionic degeneration, hydrocephalus, Huntington's disease, and vascular dementia. Routine diagnostic steps include a careful history, mental status screening, laboratory and imaging studies, and neuropsychologic testing. Genetic testing is available, but its use is controversial and raises complex ethical questions. PMID:9153154

  16. Enterobiasis (Pinworm Infection): Diagnosis

    MedlinePLUS

    ... Holidays Contact CDC-INFO Pinworm Infection General Information Pinworm Infection FAQs Epidemiology & Risk Factors Biology Disease Diagnosis Treatment Prevention & Control Resources for Health Professionals Publications Information ...

  17. [Diagnosis and differential diagnosis of swollen leg].

    PubMed

    Ludwig, M; Vetter, H

    1989-09-12

    Leg swelling is often of edematous nature. The most important differential diagnosis lies in the distinction between venous or lymphatic forms of edema. An increased vascular permeability and alterations in blood composition have also to be taken into account. A particular entity is the lipedema. Next to an accurate history, specific inspection and palpatory criteria permit to distinguish the various forms. Tests for venous function, laboratory and technologically investigative techniques increase diagnostic accuracy. Lymphedema can only be diagnosed by an exact clinical diagnosis. PMID:2678371

  18. 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

  19. Response to varicocelectomy in oligospermic men with and without defined genetic infertility

    Microsoft Academic Search

    Selahittin Cayan; Douglas Lee; Lauri D Black; Renee A Reijo Pera; Paul J Turek

    2001-01-01

    Objectives. To compare the clinical characteristics of infertile men who have varicocele with and without a genetic anomaly, and report the results of varicocelectomy in these two cohorts of men.Methods. Study subjects included 33 men who underwent genetic counseling and testing for a diagnosis of oligospermia with varicocele. Seven men were diagnosed with coexisting genetic infertility (genetic [+]; abnormal karyotype

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. SOYBEAN GENETICS

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  6. Preimplantation Genetic Testing: Indications and Controversies

    PubMed Central

    Cooper, Amber R.; Jungheim, Emily S.

    2014-01-01

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

  7. Advances in human genetics

    SciTech Connect

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

    1993-01-01

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

  8. 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 & ...

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

    Microsoft Academic Search

    D. Pareyson

    2004-01-01

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

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

    MedlinePLUS

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

  11. Brain Tumor Diagnosis

    MedlinePLUS

    ... Financials Board of Directors Scientific Advisory Council & Reviewers Leadership News Careers Brain Tumor Information Brain Anatomy Brain Tumor Symptoms Diagnosis Types of Tumors Tumor Grade Risk Factors Brain Tumor ...

  12. Diagnosis of Periodontal Diseases

    Microsoft Academic Search

    R. R. Ranney

    1991-01-01

    This paper reviews current (Fall, 1990) information related to the diagnosis of periodontal diseases. As background, principles of diagnostic decision-making and conceptual shifts during the 1970's and 1980's are reviewed in brief. \\

  13. Food Allergy Diagnosis

    MedlinePLUS

    ... JavaScript on. Read more information on enabling JavaScript. Food Allergy Skip Content Marketing Share this: Main Content ... diagnosis of food allergy. back to top Oral food challenge Caution Because oral food challenges can cause ...

  14. Reactive Arthritis Diagnosis

    MedlinePLUS

    Reactive Arthritis (ReA): Quick Links Overview >>> Symptoms >>> Diagnosis >>> Treatment >>> Medication >>> Doctor Q&A From Spondylitis Plus >>> REACTIVE ARTHRITIS Overview Because there is no specific laboratory test ...

  15. Porphyrins and Porphyria Diagnosis

    MedlinePLUS

    ... Sale You are here Home Testing for Porphyria Porphyrins & Porphyria diagnosis The porphyrias are caused by deficiencies ... when the conditions are active. These intermediates include porphyrin precursors (delta-aminolevulinic acid and porphobilinogen) and porphyrins. ...

  16. 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 ...

  17. 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)

  18. Diagnosis of urticaria.

    PubMed

    Schoepke, Nicole; Doumoulakis, Georgios; Maurer, Marcus

    2013-05-01

    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

  19. Familial cystinuria in Ioannina District (Greece) diagnosis and treatment

    Microsoft Academic Search

    G. Kallistratos; C. Dimopoulos; V. Kalfakakou-Vadalouka; A. Evangelou; D. Stockidis; P. Vezyraki; C. Charalambopoulos; I. Mita

    1983-01-01

    The “Urocystin Test” has been used as a screening procedure for the diagnosis of the incidence of cystinuria in Ioannina District (Northwest Greece). From the 210 investigated urine samples, eight were positive and four of them were also L-cystine stone formers. All positive cases belong to two cystinuric families. The pedigree in village “Kato-Lapsista” is a genetic type of a

  20. Familial Evaluation for Diagnosis of Arrhythmogenic Right Ventricular Dysplasia

    Microsoft Academic Search

    Brian T. Palmisano; Jeffrey N. Rottman; Quinn S. Wells; Thomas G. DiSalvo; Charles C. Hong

    2011-01-01

    Most sudden cardiac deaths in young athletes are caused by previously undetected inherited cardiac diseases. Here, we report a case of a young male athlete in whom a presumptive diagnosis of hypertrophic cardiomyopathy (HCM) was made following a near sudden cardiac death. Although his imaging studies initially suggested HCM, a detailed clinical and genetic evaluation of the patient and his

  1. Molecular Diagnosis of Deafness: Impact of Gene Identification

    Microsoft Academic Search

    Shin-ichi Usami; Eiko Koda; Koji Tsukamoto; Akihiro Otsuka; Isamu Yuge; Kenji Asamura; Satoko Abe; Jiro Akita; Atsushi Namba

    2002-01-01

    Recent progress in identifying genes responsible for hearing loss enables the ENT clinician to apply molecular diagnosis by genetic testing. This article focuses on three genes, which are prevalent and therefore commonly encountered in the clinic. GJB2 (connexin 26) is currently recognized as the most prevalent gene responsible for congenital hearing loss in many countries. A series of reports revealed

  2. 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.

  3. SCN1A Genetic Test for Dravet Syndrome (Severe Myoclonic Epilepsy of Infancy and its Clinical Subtypes) for use in the Diagnosis, Prognosis, Treatment and Management of Dravet Syndrome

    PubMed Central

    Stenhouse, Susan A.R.; Ellis, Rachael; Zuberi, Sameer

    2013-01-01

    Classic Dravet syndrome is also termed severe myoclonic epilepsy of infancy (SMEI). There are subtle phenotypic variants of Dravet which may have all the features of the syndrome except one, such as without myoclonic seizures, onset in the second year or without generalized spike and wave on EEG. These have been termed borderline variants of SMEI. Rather than ascribing multiple different names to marginally different phenotypes, the term Dravet syndrome is now preferred to describe the group of severe infantile onset epilepsies (OMIM #607208, #182389, #604403) associated with mutations in SCN1A (OMIM *182389). SCN1A-related seizure disorders can be inherited in an autosomal dominant manner but most are due to de novo mutations. SCN1A testing can be done through bi-directional DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) for: 1) individuals with electroclinical phenotype of Dravet Syndrome or clinical sub-types – several seizure types in one individual with onset in infancy, refractory to medication and with generalised spike and wave on EEG, or 2) infants less than 1 year old with 2 or more prolonged hemiclonic febrile seizures in early infancy. Disclaimer: This summary is based on a UK Genetic Testing Network (UKGTN) approved Gene Dossier application. PMID:23653348

  4. Establishment of the first WHO international genetic reference panel for Prader Willi and Angelman syndromes

    Microsoft Academic Search

    Jennifer Boyle; Malcolm Hawkins; David E Barton; Karen Meaney; Miriam Guitart; Anna O'Grady; Simon Tobi; Simon C Ramsden; Rob Elles; Elaine Gray; Paul Metcalfe; J Ross Hawkins

    2011-01-01

    Prader Willi and Angelman syndromes are clinically distinct genetic disorders both mapping to chromosome region 15q11-q13, which are caused by a loss of function of paternally or maternally inherited genes in the region, respectively. With clinical diagnosis often being difficult, particularly in infancy, confirmatory genetic diagnosis is essential to enable clinical intervention. However, the latter is challenged by the complex

  5. Diagnosis and management of primary ciliary dyskinesia.

    PubMed

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

    2014-09-01

    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

  6. 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

  7. 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

  8. Diagnosis of fanconi anemia by diepoxybutane analysis.

    PubMed

    Auerbach, Arleen D

    2015-01-01

    Fanconi anemia (FA) is a genetically and phenotypically heterogeneous disorder characterized by congenital malformations, progressive bone marrow failure, and predisposition to cancer, particularly hematological malignancies and solid tumors of the head and neck. The main role of FA proteins is in the repair of DNA interstrand crosslinks (ICLs). FA results from pathogenic variants in at least sixteen distinct genes, causing genomic instability. Although the highly variable phenotype makes accurate diagnosis on the basis of clinical manifestations difficult in some patients, diagnosis based on a profound sensitivity to DNA-crosslinking agents can be used to identify the pre-anemia patient as well as patients with aplastic anemia or leukemia who may or may not have the physical stigmata associated with the syndrome. Diepoxybutane (DEB) analysis is the preferred test for FA because other agents have higher rates of false-positive and false-negative results. © 2015 by John Wiley & Sons, Inc. PMID:25827349

  9. Genetic counseling 

    E-print Network

    Stough, Laura

    2014-01-01

    be at increased risk for complications or disability, as well as women over 35 who are pregnant. Couples who already have a child with a genetic disability or who give birth to infants diagnosed with a genetic dis- ease by routine newborn screening may also seek...). Genetic counselors usually work as part of a health- care team, providing information and support to families who have members with birth defects or genetic disor- ders and to families who may be at risk for a variety of inherited conditions (National...

  10. 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

  11. 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.

  12. Genetic and epigenetic alterations in differentiated thyroid carcinoma

    PubMed Central

    Brehar, AC; Brehar, FM; Bulgar, AC; Dumitrache, C

    2013-01-01

    Abstract Differentiated thyroid carcinoma (DTC) has a favorable prognosis, but it is important to identify those patients who have a high risk of progressive disease and DTC-related death at the time of diagnosis. Analyzing genetic and epigenetic alterations in thyroid cancer may play a role in tumor diagnosis, prognostic and therapeutic strategies. PMID:24868250

  13. 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

  14. Birth Defects Diagnosis

    MedlinePLUS

    ... Health Family Health History and Genetics Healthy Pregnancy Planning for Pregnancy A-Z Index of Birth Defects, Blood Disorders & Disabilities Information For... Media Policy Makers Language: English Español (Spanish) File Formats Help: How do ...

  15. Genetically modified.

    PubMed

    Cheek, Dennis J; Brazeau, Dan

    2015-05-01

    SINCE THE 1990s, and certainly since the completion of the Human Genome Project in 2003, the need for nurses to understand genetic information has become increasingly evident. Knowledge of genetics, genomics, pharmacogenetics and pharmacogenomics, the study of heredity, gene function and how medication targets genes, continues to increase and is important in the nursing care of patients. PMID:26014775

  16. 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.

  17. genetic disease

    Microsoft Academic Search

    Gerhard Nahler

    \\u000a Disease linked to a genetic defect such as a mutated gene; there are about 4,000 to 5,000 genetic diseases known to medical\\u000a science such as cystic fibrosis, Down syndrome, sickle cell anemia, haemophilia, Gilles de la Tourette syndrome or Fabry’s\\u000a disease; ? see also gene therapy, orphan diseases.

  18. Social genetics

    Microsoft Academic Search

    J. P. Scott

    1977-01-01

    Most behavior is expressed within social systems, and the genetic analysis of its variance therefore presents theoretical and technical problems that have been sidestepped in most previous research. The dog presents obvious advantages for studying behavioral interactions between genotypes. Two sets of data are summarized that indicate that the magnitude of genetic differences is related to the differentiation of social

  19. Diagnosis of mitochondrial myopathies.

    PubMed

    Milone, Margherita; Wong, Lee-Jun

    2013-01-01

    Mitochondria are ubiquitous organelles and play crucial roles in vital functions, most importantly, the oxidative phosphorylation and energy metabolism. Therefore, mitochondrial dysfunction can affect multiple tissues, with muscle and nerve preferentially affected. Mitochondrial myopathy is a common clinical phenotype, which is characterized by early fatigue and/or fixed muscle weakness; rhabdomyolysis can seldom occur. Muscle biopsy often identifies signs of diseased mitochondria by morphological studies, while biochemical analysis may identify respiratory chain deficiencies. The clinical, morphological and biochemical data guide molecular analysis. Being the mitochondrial function under the control of both mitochondrial DNA and nuclear DNA, the search for mitochondrial DNA mutations and mitochondrial DNA quantitation, may not be sufficient for the molecular diagnosis of mitochondrial myopathies. Approximately 1500 nuclear genes can affect mitochondrial structure and function and the targeting of such genes may be necessary to reach the diagnosis. The identification of causative molecular defects in nuclear or mitochondrial genome leads to the definite diagnosis of mitochondrial myopathy. PMID:23911206

  20. The Diagnosis of MS.

    PubMed

    Mallam, E; Scolding, N

    2009-04-01

    Diagnosing multiple sclerosis (MS) is not always straightforward. The very nature of this disease means that it can manifest in multiple varied clinical presentations. Diagnosis is further confounded by the lack of a single diagnostic test and a gargantuan list of differential diagnoses. Traditionally the diagnosis of MS is a clinical one: with the history and/or examination revealing the separation in time and space of neurological episodes. In some cases, however, a diagnosis of "possible MS" might have to be made, for example, when the patient presents after a single event. Paraclinical investigations and diagnostic criteria may be of help in these situations. It is recommended that any diagnostic uncertainty is discussed openly with patients. PMID:19413922

  1. Diagnosis of hepatocellular carcinoma

    PubMed Central

    Di Bisceglie, Adrian M.

    2005-01-01

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

  2. Syncope: diagnosis and management.

    PubMed

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

    2015-02-01

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

  3. Human prenatal diagnosis

    SciTech Connect

    Filkins, K.; Russo, R.J.

    1985-01-01

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

  4. [Diagnosis of olfactory disorders].

    PubMed

    Schriever, V A; Abolmaali, N; Welge-Lüssen, A

    2014-12-01

    Alongside a structured case history, the measurement of olfactory function and diagnosis of olfactory dysfunction is of great clinical importance. Validated and established methods have been developed to this aim. The "Sniffin' Sticks" test battery is an easy-to-use tool for assessing olfactory function. Recording of olfactory event-related potentials is a more objective approach, which is particularly important in medicolegal cases. Imaging techniques such as MRI and CT provide additional information in the diagnosis of olfactory disorders. The latter techniques enable the anatomical structures of the skull and brain with the areas relevant to olfactory function to be evaluated. PMID:25465077

  5. Case for diagnosis.

    PubMed

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

    2013-01-01

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

  6. Case for diagnosis*

    PubMed Central

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

    2013-01-01

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

  7. Lasers In Dental Diagnosis

    NASA Astrophysics Data System (ADS)

    Everse, K. E.; Sinor, T. W.; Menzel, E. R.

    1987-01-01

    We have investigated the potential of lasers for real time in situ dental diagnosis via transillumination of teeth and gums and via fluorescence. Not surprisingly, absorption and/or scattering of light by teeth was found to be insensitive to light color. However, monochromatic transillumination revealed detail better than white light. Transillumination of gums was best performed with orange-red light because of tissue absorption. Illumination of oral structures by 488 nm Ar-laser light was effective in revealing diagnosis detail by fluorescence. Incipient caries and fine tooth fracture lines that are generally not revealed by radiography were observable by laser.

  8. 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

  9. Eugenic selection benefits embryos.

    PubMed

    Walker, Mark

    2014-06-01

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

  10. 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.

  11. Lymphangioleiomyomatosis: differential diagnosis and optimal management

    PubMed Central

    Xu, Kai-Feng; Lo, Bee Hong

    2014-01-01

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

  12. 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

  13. Genetic Counseling Training

    MedlinePLUS

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

  14. 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 ...

  15. Genetic Terminology

    PubMed Central

    Elston, Robert; Satagopan, Jaya; Sun, Shuying

    2015-01-01

    Summary Common terms used in genetics with multiple meanings are explained and the terminology used in subsequent chapters is defined. Statistical Human Genetics has existed as a discipline for over a century, and during that time the meanings of many of the terms used have evolved, largely driven by molecular discoveries, to the point that molecular and statistical geneticists often have difficulty understanding each other. It is therefore imperative, now that so much of molecular genetics is becoming an in silico and statistical science, that we have well-defined, common terminology. PMID:22307690

  16. Prenatal diagnosis: whose right?

    PubMed

    Heyd, D

    1995-10-01

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

  17. Avian influenza - diagnosis.

    PubMed

    Alexander, D J

    2008-01-01

    The diagnosis of avian influenza (AI) virus infections, even highly pathogenic AI (HPAI), represents a considerable challenge due to the lack of pathognomonic or specific clinical signs and their variation in different avian hosts plus the marked antigenic variation amongst influenza A viruses. Conventional laboratory techniques involve the isolation, identification and characterization (including virulence estimates) of the virus. While this has proven successful in the past and remains the method of choice, for at least the initial outbreak, the delays associated with conventional diagnosis are often considered unacceptable for the application of control measures, especially stamping out policies, and there is an overwhelming demand for rapid results. More and more, molecular biological techniques are being used and in particular reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR technologies are being employed for rapid diagnosis. In this paper, clinical signs, the molecular basis for virulence of AI viruses, international definitions, conventional diagnosis and the use of molecular techniques are reviewed and discussed. PMID:18201322

  18. Diagnosis of hepatocellular carcinoma

    PubMed Central

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

    2009-01-01

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

  19. Application of Strength Diagnosis.

    ERIC Educational Resources Information Center

    Newton, Robert U.; Dugan, Eric

    2002-01-01

    Discusses the various strength qualities (maximum strength, high- and low-load speed strength, reactive strength, rate of force development, and skill performance), noting why a training program design based on strength diagnosis can lead to greater efficacy and better performance gains for the athlete. Examples of tests used to assess strength…

  20. 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…

  1. 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....

  2. Anomaly detection for diagnosis

    Microsoft Academic Search

    Roy A. Maxion

    1990-01-01

    The author presents a method for detecting anomalous events in communication networks and other similarly characterized environments in which performance anomalies are indicative of failure. The methodology, based on automatically learning the difference between normal and abnormal behavior, has been implemented as part of an automated diagnosis system from which performance results are drawn and presented. The dynamic nature of

  3. Achieving Diagnosis by Consensus

    Microsoft Academic Search

    Bridget Kane; Saturnino Luz

    2009-01-01

    Received: date \\/ Accepted: date Abstract This paper provides an analysis of the collaborative work con- ducted at a multidisciplinary medical team meeting, where a patient's defini- tive diagnosis is agreed, by consensus. The features that distinguish this pro- cess of diagnostic work by consensus are examined in depth. The current use of technology to support this collaborative activity is

  4. Diagnosis of celiac sprue

    Microsoft Academic Search

    Richard J. Farrell; Ciaran P. Kelly

    2001-01-01

    Celiac sprue is a common lifelong disorder affecting 0.3–1% of the Western world and causing considerable ill health and increased mortality, particularly from lymphoma and other malignancies. Although high prevalence rates have been reported in Western Europe, celiac sprue remains a rare diagnosis in North America. Whether celiac sprue is truly rare among North Americans or is simply underdiagnosed is

  5. Dry eye diagnosis

    Microsoft Academic Search

    Khanal Santosh; Alan Tomlinson; Angus McFadyen; Charles J. M. Diaper; Kanna Ramaesh

    2008-01-01

    The aim of this study was to determine the most effective objective tests, applied singly or in combination in the diagnosis of dry eye disease. Two groups of subjects—41 with dry eye and 32 with no ocular surface disease—had symptoms, tear film quality, evaporation, tear turnover rate (TTR), volume and osmolarity, and meibomian gland dropout score assessed.

  6. Diagnosis of toxoplasmosis and typing of Toxoplasma gondii.

    PubMed

    Liu, Quan; Wang, Ze-Dong; Huang, Si-Yang; Zhu, Xing-Quan

    2015-01-01

    Toxoplasmosis, caused by the obligate intracellular protozoan Toxoplasma gondii, is an important zoonosis with medical and veterinary importance worldwide. The disease is mainly contracted by ingesting undercooked or raw meat containing viable tissue cysts, or by ingesting food or water contaminated with oocysts. The diagnosis and genetic characterization of T. gondii infection is crucial for the surveillance, prevention and control of toxoplasmosis. Traditional approaches for the diagnosis of toxoplasmosis include etiological, immunological and imaging techniques. Diagnosis of toxoplasmosis has been improved by the emergence of molecular technologies to amplify parasite nucleic acids. Among these, polymerase chain reaction (PCR)-based molecular techniques have been useful for the genetic characterization of T. gondii. Serotyping methods based on polymorphic polypeptides have the potential to become the choice for typing T. gondii in humans and animals. In this review, we summarize conventional non-DNA-based diagnostic methods, and the DNA-based molecular techniques for the diagnosis and genetic characterization of T. gondii. These techniques have provided foundations for further development of more effective and accurate detection of T. gondii infection. These advances will contribute to an improved understanding of the epidemiology, prevention and control of toxoplasmosis. PMID:26017718

  7. Transposon mutagenesis disentangles osteosarcoma genetic drivers.

    PubMed

    Jones, Kevin B

    2015-05-27

    The genetic drivers of osteosarcoma have been difficult to identify because of the genomic complexity consistently encountered in cancer cells at diagnosis. A new study uses Sleeping Beauty transposon mutagenesis to drive osteosarcomagenesis in the mouse and identify likely drivers of the disease in humans. PMID:26018893

  8. Hereditary thyroid cancer syndromes and genetic testing.

    PubMed

    Rowland, Kathryn J; Moley, Jeffrey F

    2015-01-01

    This review focuses on both hereditary medullary thyroid cancer (MTC) and hereditary nonmedullary thyroid cancer (NMTC) and discusses the genetics, clinical diagnosis and evaluation, and surgical approach to treatment of these malignancies. Areas of innovation as well as areas of debate are highlighted and management recommendations are made. PMID:25351655

  9. [Clinical and Laboratory Diagnosis of Central Nervous System Infections].

    PubMed

    Morita, Akihiko

    2015-07-01

    Central nervous system (CNS) infections, including acute encephalitis, bacterial meningitis, tuberculous meningitis, and fungal meningitis, represent a potentially life-threatening neurological emergency. An etiological diagnosis of CNS infection is made a definite diagnosis based on the identification of pathogenic agents in the CNS using cerebrospinal fluid (CSF) smears or cultures, the identification of pathogenic antigens in CSF, the identification of pathogenic products in brain tissues or CSF with polymerase chain reaction (PCR), or the identification of specific antibody responses in CSF. Since time is required to obtain results from these laboratory tests, initial empirical treatments for the suspected CNS infection are required. The optimal specimen sampling and delivery is an essential requirement to reach the definite diagnosis. Nucleic acid amplification tests, such as PCR assays, show high sensitivity and specificity in detecting pathogens from CSF. In Japan, most genetic tests for pathogenic agents are performed as part of academic research. The number of commercially available genetic tests is limited. Moreover, no genetic tests for pathogenic agents in the CSF are covered by the national health insurance system in Japan. To manage the continuity of genetic tests, this inefficient system should be improved. PMID:26160808

  10. Genetic Testing

    MedlinePLUS

    ... on to their children Screening embryos for disease Testing for genetic diseases in adults before they cause ... provide information about the pros and cons of testing. NIH: National Human Genome Research Institute

  11. 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…

  12. Genetic Algorithms

    Microsoft Academic Search

    Enrique Alba; Francisco Chicano

    In this chapter we describe the basics of Genetic Algorithms and how they can be used to train Artificial Neural Networks.\\u000a Supervised training of Multilayer Perceptrons for classification problems is considered. We also explain how the Genetic Algorithm\\u000a can be hybridized with other algorithms and present two hybrids between it and two classical algorithms for the neural network\\u000a training: Backpropagation

  13. Genetic counseling

    E-print Network

    Stough, Laura

    2014-01-01

    syndrome or spina bifida, while postnatal testing may reveal phenylke- tonuria or hypothyroidism. Most disorders occur when one or both of the parents pass on their genes. Couples who are carriers may choose to have their DNA tested before conception... 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...

  14. Genetics of obesity and overgrowth syndromes.

    PubMed

    Sabin, Matthew A; Werther, George A; Kiess, Wieland

    2011-02-01

    Childhood overweight and obesity is highly prevalent within society. In the majority of individuals, weight gain is the result of exposure to an 'obesogenic' environment, superimposed on a background of genetic susceptibility brought about by evolutionary adaptation. These individuals tend to be tall in childhood with a normal final adult height, as opposed to those who have an underlying monogenic cause where short stature is more common (although not universal). Identifying genetic causes of weight gain, or tall stature and overgrowth, within this setting can be extremely problematic and yet it is imperative that clinicians remain alert, as identification of a genetic diagnosis has major implications for the individual, family and potential offspring. Alongside this, the recognition of new genetic mutations in this area is furthering our knowledge on the important mechanisms that regulate childhood growth and body composition. This review describes the genetic syndromes associated with obesity and overgrowth. PMID:21396586

  15. 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

  16. Pitfalls and pearls in the diagnosis of monilethrix.

    PubMed

    Leitner, Christina; Cheung, Seautak; de Berker, David

    2013-01-01

    A 4-year-old girl presented with sparse, brittle hair on her entire scalp and keratosis pilaris on the nape of her neck. Subtle microscopic and macroscopic diagnostic features presented a challenge for physicians. Only repeated, optimized light microscopy revealed the diagnosis of monilethrix, a rare genetic hair shaft disorder with a variable phenotypic expression and inheritance pattern. We provide a short overview of methods that maximize the diagnostic yield in a clinical setting and of light microscopy to reach a rapid and accurate diagnosis in difficult cases. We conclude with essential learning points, including a link to assistance with hair microscopy from a tertiary center. PMID:23834295

  17. Positive muscle phenomena--diagnosis, pathogenesis and associated disorders.

    PubMed

    Kortman, Hans G; Veldink, Jan H; Drost, Gea

    2012-02-01

    Positive muscle phenomena arise owing to various forms of spontaneous muscle hyperactivity originating in motor neurons or in the muscle itself. Although they are common in a wide range of neurological and non-neurological diseases, clinical and scientific data on these phenomena are limited, and their presence is sometimes overlooked. This gap in our knowledge hampers effective diagnosis and treatment. In this article, we review the clinical characteristics and approach to diagnosis of the various positive muscle phenomena, and discuss their genetic underpinnings and pathophysiological mechanisms. Finally, we outline an algorithm to discriminate between the different positive muscle phenomena. PMID:22270020

  18. [Tongue diagnosis support system].

    PubMed

    Ikeda, Naoya; Uozumi, Takashi

    2005-05-01

    Tongue diagnosis is one of the most important diagnostic methods in Oriental Medical Science (OMS). This diagnosis is painless and non-invasive method. However, it is not easy to cultivate skillful doctors. As one of the reasons, definition of tongue color is rather subjective and sensuous measure and color isn't related to quantitative physical value. It is, therefore, necessary to associate tongue color with physical numerical value. There are two problems to overcome the issue. 1) It is necessary for diagnosis to extract a region for diagnosis from entire picture because a tongue picture consists of two regions, a tongue and a background. 2) Associate tongue color with physical numerical value. For extracting tongue region, we used Progressive LiveWire method that is an Active Contour Model. And, for associating tongue color with physical measurement, we propose a hierarchical method. We use static rule and support vector machine for clustering colors. The performance of developed system is improved compared with an early developed one. In addition, the developed system did not make a critical incorrect discernment that causes incorrect choice about inspection in the layer of rule base. In this research average color appraisal is done from the region of 37 points. But, color judgment in the literature with the judgment by the eye of the human, has always done average judgment with not to limit, there is also a possibility some weight attaching being done. Therefore, from either one enabling the mass data and the comparison with the group of specialists is necessary as an appraisal. PMID:15960161

  19. Diagnosis of Prostate Cancer

    Microsoft Academic Search

    Jehonathan H. Pinthus; Dalibor Pacik; Jacob Ramon

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

  20. Deformation Zone Diagnosis

    NSDL National Science Digital Library

    COMET

    2007-11-05

    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".

  1. Population structure of the Chenchu and other south Indian tribal groups: relationships between genetic, anthropometric, dermatoglyphic, geographic, and linguistic distances.

    PubMed

    Sirajuddin, S M; Duggirala, R; Crawford, M H

    1994-10-01

    We describe the genetic structure and interrelationships of nine south Indian tribal groups (seven from Andhra Pradesh and two from the adjoining states of Tamil Nadu and Kerala) using seven polymorphic loci (ABO, MN, RH, PGM, ACP, PGD, and LDH). R matrix analysis indicates that the Andhra Pradesh tribes are clustered and that the Kadar and Irula are genetically isolated from them. This dispersion of populations has been explained by the combination of relatively high frequencies of the alleles RH D and MN M in the Kadar and the relatively high proportions of the allele PGM*2 in the Irula. The Mahaboobnagar Chenchu subgroup is isolated from other Telugu-speaking groups because of high frequencies of the PGM*1 and ACP*A alleles. The regression of mean per locus heterozygosity (H) on distance from the gene frequency centroid (rii) reveals considerable levels of external gene flow among the Lambadi, the Yerukula, and the two Chenchu subgroups and more homogeneity in the Kolam, Koya, Yanadi, Irula, and Kadar. Mantel statistics were used to assess the relative effects of nonbiological processes (i.e., language and geography) on the morphological and genetic patterns of these subdivided populations. The significance of correlations was determined between different data sets (genetic, dermatoglyphic, anthropometric, geographic, and linguistic) at three levels involving nine, six, and five populations. Although multiple correlation analysis reveals significant combined effects of geography and language on genetics, anthropometrics, and dermatoglyphics, highly significant partial correlations suggest strong effects of geography on both anthropometry and genetics. Our analysis indicates that geographic factors have an overwhelming effect on the genetic differentiation of the south Indian tribal groups. PMID:8001914

  2. [Diagnosis of maternofetal infections].

    PubMed

    Vauloup-Fellous, Christelle; Bouthry, Elise

    2015-06-01

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

  3. Laboratory diagnosis of SARS.

    PubMed Central

    Bermingham, A; Heinen, P; Iturriza-Gómara, M; Gray, J; Appleton, H; Zambon, M C

    2004-01-01

    The emergence of new viral infections of man requires the development of robust diagnostic tests that can be applied in the differential diagnosis of acute illness, or to determine past exposure, so as to establish the true burden of disease. Since the recognition in April 2003 of the severe acute respiratory syndrome coronavirus (SARS-CoV) as the causative agent of severe acute respiratory syndrome (SARS), enormous efforts have been applied to develop molecular and serological tests for SARS which can assist rapid detection of cases, accurate diagnosis of illness and the application of control measures. International progress in the laboratory diagnosis of SARS-CoV infection during acute illness has led to internationally agreed World Health Organization criteria for the confirmation of SARS. Developments in the dissection of the human immune response to SARS indicate that serological tests on convalescent sera are essential to confirm SARS infection, given the sub-optimal predictive value of molecular detection tests performed during acute SARS illness. PMID:15306394

  4. Diagnosis of CIDP.

    PubMed

    Latov, Norman

    2002-12-24

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease that targets the myelin sheaths of peripheral nerves. In clinical practice the diagnosis is often difficult to make because of the clinical heterogeneity of the disease, its multifocality and predilection for proximal nerve segments, and the limitations of our electrophysiologic and pathologic techniques. Although there are rather stringent research criteria for selecting patients to clinical trials, there are no generally agreed-on clinical diagnostic criteria for CIDP, and application of the research criteria to routine clinical practice would miss the diagnosis in a majority of patients. Because of this uncertainty, the prevalence of CIDP is greatly underestimated, and patients are often left untreated despite progression of their disease. However, given what is known about the clinical presentation and pathophysiology of CIDP, patients with neuropathy of otherwise unknown etiology are more likely to have CIDP than idiopathic axonal neuropathy, and warrant a trial of therapy if they have nerve conduction velocities below the lower limits of normal, prolongation of F-waves beyond the normal range, or presence of conduction block or temporal dispersion. A favorable response to therapy, consisting of stabilization or improvement of the neuropathy, would confirm the diagnosis. PMID:12499464

  5. Genetic and morphological differentiation in Tephritis bardanae (Diptera: Tephritidae): evidence for host-race formation.

    PubMed

    Diegisser, T; Johannesen, J; Lehr, C; Seitz, A

    2004-01-01

    The fruit fly Tephritis bardanae infests flower heads of two burdock hosts, Arctium tomentosum and A. minus. Observations suggest host-associated mating and behavioural differences at oviposition indicating host-race status. Previously, flies from each host plant were found to differ slightly in allozyme allele frequencies, but these differences could as well be explained by geographical separation of host plants. In the present study, we explicitly test whether genetic and morphological variance among T. bardanae are explained best by host-plant association or by geographical location, and if this pattern is stable over a 10-year period. Populations of A. tomentosum flies differed significantly from those of A. minus flies in (i) allozyme allele frequencies at the loci Pep-A and Pgd, (ii) mtDNA haplotype frequencies and (iii) wing size. In contrast, geographical location had no significant influence on the variance estimates. While it remains uncertain whether morphometric differentiation reflects genotypic variability or phenotypic plasticity, allozyme and mtDNA differentiation is genetically determined. This provides strong evidence for host-race formation in T. bardanae. However, the levels of differentiation are relatively low indicating that the system is in an early stage of divergence. This might be due to a lack of time (i.e. the host shift occurred recently) or due to relatively high gene flow preventing much differentiation at loci not experiencing selection. PMID:15000651

  6. Actuarial considerations on genetic testing.

    PubMed

    Le Grys, D J

    1997-08-29

    In the UK the majority of life insurers employ relatively liberal underwriting standards so that people can easily gain access to life assurance cover. Up to 95% of applicants are accepted at standard terms. If genetic testing becomes widespread then the buying habits of the public may change. Proportionately more people with a predisposition to major types of disease may take life assurance cover while people with no predisposition may take proportionately less. A model is used to show the possible effect. However, the time-scales are long and the mortality of assured people is steadily improving. The change in buying habits may result in the rate of improvement slowing down. In the whole population, the improvement in mortality is likely to continue and could improve faster if widespread genetic testing results in earlier diagnosis and treatment. Life insurers would not call for genetic tests and need not see the results of previous tests except for very large sums assured. In the UK, life insurers are unlikely to change their underwriting standards, and are extremely unlikely to bring in basic premium rating systems that give discounts on the premium or penalty points according to peoples genetic profile. The implications of widespread genetic testing on medical insurance and some health insurance covers may be more extreme. PMID:9304671

  7. Actuarial considerations on genetic testing.

    PubMed Central

    Le Grys, D J

    1997-01-01

    In the UK the majority of life insurers employ relatively liberal underwriting standards so that people can easily gain access to life assurance cover. Up to 95% of applicants are accepted at standard terms. If genetic testing becomes widespread then the buying habits of the public may change. Proportionately more people with a predisposition to major types of disease may take life assurance cover while people with no predisposition may take proportionately less. A model is used to show the possible effect. However, the time-scales are long and the mortality of assured people is steadily improving. The change in buying habits may result in the rate of improvement slowing down. In the whole population, the improvement in mortality is likely to continue and could improve faster if widespread genetic testing results in earlier diagnosis and treatment. Life insurers would not call for genetic tests and need not see the results of previous tests except for very large sums assured. In the UK, life insurers are unlikely to change their underwriting standards, and are extremely unlikely to bring in basic premium rating systems that give discounts on the premium or penalty points according to peoples genetic profile. The implications of widespread genetic testing on medical insurance and some health insurance covers may be more extreme. PMID:9304671

  8. Genetics Home Reference: Hypochondroplasia

    MedlinePLUS

    ... for hypochondroplasia? HCH Hypochondrodysplasia For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes ...

  9. Genetics Home Reference: Hypercholesterolemia

    MedlinePLUS

    ... for hypercholesterolemia? Elevated cholesterol For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes ...

  10. Genetics of hearing and deafness.

    PubMed

    Angeli, Simon; Lin, Xi; Liu, Xue Zhong

    2012-11-01

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

  11. 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

  12. Genetics of SCID

    PubMed Central

    2010-01-01

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

  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. Genetic Testing for Pheochromocytoma

    PubMed Central

    Karasek, David; Frysak, Zdenek; Pacak, Karel

    2011-01-01

    Pheochromocytomas and paragangliomas (PHEOs/PGLs) are rare, usually sporadic, catecholamine-producing tumors. However, about 30% of these tumors have been identified of inherited origin. Up to date, nine genes have been confirmed to participate in PHEOs/PGLs tumorigenesis. Germline mutations used to be found in 100% of syndromic cases and in about 90% of patients with positive familial history. In non-syndromic patients with apparently sporadic tumors the frequency of genetic mutations has been recorded up to 27%. Nowadays, genetic testing is recommended for all patients with PHEOs/PGLs. Patients with syndromic lesions and/or positive family history should be tested for appertaining gene. Latest discoveries have shown that the proper order of tested genes in non-syndromic, non-familial cases could be based on histological evaluation, localization and biochemical phenotype of PHEOs/PGLs – the “rule of three”. Identification of gene mutation may lead to early diagnosis, treatment, regular surveillance and better prognosis for patients and their relatives. PMID:20938758

  15. [Genetics of congenital deafness].

    PubMed

    Faundes, Víctor; Pardo, Rosa Andrea; Castillo Taucher, Silvia

    2012-10-20

    Congenital deafness is defined as the hearing loss which is present at birth and, consequently, before speech development. It is the most prevalent sensor neural disorder in developed countries, and its incidence is estimated between 1-3 children per 1,000 newborns, of which more than 50% are attributable to genetics causes. Deafness can be classified as syndromic or non-syndromic. In the first case, it is associated with outer ear malformations and/or systemic findings. More than 400 syndromes accompanied of deafness have been described, which represent about 30% of cases of congenital hearing loss. The remaining percentage corresponds to non-syndromic cases: 75-85% are autosomal recessive, 15-24% are autosomal dominant, and 1-2% are X-linked. The evaluation of a child with deafness requires a multidisciplinary collaboration among specialists, who must coordinate themselves and give information to the affected family. The aims of establishing a diagnosis are to predict other manifestations that may suggest some syndrome and to anticipate their management, as well as to perform genetic counseling to parents and affected individuals. PMID:22538062

  16. Genetic Testing in Presymptomatic Diagnosis of Multiple Endocrine Neoplasia

    Microsoft Academic Search

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

    1997-01-01

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

  17. 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

  18. 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

  19. [Hereditary spherocytosis: Review. Part I. History, demographics, pathogenesis, and diagnosis].

    PubMed

    Donato, Hugo; Crisp, Renée Leonor; Rapetti, María Cristina; García, Eliana; Attie, Myriam

    2015-01-01

    Hereditary spherocytosis is the most frequent hereditary anemia excluding beta thalassemia in Argentina. Historical, demographic, genetic and pathogenic aspects of the disease are reviewed, and confirmatory laboratory tests are described. Special characteristics on the outcome of the disease in our population and prevalent protein deficiencies in our country are described. Emphasis is given on new available laboratory tests, which allow an earlier diagnosis using volume of blood samples significantly smaller than required for conventional tests. PMID:25622164

  20. MRI in the Diagnosis of Right Ventricular Dysplasia

    Microsoft Academic Search

    M. Midiri; M. Galia; T. V. Bartolotta

    ARVD is part of the group of cardiomyopathies characterised pathologically by fibrofatty replacement of the right ventricular\\u000a myocardium and clinically by right ventricular arrhythmias of the LBBB pattern. Pathogenesis, prevalence, and aetiology are\\u000a yet not fully known. The diagnosis of ARVD is based on the presence of structural, histological, electrocardiographic, and\\u000a genetic factors. Therapeutic options include antiarrhythmic medication, catheter ablation,

  1. 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

  2. Arsenicosis: diagnosis and treatment.

    PubMed

    Das, Nilay Kanti; Sengupta, Sujit Ranjan

    2008-01-01

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

  3. Case for diagnosis*

    PubMed Central

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

    2014-01-01

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

  4. Cancer Genetics Professionals

    Cancer.gov

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

  5. 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)

  6. 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.

  7. Hirsutism: diagnosis and treatment.

    PubMed

    Hohl, Alexandre; Ronsoni, Marcelo Fernando; Oliveira, Mônica de

    2014-03-01

    Hirsutism is defined as excessive terminal hair growth in androgen-dependent areas of the body in women, which grows in a typical male distribution pattern. Hirsutism is a common clinical problem in women, and the treatment depends on the cause. The condition is often associated with a loss of self-esteem. Hirsutism reflects the interaction between circulating androgen concentrations, local androgen concentrations, and the sensitivity of the hair follicle to androgens. Polycystic ovary syndrome and idiopathic hirsutism are the most common causes of the condition. A woman's history and, physical examination are particularly important in evaluating excess hair growth. The vast majority of women with hirsutism have the idiopathic variety, and the diagnosis is made by exclusion. Serum testosterone level>200 ng/dL is highly suggestive of adrenal or ovarian tumor. Treatment of hirsutism should be based on the degree of excess hair growth presented by the patient and in the pathophysiology of the disorder. Treatment includes lifestyle therapies, androgen suppression, peripheral androgen blockage, and cosmetic treatments. The current review discusses de?nition, pathogenesis, physiopathology, differential diagnosis, diagnostic strategies, and treatment. PMID:24830586

  8. DIAGNOSIS OF HISTOPLASMOSIS

    PubMed Central

    Guimarães, Allan Jefferson; Nosanchuk, Joshua D.; Zancopé-Oliveira, Rosely Maria

    2010-01-01

    Endemic mycoses can be challenging to diagnose and accurate interpretation of laboratory data is important to ensure the most appropriate treatment for the patients. Although the definitive diagnosis of histoplasmosis (HP), one of the most frequent endemic mycoses in the world, is achieved by direct diagnosis performed by micro and/or macroscopic observation of Histoplasma capsulatum (H. capsulatum), serologic evidence of this fungal infection is important since the isolation of the etiologic agents is time-consuming and insensitive. A variety of immunoassays have been used to detect specific antibodies to H. capsulatum. The most applied technique for antibody detection is immunodiffusion with sensitivity between 70 to 100 % and specificity of 100%, depending on the clinical form. The complement fixation (CF) test, a methodology extensively used on the past, is less specific (60 to 90%). Detecting fungal antigens by immunoassays is valuable in immunocompromised individuals where such assays achieve positive predictive values of 96–98%. Most current tests in diagnostic laboratories still utilize unpurified antigenic complexes from either whole fungal cells or their culture filtrates. Emphasis has shifted, however, to clinical immunoassays using highly purified and well-characterized antigens including recombinant antigens. In this paper, we review the current conventional diagnostic tools, such as complement fixation and immunodiffusion, outline the development of novel diagnostic reagents and methods, and discuss their relative merits and disadvantages to the immunodiagnostic of this mycosis. PMID:20445761

  9. A genetic algorithm tutorial

    Microsoft Academic Search

    DARRELL WHITLEY

    1993-01-01

    This tutorial covers the canonical genetic algorithm as well as more experimentalforms of genetic algorithms, including parallel island models and parallel cellular geneticalgorithms. The tutorial also illustrates genetic search by hyperplane sampling. Thetheoretical foundations of genetic algorithms are reviewed, include the schema theoremas well as recently developed exact models of the canonical genetic algorithm.Keywords: Genetic Algorithms, Search, Parallel Algorithms1 Introduction...

  10. Using Genetic Testing to Guide Therapeutic Decisions in Cardiomyopathy

    PubMed Central

    Lakdawala, Neal K

    2013-01-01

    Opinion statement Genetic analysis of human cardiomyopathy has rapidly transitioned from a strictly research endeavor to a diagnostic tool readily available to clinicians across the globe. In contemporary practice, genetic testing improves the efficiency of family evaluations and clarifies the etiology of ambiguous clinical presentations. The great promise of genetic diagnosis is to enable preventative therapies for individuals at high risk of future disease development, a strategy that is under active clinical investigation. However, in the present and future, careful interpretation of DNA sequence variation is critical, and can be ensured by referral to a specialized cardiovascular genetics clinic. PMID:23794152

  11. Genetic skeletal dysplasias in the Museum of Pathological Anatomy, Vienna.

    PubMed

    Beighton, P; Sujansky, E; Patzak, B; Portele, K A

    1993-11-01

    Skeletal material in the Museum of Pathological Anatomy, Vienna, has been appraised in order to modify existing descriptive designations and to establish diagnoses of specific genetic disorders. In this way osseous material relating to classical genetic syndromes has been identified and will be available for further study. Among the skeletons of adults in the museum, the following genetic conditions could be diagnosed: achondroplasia, Marfan syndrome, cleidocranial dysostosis, and diaphyseal aclasia. In adult sisters with dwarfism and a rickety bone disorder, the final diagnosis was uncertain. Infantile bone dysplasias, genetic conditions involving the skull, and malformation syndromes which are all represented in the museum are currently being analyzed. PMID:8279481

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

    PubMed Central

    Kendler, Kenneth S.; Hitzemann, Robert J.

    2012-01-01

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

  13. Genetic background of supernumerary teeth

    PubMed Central

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

    2015-01-01

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

  14. Genetic Counseling for Diabetes Mellitus

    PubMed Central

    Stein, Stephanie A.; Maloney, Kristin L.; Pollin, Toni I.

    2014-01-01

    Most diabetes is polygenic in etiology, with (type 1 diabetes, T1DM) or without (type 2 diabetes, T2DM) an autoimmune basis. Genetic counseling for diabetes generally focuses on providing empiric risk information based on family history and/or the effects of maternal hyperglycemia on pregnancy outcome. An estimated one to five percent of diabetes is monogenic in nature, e.g., maturity onset diabetes of the young (MODY), with molecular testing and etiology-based treatment available. However, recent studies show that most monogenic diabetes is misdiagnosed as T1DM or T2DM. While efforts are underway to increase the rate of diagnosis in the diabetes clinic, genetic counselors and clinical geneticists are in a prime position to identify monogenic cases through targeted questions during a family history combined with working in conjunction with diabetes professionals to diagnose and assure proper treatment and familial risk assessment for individuals with monogenic diabetes. PMID:25045596

  15. Genetically and medically susceptible workers.

    PubMed

    Mohr, S; Gochfeld, M; Pransky, G

    1999-01-01

    The likelihood of an individual becoming ill from a hazardous material or condition is strongly influenced by both their genetic makeup and their underlying state of health. Although the past decade has seen great advances in understanding human variation in health and genetic polymorphisms and in the diagnosis and treatment of disease, much less progress has been made in effectively using this information to protect worker health. Scientific evidence for increased susceptibility often is weak and rarely satisfies legal thresholds for sufficient risk to warrant exclusion from a particular job. When public safety is a major concern, many legally mandated exclusions are not well justified. Medical opinions about fitness to work should be based upon a systematic and credible analysis of the condition, its relationship to ability and risk for a particular job, and knowledge of possible accommodations. Conclusions should reflect the limitations of scientific knowledge and guidance from antidiscrimination legislation. PMID:10378978

  16. Molecular genetics of thyroid diseases.

    PubMed

    Ledent, C; Parma, J; Dumont, J; Vassart, G; Targovnik, H

    1994-01-01

    Over the past 20 years, recombinant deoxyribonucleic acid technology has led to the cloning of three major thyroid specific protein genes (thyroglobulin, thyroperoxidase and thyrotrophin receptor), which happen to be also the main thyroid autoantigens implicated in thyroid diseases. In this context, the impact that molecular genetics has had on the understanding of aetiopathogeny and diagnosis of thyroid diseases is summarized, with special emphasis on a recently discovered genetic mechanism responsible for toxic nodules. One fruitful outcome of the basic research on thyroid-specific gene expression has been the possibility of targeting the expression of a series of genes to the thyroid in transgenic mice. The result is the availability of mouse models mimicking human thyroid diseases such as destructive hypothyroidism, hyperactive thyroid adenomas and thyroid cancers exhibiting varying levels of differentiation. PMID:8124482

  17. Parkinson's Disease: From Genetics to Clinical Practice

    PubMed Central

    Clarimón, Jordi; Kulisevsky, Jaime

    2013-01-01

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

  18. Religious Traditions and Prenatal Genetic Counseling

    PubMed Central

    Anderson, Rebecca Rae

    2009-01-01

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

  19. Developments in Ocular Genetics: 2013 Annual Review

    PubMed Central

    Aboobakar, Inas F.; Allingham, R. Rand

    2014-01-01

    Purpose To highlight major advancements in ocular genetics from the year 2013. Design Literature review. Methods A literature search was conducted on PubMed to identify articles pertaining to genetic influences on human eye diseases. This review focuses on manuscripts published in print or online in the English language between January 1, 2013 and December 31, 2013. A total of 120 papers from 2013 were included in this review. Results Significant progress has been made in our understanding of the genetic basis of a broad group of ocular disorders, including glaucoma, age-related macular degeneration, cataract, diabetic retinopathy, keratoconus, Fuchs’ endothelial dystrophy, and refractive error. Conclusions The latest next-generation sequencing technologies have become extremely effective tools for identifying gene mutations associated with ocular disease. These technological advancements have also paved the way for utilization of genetic information in clinical practice, including disease diagnosis, prediction of treatment response and molecular interventions guided by gene-based knowledge. PMID:25097799

  20. Immunohistochemistry in bone marrow pathology: a useful adjunct for morphologic diagnosis

    Microsoft Academic Search

    Marcus Kremer; Leticia Quintanilla-Martínez; Jörg Nährig; Christoph von Schilling; Falko Fend

    2005-01-01

    Pathomorphological examination of trephine biopsies of the bone marrow (BM) represents a standard method for the diagnosis\\u000a and staging of hematologic neoplasms and other disorders involving the BM. The increasing knowledge about the genetic basis\\u000a and biology of hematologic neoplasms, as well as the recently proposed WHO classification system, provide the framework for\\u000a an accurate diagnosis. Although conventional morphology remains

  1. Genetics Home Reference: Achondroplasia

    MedlinePLUS

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

  2. Arsenicosis: Diagnosis and treatment Arsenicosis: Diagnosis and treatment

    Microsoft Academic Search

    Sujit Ranjan; Sengupta Nilay; Kanti Das; Sujit Ranjan Sengupta

    Diagnosis of arsenicosis relies on both clinical and laboratory criteria, but principally it can be diagnosed on the basis of its cutaneous manifestations. Cutaneous manifestations (melanosis, keratosis, and cutaneous cancers) are essential clues in the diagnosis, and trained dermatologists or arsenic experts are able to clinically conÞ rm a case even without laboratory backup. Although systemic manifestations are not considered

  3. [Diagnosis of acoustic neuroma].

    PubMed

    Messing, B; Lenarz, T; Steiner, H H

    1989-07-01

    Modern diagnostic procedures have enabled very early diagnosis of acoustic neuromas, making previously unattainable operative successes feasible. This change, which has taken place over the past decade, is demonstrated using data on 64 patients collected from 1970 to 1987. Over this period the case history shortened to a third, tumour size shrank to less than half and symptoms became more circumscribed and less severe. Operative results are impressive with regard to improvement or preservation of hearing and survival of the facial nerve. Technical diagnostic procedures can be reduced to a minimum of non-invasive methods. As very small intracanalicular neuromas can now be detected, there arises the question of the management strategy of choice, which would in selected cases include a period of watchful waiting. PMID:2761661

  4. 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.

  5. Rapid Diagnosis of Malaria

    PubMed Central

    Murray, Clinton K.; Bennett, Jason W.

    2009-01-01

    Malaria's global impact is expansive and includes the extremes of the healthcare system ranging from international travelers returning to nonendemic regions with tertiary referral medical care to residents in hyperendemic regions without access to medical care. Implementation of prompt and accurate diagnosis is needed to curb the expanding global impact of malaria associated with ever-increasing antimalarial drug resistance. Traditionally, malaria is diagnosed using clinical criteria and/or light microscopy even though both strategies are clearly inadequate in many healthcare settings. Hand held immunochromatographic rapid diagnostic tests (RDTs) have been recognized as an ideal alternative method for diagnosing malaria. Numerous malaria RDTs have been developed and are widely available; however, an assortment of issues related to these products have become apparent. This review provides a summary of RDT including effectiveness and strategies to select the ideal RDT in varying healthcare settings. PMID:19547702

  6. 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.

  7. Human genetics

    SciTech Connect

    Carlson, E.A.

    1984-01-01

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

  8. Genetic Engineering

    Microsoft Academic Search

    J. F. Kreuze; J. P. T. Valkonen; M. Ghislain

    Genetic transformation through direct gene transfer methods holds promise for introducing novel traits to sweetpotato in cases\\u000a where no solutions by conventional breeding are available. This may be if the trait is not known in sweetpotato or it is governed\\u000a by complex inheritance. Sweetpotato is clonally propagated, highly heterozygous, polyploid and out-crossing – in other words,\\u000a a challenging crop to

  9. Developing genetic competency in undergraduate nursing students through the context of human disease and the constructivist framework

    Microsoft Academic Search

    Leta Meole Tribble

    2006-01-01

    Nowhere is the influence of genetics more extensively seen than in medicine. More precise diagnostic testing, prevention methods, and risk counseling have resulted from recent decades of genetics research, including the Human Genome Project (HGP). The expansion in genetics knowledge and related technologies will drive a major paradigm shift from diagnosis and treatment to preventive medicine. Resulting from this predicted

  10. [Patients with a diagnosis of pancreatitis and "dual diagnosis"].

    PubMed

    Just, Marek; Og?odek, Ewa

    2013-05-01

    "Dual diagnosis"is usually understood as the co-occurrence of mental illness and addiction to psychoactive substances. In the last two decades can be seen an increased interest of researchers and practitioners in theoretical aspects of dual diagnosis, their means of diagnosis and planning treatment programs. Establishing a medical diagnosis may be questioned whether psychopathological symptoms are due to psychoactive substance use or are caused by mental illness. Difficulty in recognizing the problem of dual diagnosis may be questioned whether psychopathological symptoms are due to psychoactive substance use or are caused by mental illness. Mental disorders coexisting with substance use are: schizophrenia, delusional disorder, bipolar one and disorder, anxiety disorders, personality disorders. The consumption of alcohol can cause a recurrence of mental illness and contribute to the need for rehospitalization. It is important to take the history of a patient who are suspected of co-occurrence of mental illness and addiction to psychoactive substances. PMID:23894784

  11. The diagnosis and consequences of Stickler syndrome.

    PubMed

    Webb, A C; Markus, A F

    2002-02-01

    The objective was to study the expressivity of Stickler syndrome in affected children and adults in the UK and to highlight issues for improving early diagnosis, treatment and counselling. A postal questionnaire survey of the 216 members of the Stickler Syndrome Support Group was carried out. Of the 153 (71%) who responded to the questionnaire, 48 (61%) of adults and 15 (20%) of children had experienced retinal detachment; 36 (49%) of the children and 18 (23%) of the adults were born with a cleft palate. Only 5 (7%) of the children and none of the adults had been diagnosed by a cleft surgeon, although 23 (31%) of the children had been diagnosed originally as having Pierre-Robin sequence. Only a third of the adults had been given any genetic counselling. Stickler syndrome is an under-diagnosed condition with profound consequences, particularly with respect to vision. Earlier diagnosis by the cleft team may help to reduce suffering and increase awareness of the condition. PMID:11883970

  12. De novo mutations in neurological and psychiatric disorders: effects, diagnosis and prevention

    PubMed Central

    2012-01-01

    Neurological and psychiatric disorders account for a considerable proportion of the global disease burden. Although there is a high heritability and a significant genetic component in these disorders, the genetic cause of most cases has yet to be identified. Advances in DNA sequencing allowing the analysis of the whole human genome in a single experiment have led to an acceleration of the discovery of the genetic factors associated with human disease. Recent studies using these platforms have highlighted the important role of de novo mutations in neurological and psychiatric disorders. These findings have opened new avenues into the understanding of genetic disease mechanisms. These discoveries, combined with the increasing ease with which we can sequence the human genome, have important implications for diagnosis, prevention and treatment. Here, we present an overview of the recent discovery of de novo mutations using key examples of neurological and psychiatric disorders. We also discuss the impact of technological developments on diagnosis and prevention. PMID:23009675

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

    PubMed Central

    Bianchi, Diana W

    2015-01-01

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

  14. Women's experience of telehealth cancer genetic counseling.

    PubMed

    Zilliacus, Elvira M; Meiser, Bettina; Lobb, Elizabeth A; Kirk, Judy; Warwick, Linda; Tucker, Katherine

    2010-10-01

    Telegenetics offers an alternative model of delivering genetic counseling to rural and outreach areas; however there is a dearth of qualitative research into the patient's experience. Twelve women who had received telemedicine genetic counseling for hereditary breast and/or ovarian cancer (HBOC) within the previous 12 months participated in a semi-structured telephone interview. The interview explored women's experience with telegenetics, satisfaction, perceived advantages and disadvantages and quality of the interaction with their genetic professionals. Overall women were highly satisfied with telegenetics. Telegenetics offered them convenience and reduced travel and associated costs. The majority of women described feeling a high degree of social presence, or rapport, with the off-site genetic clinician. One woman with a recent cancer diagnosis, reported that telemedicine was unable to meet her needs for psychosocial support. This finding highlights the need to be mindful of the psychosocial support needs of women with a recent diagnosis being seen via telegenetics. Patients attending for HBOC genetic counseling are generally highly satisfied with the technology and the interaction. Care should be taken, however, with patients with more complex psychosocial needs. PMID:20411313

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

    E-print Network

    Nazeen, Sumaiya

    2014-01-01

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

  16. What Is a Genetic Counselor?

    MedlinePLUS

    Genetic counselors You are here Home Testing & Services Working with healthcare professionals Genetic counselors Testing for genetic ... about genetic counselors and NSGC. What Is a Genetic Counselor? A genetic counselor is a kind of ...

  17. Current Diagnosis and Treatment of Anxiety Disorders

    PubMed Central

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

    2013-01-01

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

  18. [A cardiac rhabdomyome evoking the antenatal diagnosis of a Bourneville's tuberous sclerosis].

    PubMed

    Charif D'Ouazzane, M; Gueroui, I; Betaich, K; Bennani, R; Touati, Z; Haddour, L; Cherti, M

    2015-02-01

    Rare hereditary affection, the Bourneville's tuberous sclerosis (BTS) is an autosomal dominant inherited phakomatosis. Rhabdomyomes are the most frequent cardiac tumors in children and infants, they are one of the most premature modes of revelation of the STB. They sometimes allow to envisage the diagnosis in antenatal period at the same time as the genetic and neurological explorations. We report the diagnosis of a fetal BTS evoked by the antenatal discovery of a cardiac rhabdomyome. The antenatal cerebral explorations, realized by magnetic resonance imagery (MRI), put evidence cerebral localisations confirming the diagnosis. PMID:22621850

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

    SciTech Connect

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

    1994-09-01

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

  20. Biology 2250 Principles of Genetics

    E-print Network

    Innes, David J.

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

  1. Importance of genetic evaluation and testing in pediatric cardiomyopathy

    PubMed Central

    Tariq, Muhammad; Ware, Stephanie M

    2014-01-01

    Pediatric cardiomyopathies are clinically heterogeneous heart muscle disorders that are responsible for significant morbidity and mortality. Phenotypes include hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, left ventricular noncompaction and arrhythmogenic right ventricular cardiomyopathy. There is substantial evidence for a genetic contribution to pediatric cardiomyopathy. To date, more than 100 genes have been implicated in cardiomyopathy, but comprehensive genetic diagnosis has been problematic because of the large number of genes, the private nature of mutations, and difficulties in interpreting novel rare variants. This review will focus on current knowledge on the genetic etiologies of pediatric cardiomyopathy and their diagnostic relevance in clinical settings. Recent developments in sequencing technologies are greatly impacting the pace of gene discovery and clinical diagnosis. Understanding the genetic basis for pediatric cardiomyopathy and establishing genotype-phenotype correlations may help delineate the molecular and cellular events necessary to identify potential novel therapeutic targets for heart muscle dysfunction in children. PMID:25429328

  2. Molecular Diagnosis of Congenital Adrenal Hyperplasia in Iran: Focusing on CYP21A2 Gene

    PubMed Central

    Rabbani, Bahareh; Mahdieh, Nejat; Haghi Ashtiani, Mohammad-Taghi; Akbari, Mohammad-Taghi; Rabbani, Ali

    2011-01-01

    Congenital adrenal hyperplasia (CAH) is characterized by impaired biosynthesis of cortisol. 21-hydroxylase deficiency is the most common cause of CAH affecting 1 in 10000-15000 live births over the world. The frequency of the disorder is very high in Iran due to frequent consanguineous marriages. Although biochemical tests are used to confirm the clinical diagnosis, molecular methods could help to define accurate diagnosis of the genetic defect. Recent molecular approaches such as polymerase chain reaction based methods could be used to detect carriers and identify different genotypes of the affected individuals in Iran which may cause variable degrees of clinical expression of the condition. Molecular tests are also applied for prenatal diagnosis, and genetic counseling of the affected families. Here, we are willing to delineate mechanisms underlying the disease, genetic causes of CAH, genetic approaches being used in the country and recommendations for health care improvement on the basis of the molecular and clinical genetics to control and diminish such a high prevalent disorder in Iran. Also, the previous studies on CAH in Iran are gathered and a diagnostic algorithm for the genetic causes is proposed. PMID:23056780

  3. Automatic Diagnosis of Pathological Myopia from Heterogeneous Biomedical Data

    PubMed Central

    Zhang, Zhuo; Xu, Yanwu; Liu, Jiang; Wong, Damon Wing Kee; Kwoh, Chee Keong; Saw, Seang-Mei; Wong, Tien Yin

    2013-01-01

    Pathological myopia is one of the leading causes of blindness worldwide. The condition is particularly prevalent in Asia. Unlike myopia, pathological myopia is accompanied by degenerative changes in the retina, which if left untreated can lead to irrecoverable vision loss. The accurate diagnosis of pathological myopia will enable timely intervention and facilitate better disease management to slow down the progression of the disease. Current methods of assessment typically consider only one type of data, such as that from retinal imaging. However, different kinds of data, including that of genetic, demographic and clinical information, may contain different and independent information, which can provide different perspectives on the visually observable, genetic or environmental mechanisms for the disease. The combination of these potentially complementary pieces of information can enhance the understanding of the disease, providing a holistic appreciation of the multiple risks factors as well as improving the detection outcomes. In this study, we propose a computer-aided diagnosis framework for Pathological Myopia diagnosis through Biomedical and Image Informatics(PM-BMII). Through the use of multiple kernel learning (MKL) methods, PM-BMII intelligently fuses heterogeneous biomedical information to improve the accuracy of disease diagnosis. Data from 2,258 subjects of a population-based study, in which demographic and clinical information, retinal fundus imaging data and genotyping data were collected, are used to evaluate the proposed framework. The experimental results show that PM-BMII achieves an AUC of 0.888, outperforming the detection results from the use of demographic and clinical information 0.607 (increase , ), genotyping data 0.774 (increase , ) or imaging data 0.852 (increase , ) alone. The accuracy of the results obtained demonstrates the feasibility of using heterogeneous data for improved disease diagnosis through our proposed PM-BMII framework. PMID:23799040

  4. [Multiple sclerosis: diagnosis, clinical course and differential diagnosis].

    PubMed

    Tomioka, Ryo; Matsui, Makoto

    2014-11-01

    Disease modifying treatment for multiple sclerosis has improved both relapse rate and prognosis. The diagnostic criteria of McDonald were designed for early diagnosis, with a crucial role for magnetic resonance imaging in the 2010 revision, as dissemination in space and time can be established by a single scan. These criteria are likely applicable in pediatric, Asian, and Latin America populations, and include neuromyelitis optica as a differential diagnosis. With recent modifications for widespread use, diagnostic sensitivity and specificity have been improved. Nevertheless, clinical and imaging red flags for atypical manifestations are needed for exclusion of alternative diagnosis. PMID:25518377

  5. Biology 4250 Evolutionary Genetics

    E-print Network

    Innes, David J.

    8. Sex and Evolution 9. Conservation Genetics 10. Human Evolutionary Genetics Estimating genetic1 Biology 4250 Evolutionary Genetics Fall 2009 Dr. David Innes Outline of topics: 1. Introduction/History of Interest in Genetic Variation 2. Types of Molecular Markers 3. Molecular Markers in Ecology and Evolution 4

  6. [Oesophageal cancer--diagnosis].

    PubMed

    Menges, M

    2004-12-01

    The incidence of oesophageal cancer has been rising for the past decades in the western world due to the rapid increase of oesophageal adenocarcinoma. Strategy and extent of the diagnostic work up in case of suspected oesophageal cancer should be focussed on the therapeutic consequences which have to be drawn in the individual patient. Upper endoscopy including biopsy will provide the diagnosis and the location of the tumour, computed tomography and transcutaneous sonography are used to rule out distant metastases. Endoscopic ultrasound is the tool of choice to obtain an exact locoregional staging - an experienced investigator may correctly classify the tumour according to the T-N-categories in about 80% of the cases. To define early cancers restricted to the mucosa, which may be suitable for local ablative therapy, high-resolution endosonography is essential. Intravital staining methods may help to delineate flat or multifocal cancers, they are also used to better recognise dysplastic foci in a Barrett-segment. To rule out osseous metastases a bone scintigraphy is indicated. In tumours located proximal to the bifurcation a bronchoscopy completes the diagnostic procedures, in case of advanced tumours of the oesophagogastric junction laparoscopy may be performed to rule out peritoneal carcinosis. PMID:15630986

  7. Diagnosis of autoimmune pancreatitis

    PubMed Central

    Matsubayashi, Hiroyuki; Kakushima, Naomi; Takizawa, Kohei; Tanaka, Masaki; Imai, Kenichiro; Hotta, Kinichi; Ono, Hiroyuki

    2014-01-01

    Autoimmune pancreatitis (AIP) is a distinct form of chronic pancreatitis that is increasingly being reported. The presentation and clinical image findings of AIP sometimes resemble those of several pancreatic malignancies, but the therapeutic strategy differs appreciably. Therefore, accurate diagnosis is necessary for cases of AIP. To date, AIP is classified into two distinct subtypes from the viewpoints of etiology, serum markers, histology, other organ involvements, and frequency of relapse: type 1 is related to IgG4 (lymphoplasmacytic sclerosing pancreatitis) and type 2 is related to a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis). Both types of AIP are characterized by focal or diffuse pancreatic enlargement accompanied with a narrowing of the main pancreatic duct, and both show dramatic responses to corticosteroid. Unlike type 2, type 1 is characteristically associated with increasing levels of serum IgG4 and positive serum autoantibodies, abundant infiltration of IgG4-positive plasmacytes, frequent extrapancreatic lesions, and relapse. These findings have led several countries to propose diagnostic criteria for AIP, which consist of essentially similar diagnostic items; however, several differences exist for each country, mainly due to differences in the definition of AIP and the modalities used to diagnose this disease. An attempt to unite the diagnostic criteria worldwide was made with the publication in 2011 of the international consensus diagnostic criteria for AIP, established at the 2010 Congress of the International Association of Pancreatology (IAP). PMID:25469024

  8. Diagnosis of acute rhinosinusitis.

    PubMed

    Esposito, Susanna; Marchisio, Paola; Tenconi, Rossana; Tagliaferri, Laura; Albertario, Giada; Patria, Maria Francesca; Principi, Nicola

    2012-08-01

    Rhinosinusitis is almost always a complication of a viral infection involving the upper respiratory tract. A common cold is the first symptom of rhinosinusitis, but infectious processes involving the nose inevitably affect the paranasal sinuses because of their anatomical contiguity. The symptoms remain those of a common cold as long as nasal phlogosis is moderate and the ostia between the nose and sinuses are patent. If the inflammation is intense, edema may obliterate the ostia and isolate the sinuses, thus stopping the removal of the exudates. The duration of symptoms makes it possible to distinguish acute (10-30?days) from subacute (30-90?days) and chronic rhinosinusitis (>90?days). The diagnosis of rhinosinusitis should only be based on anamnestic and clinical criteria in children with serious or persistent symptoms of upper respiratory tract infection, or which appear within a short time of an apparent recovery. Computed tomography and magnetic resonance images of the paranasal sinuses should be reserved for children reasonably considered to be candidates for surgery. Antibiotics are recommended in cases of mild acute bacterial rhinosinusitis as a means of accelerating the resolution of symptoms. The use of antibiotics is mandatory in severe acute bacterial rhinosinusitis to cure the disease and avoid the possible onset of severe complications. PMID:22762849

  9. Genetic markers to predict polygenic disease

    Microsoft Academic Search

    David J. Galton

    1999-01-01

    Many genetic markers that relate to common multifactorial disease in adults have been identified during the past 15 years.\\u000a Their use as adjuncts for the diagnosis, prognosis, prediction of disease or targeting therapy for these disorders has commenced;\\u000a good examples being the Factor V Leiden mutation for venous-thromboembolism, lipoprotein lipase mutations for hypertriglyceridemia\\u000a and the apolipoprotein E4 variant for Alzheimer’s

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

    PubMed Central

    Sinkov, Vladamir; Cymet, Tyler

    2003-01-01

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

  11. Genetic testing in the epilepsies—Report of the ILAE Genetics Commission

    PubMed Central

    Ottman, Ruth; Hirose, Shinichi; Jain, Satish; Lerche, Holger; Lopes-Cendes, Iscia; Noebels, Jeffrey L.; Serratosa, José; Zara, Federico; Scheffer, Ingrid E.

    2010-01-01

    SUMMARY In this report, the International League Against Epilepsy (ILAE) Genetics Commission discusses essential issues to be considered with regard to clinical genetic testing in the epilepsies. Genetic research on the epilepsies has led to the identification of more than 20 genes with a major effect on susceptibility to idiopathic epilepsies. The most important potential clinical application of these discoveries is genetic testing: the use of genetic information, either to clarify the diagnosis in people already known or suspected to have epilepsy (diagnostic testing), or to predict onset of epilepsy in people at risk because of a family history (predictive testing). Although genetic testing has many potential benefits, it also has potential harms, and assessment of these potential benefits and harms in particular situations is complex. Moreover, many treating clinicians are unfamiliar with the types of tests available, how to access them, how to decide whether they should be offered, and what measures should be used to maximize benefit and minimize harm to their patients. Because the field is moving rapidly, with new information emerging practically every day, we present a framework for considering the clinical utility of genetic testing that can be applied to many different syndromes and clinical contexts. Given the current state of knowledge, genetic testing has high0020clinical utility in few clinical contexts, but in some of these it carries implications for daily clinical practice. PMID:20100225

  12. Genetic testing in the epilepsies--report of the ILAE Genetics Commission.

    PubMed

    Ottman, Ruth; Hirose, Shinichi; Jain, Satish; Lerche, Holger; Lopes-Cendes, Iscia; Noebels, Jeffrey L; Serratosa, José; Zara, Federico; Scheffer, Ingrid E

    2010-04-01

    In this report, the International League Against Epilepsy (ILAE) Genetics Commission discusses essential issues to be considered with regard to clinical genetic testing in the epilepsies. Genetic research on the epilepsies has led to the identification of more than 20 genes with a major effect on susceptibility to idiopathic epilepsies. The most important potential clinical application of these discoveries is genetic testing: the use of genetic information, either to clarify the diagnosis in people already known or suspected to have epilepsy (diagnostic testing), or to predict onset of epilepsy in people at risk because of a family history (predictive testing). Although genetic testing has many potential benefits, it also has potential harms, and assessment of these potential benefits and harms in particular situations is complex. Moreover, many treating clinicians are unfamiliar with the types of tests available, how to access them, how to decide whether they should be offered, and what measures should be used to maximize benefit and minimize harm to their patients. Because the field is moving rapidly, with new information emerging practically every day, we present a framework for considering the clinical utility of genetic testing that can be applied to many different syndromes and clinical contexts. Given the current state of knowledge, genetic testing has high clinical utility in few clinical contexts, but in some of these it carries implications for daily clinical practice. PMID:20100225

  13. The genetics of cardiomyopathies: What clinicians should know

    Microsoft Academic Search

    Rahul Deo; Calum A. MacRae

    2007-01-01

    Primary myocardial diseases, or cardiomyopathies, affect millions of individuals worldwide. Although there are sizable environmental\\u000a contributors to the etiology of these diseases, many cardiomyopathies have a high degree of heritability and, thus, genetic\\u000a aspects of diagnosis and therapy warrant special consideration. The past two decades have seen enormous progress in elucidating\\u000a the epidemiology, genetic architecture, and pathophysiology of these diseases.

  14. Difficult prenatal diagnosis: fetal coarctation

    PubMed Central

    Buyens, A.; Gyselaers, W.; Coumans, A.; Al Nasiry, S.; Willekes, C.; Boshoff, D.; Frijns, J.-P.; Witters, I.

    2012-01-01

    The prenatal diagnosis of fetal coarctation is still challenging. It is mainly suspected by ventricular disproportion (smaller left ventricle than right ventricle). The sensitivity of ventricular discrepancy is however moderate for the diagnosis of coarctation and there is a high false positive rate. Prenatal diagnosis of coarctation is important because the delivery can be arranged in a centre with a pediatric cardiac intensive careand this reduces postnatal complications and longterm morbidity. For many years the prenatal diagnosis of coarctation has been investigated to improve specificity and sensitivity by several of measurements. This article reviews all relevant articles from 2000 until 2011 searching pubmed and the reference list of interesting articles. An overview of specific measurements and techniques that can improve the diagnosis of coarctation has been made, such as the isthmus diameter, ductal diameter, isthmus/ductal ratio, z-scores derived from measurements of the distal aortic isthmus and arterial duct, the presence of a shelf andisthmal flow disturbance. Also 3-dimensional (3D) and 4-dimensional (4D) imaging with or without STIC has been suggested to be used as newer techniques to improve diagnosis of coarctation in fetal life. Although more methods regarding prenatal diagnosis of coarctationare being investigated, the ultrasound specialist remains challenged to correctly diagnose this cardiac anomaly in prenatal life. PMID:24753914

  15. Diagnosis and complementary examinations.

    PubMed

    Menghini, Moreno; Duncan, Jacque L

    2014-01-01

    Development of neuroprotective therapies requires an understanding of the mechanisms of retinal degeneration and a way to monitor response to treatment. With the increasing availability of genetic testing, precise characterization of the retinal degeneration phenotype is essential. This chapter covers standard and innovative diagnostic techniques and complementary examinations needed for the evaluation and treatment of retinal degenerative diseases. It aims to provide an overview of functional and structural diagnostic tools for the evaluation of retinal degenerative diseases, but is not intended as a comprehensive reference. Subjective assessment of visual function includes psychophysical tests, such as perimetry and microperimetry. Electrophysiology tests, such as the electroretinogram and electro-oculogram, are crucial in the assessment of retinal degenerative diseases and provide an objective assessment of global photoreceptor and retinal pigment epithelial cell function. Retinal structural measures are correlated with measures of retinal function to characterize the disease phenotype, including fundus photography using color, near-infrared, and autofluorescence imaging. Ocular perfusion can be assessed using fluorescein, indocyanine green, and noninvasive angiography. Optical coherence tomography provides information about retinal structure. Resolution of all images of retinal structure can be improved using adaptive optics, which permits visualization of individual photoreceptors and retinal pigment epithelial cells in the macula. PMID:24732761

  16. Familial Evaluation for Diagnosis of Arrhythmogenic Right Ventricular Dysplasia

    PubMed Central

    Palmisano, Brian T.; Rottman, Jeffrey N.; Wells, Quinn S.; DiSalvo, Thomas G.; Hong, Charles C.

    2011-01-01

    Most sudden cardiac deaths in young athletes are caused by previously undetected inherited cardiac diseases. Here, we report a case of a young male athlete in whom a presumptive diagnosis of hypertrophic cardiomyopathy (HCM) was made following a near sudden cardiac death. Although his imaging studies initially suggested HCM, a detailed clinical and genetic evaluation of the patient and his asymptomatic father led to the diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVD) in both. DNA sequencing revealed that each individual was heterozygous for two rare variants in the PKP2 and DSC2 genes, both of which were previously shown to be associated with ARVD and to encode desmosomal proteins, i.e. the previously reported splicing variant c2489 + 1A>G in the PKP2 gene and the novel p.I109M variant in the DSC2 gene. Imaging and electrophysiologic studies further supported a diagnosis of ARVD in the father. This case highlights the importance of detailed clinical evaluation and genetic testing of family members when dealing with sudden cardiac death or unexplained cardiomyopathies in the young. PMID:21822014

  17. Onychomycosis: Diagnosis and management.

    PubMed

    Singal, Archana; Khanna, Deepshikha

    2011-01-01

    Onychomycosis is a common nail ailment associated with significant physical and psychological morbidity. Increased prevalence in the recent years is attributed to enhanced longevity, comorbid conditions such as diabetes, avid sports participation, and emergence of HIV. Dermatophytes are the most commonly implicated etiologic agents, particularly Trichophyton rubrum and Trichophyton mentagrophytes var. interdigitale, followed by Candida species and non dermatophytic molds (NDMs). Several clinical variants have been recognized. Candida onychomycosis affects fingernails more often and is accompanied by paronychia. NDM molds should be suspected in patients with history of trauma and associated periungual inflammation. Diagnosis is primarily based upon KOH examination, culture and histopathological examinations of nail clippings and nail biopsy. Adequate and appropriate sample collection is vital to pinpoint the exact etiological fungus. Various improvisations have been adopted to improve the fungal isolation. Culture is the gold standard, while histopathology is often performed to diagnose and differentiate onychomycosis from other nail disorders such as psoriasis and lichen planus. Though rarely used, DNA-based methods are effective for identifying mixed infections and quantification of fungal load. Various treatment modalities including topical, systemic and surgical have been used.Topically, drugs (ciclopirox and amorolfine nail lacquers) are delivered through specialized transungual drug delivery systems ensuring high concentration and prolonged contact. Commonly used oral therapeutic agents include terbinafine, fluconazole, and itraconazole. Terbinafine and itraconazole are given as continuous as well as intermittent regimes. Continuous terbinafine appears to be the most effective regime for dermatophyte onychomycosis. Despite good therapeutic response to newer modalities, long-term outcome is unsatisfactory due to therapeutic failure, relapse, and reinfection. To combat the poor response, newer strategies such as combination, sequential, and supplementary therapies have been suggested. In the end, treatment of special populations such as diabetic, elderly, and children is outlined. PMID:22016272

  18. The genetic tyrosinemias.

    PubMed

    Scott, C Ronald

    2006-05-15

    The genetic tyrosinemias are characterized by the accumulation of tyrosine in body fluids and tissues. The most severe form of tyrosinemia, Type I, is a devastating disorder of childhood that causes liver failure, painful neurologic crises, rickets, and hepatocarcinoma. This disorder is caused by a deficiency of fumarylacetoacetate hydrolase (FAH). If untreated, death typically occurs at less than 2 years of age, with some chronic forms allowing longer survival. It has a prevalence of about 1 in 100,000 newborns in the general population. Oculocutaneous tyrosinemia, Type II, is caused by a deficiency of tyrosine aminotransferase (TAT). It clinically presents with hyperkeratotic plaques on the hands and soles of the feet and photophobia due to deposition of tyrosine crystals within the cornea. Tyrosinemia Type III is an extremely rare disorder caused by a deficiency of 4-hydroxyphenylpyruvic dioxygenase. It has been associated with ataxia and mild mental retardation. These disorders are diagnosed by observing elevated tyrosine by plasma amino acid chromatography and characteristic tyrosine metabolites by urine organic acid analysis. In tyrosinemia Type I, methionine is also elevated, reflecting impaired hepatocellular function. Urine organic acids show elevated p-hydroxy-phenyl organic acids in each type of tyrosinemia, and the pathognomic succinylacetone in tyrosinemia Type I. Diagnosis can be confirmed by enzyme or molecular studies in tyrosinemia Type I. Therapy consists of a diet low in phenylalanine and tyrosine for each of the tyrosinemias and 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) for tyrosinemia Type I. PMID:16602095

  19. Inclusion-Body Myositis: Diagnosis

    MedlinePLUS

    ... MDA Partners in Progress Search form Search Inclusion-Body Myositis (IBM) Diagnosis As with other muscle diseases, a doctor diagnoses inclusion-body myositis (IBM) by considering the individual’s personal history, ...

  20. Diagnosis of Diabetes and Prediabetes

    MedlinePLUS

    ... to 5 p.m. eastern time, M-F Diabetes Disease Organizations There are many organizations who provide ... PDF, 293 KB). Alternate Language URL Diagnosis of Diabetes and Prediabetes Page Content On this page: What ...

  1. Spinal Tuberculosis: Diagnosis and Management

    PubMed Central

    Rasouli, Mohammad R.; Mirkoohi, Maryam; Vaccaro, Alexander R.; Yarandi, Kourosh Karimi

    2012-01-01

    The spinal column is involved in less than 1% of all cases of tuberculosis (TB). Spinal TB is a very dangerous type of skeletal TB as it can be associated with neurologic deficit due to compression of adjacent neural structures and significant spinal deformity. Therefore, early diagnosis and management of spinal TB has special importance in preventing these serious complications. In order to extract current trends in diagnosis and medical or surgical treatment of spinal TB we performed a narrative review with analysis of all the articles available for us which were published between 1990 and 2011. Althoug h the development of more accurate imaging modalities such as magnetic resonance imaging and advanced surgical techniques have made the early diagnosis and management of spinal TB much easier, these are still very challenging topics. In this review we aim to discuss the diagnosis and management of spinal TB based on studies with acceptable design, clearly explained results and justifiable conclusions. PMID:23275816

  2. DCTD — Cancer Diagnosis Program (CDP)

    Cancer.gov

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

  3. Foundations Algorithm Components Numerical Optimization Genetic Programming Genetic Algorithms

    E-print Network

    Kjellström, Hedvig

    Foundations Algorithm Components Numerical Optimization Genetic Programming Genetic Algorithms Foundations Algorithm Components Numerical Optimization Genetic Programming 1 Foundations 2 Algorithm Programming Example Foundations Algorithm Components Numerical Optimization Genetic Programming Genetic

  4. Foundations Algorithm Components Numerical Optimization Genetic Programming Genetic Algorithms

    E-print Network

    Kjellström, Hedvig

    Foundations Algorithm Components Numerical Optimization Genetic Programming Genetic Algorithms #12;Foundations Algorithm Components Numerical Optimization Genetic Programming 1 Foundations 2 Algorithm Programming Example #12;Foundations Algorithm Components Numerical Optimization Genetic Programming Genetic

  5. A difficult diagnosis: acute histoplasmosis

    PubMed Central

    Pizanis, Charles; Davis, John

    2012-01-01

    A 43-year-old male with deceased donor kidney transplantation presented with fever of unknown etiology and underwent an extensive workup. The diagnosis of histoplasmosis was made after biopsy of a positron emission tomography-positive subcarinal lymph node showed non-caseating granulomas with a positive stain for yeast. The diagnosis was confirmed when fevers remitted with initiation of appropriate anti-fungal therapy.

  6. Early diagnosis of dementia: neuropsychology

    Microsoft Academic Search

    Florence Pasquier

    1999-01-01

    Neuropsychology contributes greatly to the diagnosis of dementia. Cognitive deficits can be detected several years before\\u000a the clinical diagnosis of dementia. The neuropsychological profile may indicate the underlying neuropathology. Neuropsychological\\u000a assessment at an early stage of dementia has two goals: (a) to determine a memory disorder, not always associated with a memory\\u000a complaint, and (b) to characterize the memory disorder

  7. Pruritus ani: diagnosis and treatment.

    PubMed

    Nasseri, Yosef Y; Osborne, Marc C

    2013-12-01

    Pruritus ani is a common condition with multiple causes. Primary causes are thought to be fecal soiling or food irritants. Secondary causes include malignancy, infections including sexually transmitted diseases, benign anorectal diseases, systemic diseases, and inflammatory conditions. A broad differential diagnosis must be considered. A reassessment of the diagnosis is required if symptoms or findings are not responsive to therapy. The pathophysiology of itching, an overview of primary and secondary causes, and various treatment options are reviewed. PMID:24280401

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

    ERIC Educational Resources Information Center

    Hornstein, Shana

    2011-01-01

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

  9. An Evolutionary Computational Approach to Probabilistic Neural Network with Application to Hepatic Cancer Diagnosis

    Microsoft Academic Search

    Florin Gorunescu; Marina Gorunescu; Elia El-darzi; Smaranda Gorunescu

    2005-01-01

    The performance of a probabilistic neural network is strongly influenced by the smoothing parameter. This paper introduces an evolutionary approach based on genetic algorithm to optimise the search of the smoothing parameter in a modified probabilistic neural network. A Java implementation is introduced and the computational results showed the viability of this hybrid approach to determine the optimum diagnosis for

  10. Summary of current research interests Management and molecular diagnosis of inherited retinal diseases

    E-print Network

    Saunders, Mark

    Summary of current research interests Management and molecular diagnosis of inherited retinal on retinal function Susceptibility genetic factors in age-related macular degeneration and human refractive: 020 7608 6830 Email: andrew.webster@ucl.ac.uk Research Projects Retinitis pigmentosa: With colleagues

  11. Toward the Use of LIBS for the Clinical Diagnosis of Disease-

    E-print Network

    Rehse, Steven J.

    Toward the Use of LIBS for the Clinical Diagnosis of Disease- Causing Pathogens Steven J. Rehse WSU bacteria? 4 ways · genetic · serological (antigenic) · microbiological · compositional ­ LIBS ­ Raman ­ MALDI-TOF-MS #12;#12;things that make a LIBS-based technology unique* · lack of complicated sample

  12. Recent developments of induction motor drives fault diagnosis using AI techniques

    Microsoft Academic Search

    Fiorenzo Filippetti; Giovanni Franceschini; Carla Tassoni; Peter Vas

    2000-01-01

    This paper presents a review of the developments in the field of diagnosis of electrical machines and drives based on artificial intelligence (AI). It covers the application of expert systems, artificial neural networks (ANNs), and fuzzy logic systems that can be integrated into each other and also with more traditional techniques. The application of genetic algorithms is considered as well.

  13. Hypertrophic cardiomyopathy: from genetics to treatment

    PubMed Central

    Marian, Ali J.

    2010-01-01

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

  14. Molecular genetics of Mycobacterium tuberculosis in relation to the discovery of novel drugs and vaccines

    Microsoft Academic Search

    Bavesh D Kana; Valerie Mizrahi

    2004-01-01

    Genetic systems that allow mycobacterial genomes to be mutagenized in a targeted or random fashion have provided the means for developing new tools for the diagnosis, prevention and treatment of tuberculosis by allowing potential targets to be identified and validated. In this review, we highlight key historical developments in the field of mycobacterial genetics, which have yielded the powerful repertoire

  15. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease

    Microsoft Academic Search

    Gary W. Small; Linda M. Ercoli; Daniel H. S. Silverman; S.-C. Huang; Scott Komo; Susan Y. Bookheimer; Helen Lavretsky; Karen Miller; Prabha Siddarth; Natalie L. Rasgon; John C. Mazziotta; Sanjaya Saxena; H. M. Wu; Jeffrey L. Cummings; Ann M. Saunders; Pericak Vance Ma; Allen D. Roses; Phelps Me

    2000-01-01

    The major known genetic risk for Alzheimer's disease (AD), apo- lipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investi- gated cerebral metabolic rates by using positron emission tomog- raphy in middle-aged and older

  16. Biology 2250 Principles of Genetics

    E-print Network

    Innes, David J.

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

  17. Genetics in public health: Rarely explored

    PubMed Central

    Aswini, Y. B.; Varun, S.

    2010-01-01

    The availability and the integration of genetic information into our understanding of normal and abnormal growth and development are driving important changes in health care. These changes have fostered the hope that the availability of genetic information will promote a better understanding of disease etiology and permit early, even pre-symptomatic diagnosis and preventive intervention to avoid disease onset. Hence, our aim was to review and provide the insight into the role of genetics in public health and its scope as well as barriers. The use of genetics along with their goals and essential public health functions are discussed. From the era of eugenics to the present era, this area has seen many turns in which geneticists have put through their effort to tie together the strings of both molecular genetics and public health. Though still the dark clouds of eugenics, the predictive power of genes, genetic reductionism, non-modifiable risk factors, individuals or populations, resource allocation, commercial imperative, discrimination and understanding and education are hanging above. The technological and scientific advances that have fundamentally changed our perception of human diseases fuel the expectations for this proactive health. PMID:21031051

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

    PubMed Central

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

    2013-01-01

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

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

    SciTech Connect

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

    1997-03-01

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

  20. Peripartum cardiomyopathy in Africa: challenges in diagnosis, prognosis, and therapy.

    PubMed

    Tibazarwa, Kemi; Sliwa, Karen

    2010-01-01

    Peripartum cardiomyopathy (PPCM) is a form of heart failure affecting women of childbearing age, which can be associated with considerable mortality and chronic debilitating disease. Most patients present with acute postpartal heart failure that resembles the clinical presentation of idiopathic dilated cardiomyopathy. Historically, patients with PPCM have shown high rates of rapid recovery, with 6-month recovery rates averaging at 50%. However, recent prospective long-term follow-up of patients with PPCM in developing societies suggest recovery occurring only well into the second year after diagnosis, and recovery is poorly predicted by baseline left ventricular function. Beyond any potentially inherent factors contributing to poorer outcomes of patients with PPCM in developing societies, prognosis in these settings will continue to lag behind as the challenges faced to optimizing diagnosis remain immense. New insights into the role of inflammatory, apoptotic, and other genetic pathways may improve prognosis through the early detection and more targeted treatment of PPCM. PMID:20109601

  1. Acquired ataxias: the clinical spectrum, diagnosis and management.

    PubMed

    Nachbauer, Wolfgang; Eigentler, Andreas; Boesch, Sylvia

    2015-05-01

    Acquired ataxias represent a large group of disorders defined by the common clinical feature of ataxia and the absence of a clear genetic basis for it. Based on the aetiology, the group can be subdivided into autoimmune, toxic, infectious and vitamin deficiency causes. Cerebellar ataxia may occur as an isolated syndrome in this spectrum of disorders but is often accompanied by additional neurological manifestations. Clinical work-up is challenging and mainly includes biochemical analyses, whereas imaging is of minor significance. Diagnosis is essential as many of these disorders represent potential treatable conditions and early therapy may prevent progressive cerebellar ataxia. The clinical findings, the implications for diagnosis and management of this heterogeneous group of disorders are discussed in this review. PMID:25808499

  2. [Differential diagnosis and work up of chronic leg ulcers].

    PubMed

    Spoljar, Sanja

    2014-10-01

    Many factors contribute to the pathogenesis of leg ulcers. The main causes are chronic venous insufficiency, peripheral arterial occlusive disease (PAOD) and diabetes. Some leg ulcers are caused by combinations of these well-known etiologic factors. The most common cause of PAOD is arteriosclerosis. In diabetic patients, distal symmetric neuropathy and peripheral vascular disease are probably the most important etiologic factors in the development of leg ulcers. Less frequent causes of chronic leg ulcers are hematologic diseases, autoimmune diseases, genetic defects, infections, primary skin disease, cutaneous malignant diseases, use of some medications and therapeutic procedures, and numerous exogenous factors. Diagnosis of leg ulcer is made upon medical history, clinical picture, palpation of arteries, functional testing and serologic testing. Device-based diagnostic testing should be performed for additional clarification. Also, lesion biopsy should be taken for histopathology, direct immunofluorescence, bacteriology and mycology. The knowledge of differential diagnosis is essential for ensuring treatment success in a patient with leg ulcer. PMID:25326987

  3. Biomarkers in the diagnosis of ADHD--promising directions.

    PubMed

    Faraone, Stephen V; Bonvicini, Cristian; Scassellati, Catia

    2014-11-01

    The etiology and pathogenesis of attention-deficit/hyperactivity disorder (ADHD) are unclear and a more valid diagnosis would certainly be welcomed. Starting from the literature, we built an hypothetical pyramid representing a putative set of biomarkers where, at the top, variants in DAT1 and DRD4 genes are the best candidates for their associations to neuropsychological tasks, activation in specific brain areas, methylphenidate response and gene expression levels. Interesting data come from the noradrenergic system (norepinephrine transporter, norepinephrine, 3-methoxy-4-hydroxyphenylglycol, monoamine oxidase, neuropeptide Y) for their altered peripheral levels, their association with neuropsychological tasks, symptomatology, drugs effect and brain function. Other minor putative genetic biomarkers could be dopamine beta hydroxylase and catechol-O-methyltransferase. In the bottom, we placed endophenotype biomarkers. A more deep integration of "omics" sciences along with more accurate clinical profiles and new high-throughput computational methods will allow us to identify a better list of biomarkers useful for diagnosis and therapies. PMID:25298126

  4. Importance of Classical Morphology in the Diagnosis of Myelodysplastic Syndrome

    PubMed Central

    Invernizzi, Rosangela; Quaglia, Federica; Porta, Matteo Giovanni Della

    2015-01-01

    Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders characterized by dysplastic, ineffective, clonal and neoplastic hematopoiesis. MDS represent a complex hematological problem: differences in disease presentation, progression and outcome have necessitated the use of classification systems to improve diagnosis, prognostication, and treatment selection. However, since a single biological or genetic reliable diagnostic marker has not yet been discovered for MDS, quantitative and qualitative dysplastic morphological alterations of bone marrow precursors and peripheral blood cells are still fundamental for diagnostic classification. In this paper, World Health Organization (WHO) classification refinements and current minimal diagnostic criteria proposed by expert panels are highlighted, and related problematic issues are discussed. The recommendations should facilitate diagnostic and prognostic evaluations in MDS and selection of patients for new effective targeted therapies. Although, in the future, morphology should be supplemented with new molecular techniques, the morphological approach, at least for the moment, is still the cornerstone for the diagnosis and classification of these disorders. PMID:25960863

  5. The phenotypes of bipolar disorder: relevance for genetic investigations

    Microsoft Academic Search

    G M MacQueen; T Hajek; M Alda

    2005-01-01

    The search for susceptibility genes for bipolar disorder (BD) depends on appropriate definitions of the phenotype. In this paper, we review data on diagnosis and clinical features of BD that could be used in genetic studies to better characterize patients or to define homogeneous subgroups. Clinical symptoms, long-term course, comorbid conditions, and response to prophylactic treatment may define groups associated

  6. Network management and system-level diagnosis

    Microsoft Academic Search

    Sailesh Chutani; Henri J. Nussbaumer

    1995-01-01

    Fault management, which consists of fault detection, diagnosis, and recovery is one of the key goals of network management. We consider an application of system-level diagnosis concepts to the problem of fault diagnosis in networks. Since the primary function of the nodes in a communication network is to route messages, the diagnosis is done with respect to the ability of

  7. Review of fault diagnosis in control systems

    Microsoft Academic Search

    Aishe Shui; Weimin Chen; Peng Zhang; Shunren Hu; Xiaowei Huang

    2009-01-01

    In this paper, we review the major achievements on the research of fault diagnosis in control systems (FDCS) from three aspects which including fault detection, fault isolation and hybrid intelligent fault diagnosis. Fault detection and isolation (FDI) are two important stages in the diagnosis process while hybrid intelligent fault diagnosis is the hot issue in current research field. The particular

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

    SciTech Connect

    Not Available

    1987-09-04

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

  9. 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 of Medicine at Wayne State University offers a fully accredited Master's level graduate program in genetic

  10. Interactive Genetics Tutorial Project.

    ERIC Educational Resources Information Center

    Wisconsin Univ., Madison. Dept. of Curriculum and Instruction.

    The Interactive Genetics Tutorial (IGT) project and the Intelligent Tutoring System for the IGT project named MENDEL supplement genetics instruction in biology courses by providing students with experience in designing, conducting, and evaluating genetics experiments. The MENDEL software is designed to: (1) simulate genetics experiments that…

  11. Biology 4250 Evolutionary Genetics

    E-print Network

    Innes, David J.

    and Evolution 9. Conservation Genetics 10. Human Evolutionary Genetics Course Information Lecture format: Mon1 Biology 4250 Evolutionary Genetics Fall 2009 Dr David InnesDr. David Innes Course Webpage: http://www.mun.ca/biology/dinnes/B4250_09/Biol4250.html Desire2Learn (login): https://online.mun.ca/ Evolutionary Genetics Goals

  12. Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors

    PubMed Central

    Weiner, Shoshana J; Neragi-Miandoab, Siyamek

    2008-01-01

    Malignant pleural mesothelioma (MPM) is a rare, aggressive tumor for which no effective therapy exists despite the discovery of many possible molecular and genetic targets. Many risk factors for MPM development have been recognized including environmental exposures, genetic susceptibility, viral contamination, and radiation. However, the late stage of MPM diagnosis and the long latency that exists between some exposures and diagnosis have made it difficult to comprehensively evaluate the role of risk factors and their downstream molecular effects. In this review, we discuss the current molecular and genetic contributors in MPM pathogenesis and the risk factors associated with these carcinogenic processes. PMID:18662397

  13. Diagnosis of Trace Toxic Uranium Ions in Organic Liver Cell

    PubMed Central

    Ly, Suw Young; Pack, Eun Chul

    2014-01-01

    Uranium is toxic and radioactive traces of it can be found in natural water and soils. High concentrations of it in biological systems cause genetic disorders and diseases. For the in vivo diagnosis, micro and nano range detection limits are required. Here, an electrochemical assay for trace toxic uranium was searched using stripping voltammetry. Renewable and simplified graphite pencils electrode (PE) was used in a three-electrode cell system. Seawater was used instead of an electrolyte solution. This setup can yield good results and the detection limit was attained to be at 10 ?gL?1. The developed skill can be applied to organic liver cell. PMID:25071921

  14. Genetics and genomics of neuroblastoma.

    PubMed

    Capasso, Mario; Diskin, Sharon J

    2010-01-01

    Neuroblastoma is a pediatric cancer of the developing sympathetic nervous system that most often affects young children. It remains an important pediatric problem because it accounts for approximately 15% of childhood cancer mortality. The disease is clinically heterogeneous, with the likelihood of cure varying greatly according to age at diagnosis, extent of disease, and tumor biology. This extreme clinical heterogeneity reflects the complexity of genetic and genomic events associated with development and progression of disease. Inherited genetic variants and mutations that initiate tumorigenesis have been identified in neuroblastoma and multiple somatically acquired genomic alterations have been described that are relevant to disease progression. This chapter focuses on recent genome-wide studies that have utilized high-density single nucleotide polymorphism (SNP) genotyping arrays to discover genetic factors predisposing to tumor initiation such as rare mutations at locus 2p23 (in ALK gene) for familial neuroblastoma, common SNPs at 6p22 (FLJ22536 and FLJ44180) and 2q35 (BARD1), and a copy number polymorphism at 1q21.1 (NBPF23) for sporadic neuroblastoma. It also deals with well known and recently reported somatic changes in the tumor genome such as mutations, gain of alleles and activation of oncogenes, loss of alleles, or changes in tumor-cell ploidy leading to the diverse clinical behavior of neuroblastomas. Finally, this chapter reviews gene expression profiles of neuroblastoma associated with pathways of the signaling of neurotrophins and apoptotic factors that could have a role in neuroblastoma development and progression. Looking forward, a major challenge will be to understand how inherited genetic variation and acquired somatic alterations in the tumor genome interact to exact phenotypic differences in neuroblastoma, and cancer in general. PMID:20517688

  15. The role of FISH in prenatal diagnosis

    SciTech Connect

    Kulch, P.; Crandall, B.F.; Hsi, C. [Univ. of California, Los Angeles (United States)

    1994-09-01

    FISH provides a cytogenetic technique which is useful in defining de novo translocations, deletions, insertions, and marker chromosomes in prenatal diagnosis. While the cytogenetic interpretation may be improved with FISH, it may not resolve questions concerning prognosis and options which are genetic counseling issues. Two recent cases illustrate this. Case 1 involved a 45,X/46,X,+mar karyotype from amniocentesis. 22/50 cells had 46,X/46,X+mar; 28/50 cells had 45,X. The marker was smaller than a G. C banding did not confirm this as a Y. The father`s peripheral blood study was normal and his Y did not resemble the marker. It appeared likely that the marker was a structurally abnormal Y since male external genitalia were detected by fetal ultrasound. FISH using alpha- and classical (DYZ1/DYZ3) satellite Y-specific probes did not identify the marker as a Y. Case 2 was a fetus which had a de novo translocation 46,XX,t(3;11)(q26.3;q21) by amniocentesis and confirmed by UBS. FISH for the number 3 and 11 chromosomes confirmed this rearrangement. The parents were advised of the risk associated with a de novo balanced translocation. The possible prognosis for these two different fetuses was not changed by the FISH analysis. FISH, while helpful, is only one aspect of the studies done to provide more accurate genetic counseling to parents; the pregnancy/family history, fetal ultrasound, other possible prenatal studies and pregnancy outcome from perspective studies compose other important aspects that are not mutually exclusive.

  16. Haemophilia: strategies for carrier detection and prenatal diagnosis.

    PubMed Central

    Peake, I. R.; Lillicrap, D. P.; Boulyjenkov, V.; Briet, E.; Chan, V.; Ginter, E. K.; Kraus, E. M.; Ljung, R.; Mannucci, P. M.; Nicolaides, K.

    1993-01-01

    In 1977 WHO published in the Bulletin a Memorandum on Methods for the Detection of Haemophilia Carriers. This was produced following a WHO/WFH (World Federation of Haemophilia) Meeting of Investigators in Geneva in November 1976, and has served as a valuable reference article on the genetics of haemophilia. The analyses discussed were based on phenotypic assessment, which, at that time, was the only procedure available. The molecular biology revolution in genetics during the 1980s made enormous contributions to our understanding of the molecular basis of the haemophilias and now permits precise carrier detection and prenatal diagnosis. WHO and WFH held a joint meeting on this subject in February 1992 in Geneva. This article is the result of these discussions. PMID:8324863

  17. Diagnosis and Management of Behavioral Variant Frontotemporal Dementia

    PubMed Central

    Pressman, Peter; Miller, Bruce L

    2014-01-01

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

  18. The Diagnosis of Mitochondrial Diseases

    E-print Network

    Qian, Ning

    Eric A. Schon, PhD Lewis P. Rowland Professor of Neurology and Genetics & Development H. Houston Merritt Center Peter L. Nagy, M.D., PhD Assistant Professor of Pathology and Cell Biology Kurenai Tanji

  19. Spinocerebellar ataxia type 3/Machado-Joseph disease manifested as spastic paraplegia: A clinical and genetic study

    PubMed Central

    SONG, YANMIN; LIU, YUNHAI; ZHANG, NING; LONG, LILI

    2015-01-01

    The aim of the present study was to conduct a familial investigation and provide a genetic diagnosis to a family presenting with spastic paraplegia and clinically diagnosed with hereditary spastic paraplegia (HSP). Blood samples were obtained from the family, and mutations in the gene causing spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease (MJD), known as MJD1, were analyzed using the polymerase chain reaction, 8% denaturing polyacrylamide gel electrophoresis, and T-vector ligation and sequencing. The trinucleotide repeat number of the mutant allele was 80, leading to a genetic diagnosis of SCA3/MJD. This suggests that patients with SCA3/MJD characteristically present with typical spastic paraplegia without evident manifestations of ataxia. For those families with HSP involving the nervous system and showing genetic anticipation, an MJD1 genetic diagnosis should be considered to assist in clinical diagnosis of HSP. PMID:25574208

  20. Molecular diagnosis of inherited disorders: lessons from hemoglobinopathies.

    PubMed

    Patrinos, George P; Kollia, Panagoula; Papadakis, Manoussos N

    2005-11-01

    Hemoglobinopathies constitute a major health problem worldwide, with a high carrier frequency, particularly in certain regions where malaria has been endemic. These disorders are characterized by a vast clinical and hematological phenotypic heterogeneity. Over 1,200 different genetic alterations that affect the DNA sequence of the human alpha-like (HBZ, HBA2, HBA1, and HBQ1) and beta-like (HBE1, HBG2, HBG1, HBD, and HBB) globin genes are mainly responsible for the observed clinical heterogeneity. These mutations, together with detailed information about the resulting phenotype, are documented in the globin locus-specific HbVar database. Family studies and comprehensive hematological analyses provide useful insights for accurately diagnosing thalassemia at the DNA level. For this purpose, numerous techniques can provide accurate, rapid, and cost-effective identification of the underlying genetic defect in affected individuals. The aim of this article is to review the diverse methodological and technical platforms available for the molecular diagnosis of inherited disorders, using thalassemia and hemoglobinopathies as a model. This article also attempts to shed light on issues closely related to thalassemia diagnostics, such as prenatal and preimplantation genetic diagnoses and genetic counseling, for better-quality disease management. PMID:16138310

  1. Diagnosis and evaluation of acne.

    PubMed

    Eichenfield, Lawrence F; Fowler, Joseph F; Friedlander, Sheila F; Levy, Moise L; Webster, Guy F

    2010-06-01

    The diagnosis of acne usually can be made on the basis of a history and physical examination. The differential diagnosis includes a variety of possible causes and differs according to age group (mid-childhood, 1-7 years of age; pre-, peri-, and early pubertal, 8-11 years of age; pubertal/postpubertal, >or=12 years of age). The presentation of acne in adolescents tends to include both noninflammatory and inflammatory lesions, whereas in younger patients noninflammatory comedones are typical. Keratosis pilaris affecting the cheeks sometimes may be confused with early acne vulgaris. Screening tests, particularly bone age, may be considered to support the clinical diagnosis in younger children. Further testing usually is not indicated unless patients show signs of virilization. PMID:20610307

  2. [Asperger syndrome - a fashionable diagnosis?].

    PubMed

    Haker, Helene

    2014-10-01

    The Asperger Syndrome is - in contrast to early childhood autism - a disorder at the lighter end of the autism spectrum. Although first described in 1943, it was included in the ICD-10 not before 1992. The knowledge about this lighter autistic disorder spread only slowly. The increasing prevalence rates can be explained by the increased knowledge about this disorder and the growing clinical experience. In contrast to the public that gives repeated medial attention to it, and to would-be affected who seem to see an attractive excuse for social problems in an Asperger diagnosis, many psychiatrists appear cautious to state a diagnosis with which they are not familiar and which is discredited as a fashionable diagnosis. PMID:25270748

  3. [The diagnosis of frontotemporal dementia].

    PubMed

    Benke, Th; Donnemiller, E

    2002-05-01

    Frontotemporal Lobar Degeneration (FTDL) is a neurodegenerative disorder which is predominantly characterized by changes in behaviour and loss of cognitive abilities. Three major clinical syndromes have been identified, Frontotemporal dementia (FTD), in which changes in social behaviour predominate, Semantic Dementia (SD) which is characterized by a loss of semantic knowledge, and Primary Progressive Aphasia (PPA), a disorder of phonological and syntactic aspects of language. All subtypes of FTLD have insiduous onset and stepwise progression. The present review lists the clinical symptoms and main findings of the three FTLD-subtypes, and discusses the difficulties of their diagnosis and differential diagnosis. The diagnosis of FTLD is based on the clinical consensus criteria of the Lund and Manchester groups, neuroradiological and neuropsychological investigations. PMID:12007075

  4. Diagnosis of alcoholic liver disease

    PubMed Central

    Torruellas, Cara; French, Samuel W; Medici, Valentina

    2014-01-01

    Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential. PMID:25206273

  5. Advances in the diagnosis of endemic treponematoses: yaws, bejel, and pinta.

    PubMed

    Mitjà, Oriol; Šmajs, David; Bassat, Quique

    2013-01-01

    Improved understanding of the differential diagnosis of endemic treponematoses is needed to inform clinical practice and to ensure the best outcome for a new global initiative for the eradication of yaws, bejel, and pinta. Traditionally, the human treponematoses have been differentiated based upon their clinical manifestations and epidemiologic characteristics because the etiologic agents are indistinguishable in the laboratory. Serological tests are still considered standard laboratory methods for the diagnosis of endemic treponematoses and new rapid point-of-care treponemal tests have become available which are extremely useful in low-resource settings. In the past ten years, there has been an increasing effort to apply polymerase chain reaction to treponematoses and whole genome fingerprinting techniques have identified genetic signatures that can differentiate the existing treponemal strains; however, definitive diagnosis is also hampered by widespread unavailability of molecular diagnostics. We review the dilemmas in the diagnosis of endemic treponematoses, and advances in the discovery of new diagnostic tools. PMID:24205410

  6. Prenatal ultrasound diagnosis of clubfoot.

    PubMed

    Burgan, H E; Furness, M E; Foster, B K

    1999-01-01

    Prenatal ultrasound diagnosis of clubfoot is increasing. Of 103 patients with clubfoot diagnosed at birth, 26 (25.2%) positive prenatal scans were identified with the earliest diagnosis being made at 15 weeks. A questionnaire assessment indicated that 17 (65.4%) deemed that the explanation of the baby's condition was clear. With an increasing incidence of antenatal detection, it is suggested that parents require adequate antenatal counseling by a specialist in the area of clubfoot to improve the understanding of the natural history and treatment of this condition. PMID:9890279

  7. Psychosis in children: diagnosis and treatment

    PubMed Central

    Courvoisie, Helen; Labellarte, Michael J.; Riddle, Mark A.

    2001-01-01

    The diagnosis of childhood psychosis raises a host of unresolved problems, despite the Diagnostic and Statistical Manual Of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) giving identical symptoms and definitions for children, adolescents, and adults. The fantasy lives of children, and issues of developing language and cognition (including retardation), all impair diagnostic accuracy, particularly when differentiating between childhood-onset schizophrenia (COS) (?12 years), bipolar affective disorder, major depressive disorder, and even obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: the catch-all classification, psychosis not otherwise specified (PNOS), is always available for conundra that prove unsolvable. Typical if nonpathognomonic features include neurocognitive difficulties. Multiple screening instruments and specialized versions of semistructured diagnostic interviews are available. Although smooth-pursuit eye-tracking movements may prove a genetic marker for COS, etiologies are likely to be oligogenetic rather than related to a single gene. No specific biological markers or neuroimages have been identified. As such, psychoses may be indicative of a more general pattern of brain dysfunction. Drug treatments are largely based on the adult literature because of a dearth of controlled data below age 18. There are still no rigorous studies of psychosocial treatments and psychotherapy specific to childhood psychosis. PMID:22033588

  8. Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment.

    PubMed

    Engel, Andrew G; Shen, Xin-Ming; Selcen, Duygu; Sine, Steven M

    2015-04-01

    The congenital myasthenic syndromes (CMS) are a diverse group of genetic disorders caused by abnormal signal transmission at the motor endplate, a special synaptic contact between motor axons and each skeletal muscle fibre. Most CMS stem from molecular defects in the muscle nicotinic acetylcholine receptor, but they can also be caused by mutations in presynaptic proteins, mutations in proteins associated with the synaptic basal lamina, defects in endplate development and maintenance, or defects in protein glycosylation. The specific diagnosis of some CMS can sometimes be reached by phenotypic clues pointing to the mutated gene. In the absence of such clues, exome sequencing is a useful technique for finding the disease gene. Greater understanding of the mechanisms of CMS have been obtained from structural and electrophysiological studies of the endplate, and from biochemical studies. Present therapies for the CMS include cholinergic agonists, long-lived open-channel blockers of the acetylcholine receptor ion channel, and adrenergic agonists. Although most CMS are treatable, caution should be exercised as some drugs that are beneficial in one syndrome can be detrimental in another. PMID:25792100

  9. [Borderline personality disorders: diagnosis and treatment].

    PubMed

    Allilaire, Jean-François

    2012-10-01

    Borderline personality disorders are complex clinical states with highly polymorphic symptoms and signs, leading to delays in their diagnosis and treatment. All international classifications emphasize certain clinical criteria such as unstable identity and interpersonal relationships, feelings of emptiness or boredom, and pathological impulsiveness. The prevalence is about 2%, with a female-male sex ratio of 2 or 3 to 1. Both adolescents and adults may be affected There is a high risk of suicide, addictive behaviors, eating disorders, and criminality. These individuals frequently have a history of trauma in early childhood, such as separation, loss, physical or sexual abuse, or affective privation. Subjective signs and symptoms are particularly important in the diagnostic and therapeutic evaluation, and this requires an empathic and subtle approach. Standardized and semi-structured interviews may help to identify comorbidities such as thymic disorders, anxiety, addiction, eating disorders, and, in some cases, psychotic symptoms. The psychiatric bio-psycho-social model takes into account multiple pathogenic factors, such as trauma during early development, temperamental instability and other emotional disorders, as well as psychosocial, neurobiological (5HT etc.) and genetic vulnerabilities. Treatment requires optimal integration of psychotherapeutic and pharmacotherapeutic approaches. Emergency intervention must be available in case of delirious or suicidal behavior The clinical course is often lengthy and complex, but outcome may be favorable, provided the principal risk--suicide--is correctly managed, PMID:23815019

  10. Chronic fatigue syndrome: diagnosis and treatment.

    PubMed

    Yancey, Joseph R; Thomas, Sarah M

    2012-10-15

    Chronic fatigue syndrome is characterized by debilitating fatigue that is not relieved with rest and is associated with physical symptoms. The Centers for Disease Control and Prevention criteria for chronic fatigue syndrome include severe fatigue lasting longer than six months, as well as presence of at least four of the following physical symptoms: postexertional malaise; unrefreshing sleep; impaired memory or concentration; muscle pain; polyarthralgia; sore throat; tender lymph nodes; or new headaches. It is a clinical diagnosis that can be made only when other disease processes are excluded. The etiology of chronic fatigue syndrome is unclear, is likely complex, and may involve dysfunction of the immune or adrenal systems, an association with certain genetic markers, or a history of childhood trauma. Persons with chronic fatigue syndrome should be evaluated for concurrent depression, pain, and sleep disturbances. Treatment options include cognitive behavior therapy and graded exercise therapy, both of which have been shown to moderately improve fatigue levels, work and social adjustment, anxiety, and postexertional malaise. No pharmacologic or alternative medicine therapies have been proven effective. PMID:23062157

  11. Avoiding transgenerational risks of mitochondrial DNA disorders: a morally acceptable reason for sex selection?

    PubMed

    Bredenoord, Annelien L; Dondorp, Wybo; Pennings, Guido; De Wert, Guido

    2010-06-01

    In this article, we discuss sex selection not intended to help a couple avoid having a child with a severe genetic disorder, but to avoid possible health risks further along the line of generations. Sex selection may be put to this use in the context of preventing mitochondrial DNA disorders by means of preimplantation genetic diagnosis (PGD) and possibly in the future also through nuclear transfer (NT; also known as mitochondrial gene replacement). A relevant analogy can be found in the context of PGD for X-linked diseases, where sex selection against healthy female carrier embryos would have the same 2-fold purpose of (i) avoiding difficult reproductive decisions for the future child and (ii) avoiding transmission of the mutation to a possible third generation. Because sex selection would still be done for reasons of health, this application should not give rise to the moral concerns associated with sex selection for non-medical reasons. However, the proportionality of adding the relevant procedures to PGD or NT is a relevant concern. We discuss post- and preconceptional sex selection strategies. We conclude that if PGD is already part of the procedure, either as the central technology or as a back-up test after NT, preferentially transferring male embryos could in principle be a morally acceptable way of reducing possible burdens and risks. To start an IVF/PGD-cycle especially for this purpose would be disproportional. The alternative approach of preconceptional sex selection may be morally justified as a means to increase the chances of obtaining male embryos. PMID:20364025

  12. [Pervasive developmental disorders. Clinical and genetics aspects].

    PubMed

    Ruggieri, Victor; Arberas, Claudia

    2007-01-01

    Pervasive developmental disorders (PDD) encompass a heterogeneous group of children with deficits of verbal and non-verbal language, social communication, and with a restricted repertoire of activities or repetitive behaviours. The frequency in general population is considered 27.5/10,000. In this study, we analyzed the clinical and genetic aspects of Autism, Asperger Syndrome, PDD Not Otherwise Specified, Rett Syndrome and Childhood Disintegrative Disorder. We analyzed clinical, behavioural and neuropsychological features. We revised different medical genetics associated conditions and divided the genetics aspects of pervasive developmental disorders into two groups: Syndromic forms (around 20%) and non syndromic forms (currently proposed to be 80%). The early recognition of pervasive developmental disorders and the diagnosis of specific associated syndromes allow early therapy, correct genetic counselling, and follow up anticipating possible complications related to the entity. Finally, although the genetic bases of autism have not yet been identified, the following candidate genes have been proposed: 15q, 2q, 17q, 7q, 12q, and X related genes, among others; which are analyzed in this study and will allow a better understanding of these disorders in the future. PMID:18422083

  13. Attitudes of deaf individuals towards genetic testing.

    PubMed

    Taneja, Patricia Rubal; Pandya, Arti; Foley, Debra L; Nicely, Lauren Vanner; Arnos, Kathleen S

    2004-09-15

    Recent advances have made molecular genetic testing for several forms of deafness more widely available. Previous studies have examined the attitudes of the deaf towards genetic testing, including prenatal diagnosis. This study examines the attitudes of deaf college students towards universal newborn hearing screening, including molecular testing for specific forms of deafness, as well as the utilization of genetic test results for mate selection. We found that there may be differences in the attitudes of deaf individuals who associate closely with the deaf community (DC), and those who have equal involvement with both the deaf and hearing communities (EIC). The majority perceived newborn hearing screening for deafness to be helpful. However, more members of the EIC than the DC groups support newborn testing for genes for deafness. While there was reported interest in using genetic testing for partner selection, most participants reported they would not be interested in selecting a partner to have children with a specific hearing status. The results of this study point out important differences that genetic professionals should be aware of when counseling deaf individuals. PMID:15368489

  14. Genetics Home Reference: Cranioectodermal dysplasia

    MedlinePLUS

    ... dysplasia? CED Sensenbrenner syndrome For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes ...

  15. Genetics Home Reference: Otospondylomegaepiphyseal dysplasia

    MedlinePLUS

    ... Oto-spondylo-megaepiphyseal dysplasia For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes ...

  16. Genetics Home Reference: Lynch syndrome

    MedlinePLUS

    ... nonpolyposis colorectal neoplasms HNPCC For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes ...

  17. Genetics Home Reference: Essential pentosuria

    MedlinePLUS

    ... pentosuria xylitol dehydrogenase deficiency For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes ...

  18. Genetics Home Reference: Farber lipogranulomatosis

    MedlinePLUS

    ... lipogranulomatosis Farber-Uzman syndrome For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes ...

  19. Genetics Home Reference: Alport syndrome

    MedlinePLUS

    ... interstitial pyelonephritis hereditary nephritis For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes ...

  20. Karyotypes to Predict Genetic Disorders- A Lesson on Genetics

    NSDL National Science Digital Library

    Karen Walton (Chapin High School)

    2008-08-01

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