These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

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

Microsoft Academic Search

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

Andrea L Kalfoglou; Joan Scott; Kathy Hudson

2005-01-01

2

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

PubMed

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

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

1999-12-01

3

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

PubMed Central

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

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

2010-01-01

4

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

SciTech Connect

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

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

1994-09-01

5

Preimplantation genetic diagnosis (PGD) in Europe: diversity of legislation a challenge to the community and its citizens.  

PubMed

Preimplantation genetic diagnosis (PGD) aims to safeguard the reproductive confidence of couples who have an increased risk of having a child with a serious hereditary disease. Non-directive genetic counselling is an essential part of PGD. Lately, performance of PGD for some new and non-medical indications, such as selecting for a tissue-matching embryo for a saviour sibling, or sex-selection for family-balancing, has raised ethical concerns. Who decides when to perform PGD, and for which conditions? The European member states have very diverse regulation on PGD. Some countries totally ban PGD, while the others keep close track of the new applications. The people in need of PGD seek it in the other member states. These cross-border treatments cause psychological stress and pose many so far unresolved legal questions. The individuals need more information about all the aspects of PGD. This article analyses contemporary indications for PGD in Europe and relevant ethical discussion, and second, shows the diversity in regulation and reflects the consequences thereof. PMID:17639853

Soini, S

2007-06-01

6

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

Microsoft Academic Search

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

Andrea L Kalfoglou; Joan Scott; Kathy Hudson

7

The Ethics of Preimplantation Genetic Diagnosis  

NSDL National Science Digital Library

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

Foundation, Wgbh E.

2012-03-30

8

Clinical applications of fetal sex determination in maternal blood in a preimplantation genetic diagnosis centre  

Microsoft Academic Search

BACKGROUND: Couples with a risk of transmitting X-linked diseases who are included in a preimplantation genetic diagnosis (PGD) programme need early and rapid fetal sex determination in two situations. The first situation is for the control of embryo sexing after PGD and the second situation is for those couples having a spontaneous pregnancy before the start of their PGD cycle.

Gerard Tachdjian; Nelly Frydman; Francois Audibert; Pierre Ray; Violaine Kerbrat

9

Social representations of stem cell research and preimplantation genetic diagnosis  

Microsoft Academic Search

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

BA Jones; CA McMahon

2003-01-01

10

Successful polar body-based preimplantation genetic diagnosis for achondroplasia  

Microsoft Academic Search

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

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

2008-01-01

11

Preimplantation genetic diagnosis for achondroplasia: genetics and gynaecological limits and difficulties  

Microsoft Academic Search

BACKGROUND: We report the first attempts at preimplantation genetic diagnosis (PGD) and IVF and their accompanying difficulties for achondroplasia (ACH) patients. METHODS: A PGD test was developed using fluorescent single cell PCR on lymphoblasts from patients and controls and from blastomeres from surplus IVF embryos. A specific digestion control based on the use of two fluorochromes was elaborated. Ovarian stimulation

Celine Moutou; Catherine Rongieres; Karima Bettahar-Lebugle; Nathalie Gardes; Christophe Philippe; Stephane Viville

2003-01-01

12

Preimplantation genetic diagnosis (embryo screening) for enlarged vestibular aqueduct due to SLC26A4 mutation.  

PubMed

Preimplantation genetic diagnosis (PGD) is used to analyze embryos genetically before their transfer into the uterus. For families with genetic diseases, PGD offers a chance to have an unaffected child, without facing termination of pregnancy. Although PGD has been performed for many monogenic disorders, such as cystic fibrosis and beta-thalassemia, the application of PGD to hereditary hearing impairment has not been explored. In the present study, we reported the development and application of PGD protocols to address enlarged vestibular aqueduct (EVA), which is a common type of hereditary hearing impairment associated with mutations in the SLC26A4 gene. The family requesting PGD had a history of EVA, segregating the SLC26A4 c.919-2A-->G mutation. In short, the PGD process was composed of two steps: the development of a single-cell testing protocol and clinical PGD cycles (i.e., selection and implantation of unaffected embryos using the single-cell testing protocol). First, protocols for genetic testing in a single cell were established for the c.919-2A-->G mutation using GenomiPhi technology and primer extension mini-sequencing. These protocols were validated on single lymphocytes collected from both parents and their affected child. Two clinical PGD cycles were then performed for the parents, with the second cycle successfully leading to a singleton pregnancy. The baby was homozygous for the wild-type SLC26A4 allele and revealed a normal audiological phenotype after birth. To our knowledge, this is the first report in the literature describing successful PGD in families with genetic hearing impairment. In our opinion, the application of PGD in the field of hereditary hearing impairment involves fewer ethical controversies than other novel applications of PGD and traditional indications for PGD for other monogenic diseases. Therefore, the approach demonstrated in the present study can also be used in a large number of families with other types of hereditary hearing impairment. PMID:20160438

Wu, Chen-Chi; Lin, Shin-Yu; Su, Yi-Nin; Fang, Mei-Ya; Chen, Shee-Uan; Hsu, Chuan-Jen

2010-01-01

13

Clinical management of in vitro fertilization with preimplantation genetic diagnosis.  

PubMed

Patients who undergo in vitro fertilization (IVF) because of preimplantation genetic diagnosis (PGD) require different clinical management than those who come in because of infertility alone. PGD adds a "fourth dimension" to the emotional aspect of a patients' assisted reproductive technology treatment. It significantly decreases the number of embryos available for transfer by 25 to 81%, and therefore ovarian stimulation for IVF with PGD should be tailored individually, taking into account patients' safety and estimated ovarian reserve. Recent studies showed that with increased number of oocytes retrieved, the higher the chance to have an embryo transfer and normal cryopreserved blastocysts. With adequate ovarian stimulation, there is no cutoff for the numbers of oocytes/embryos needed to start PGD with, especially for younger patients. Patient-friendly protocols, such as those based on gonadotropin-releasing hormone antagonist and vaginal progesterone support may be used. Elective single embryo transfer and blastocysts cryopreservation to avoid multiple pregnancies may be offered with PGD. The benefit of adding preimplantation genetic screening to IVF treatment is still controversial, and evidence-based data on 24-chromosome testing of polar bodies or trophectoderm is needed before it may be implemented into routine patient care.This review discusses the clinical management of IVF with PGD based on the best available data and my personal clinical experience as a reproductive specialist with >1000 IVF/intracytoplasmic sperm injection-PGD cycles. The information provided here will assist reproductive specialists, nurses, geneticists, genetic counselors, and embryologists to better counsel and treat couples who wish to conceive with a healthy child through IVF with PGD. It is time for PGD to be viewed as a modern modality of preventive medicine. As such, it should be incorporated into national health-care systems and be covered by medical insurance. PMID:22723012

Tur-Kaspa, Ilan

2012-08-01

14

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

PubMed

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

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

2008-01-01

15

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

PubMed

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

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

2015-01-01

16

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

PubMed Central

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

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

2014-01-01

17

Clinical guidelines for IVF with PGD for HLA matching.  

PubMed

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

Tur-Kaspa, Ilan; Jeelani, Roohi

2015-02-01

18

Preimplantation genetic diagnosis and rational choice under risk or uncertainty.  

PubMed

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

Zuradzki, Tomasz

2014-11-01

19

Saviour embryos? Preimplantation genetic diagnosis as a therapeutic technology.  

PubMed

The creation of 'saviour siblings' is one of the most controversial uses of preimplantation genetic diagnosis (PGD). This paper outlines and invites ethical discussion of an extension of this technology, namely, the creation of 'saviour embryos' to serve as a source of stem cells to be used in potentially life-saving therapy for an existing child. A number of analogies between this hypothetical use of PGD and existing uses of IVF are offered and, in addition, between saviour embryos and proposed therapeutic applications of stem cell technology. The ethical significance of a number of disanalogies between these cases are explored and investigated. While the creation of saviour embryos would involve a significant shift in the rationale for IVF and PGD, it is suggested here that the urgent need of an existing individual should be prioritised over any obligations that might exist in relation to the creation or destruction of human embryos. PMID:20189455

Sparrow, Robert; Cram, David

2010-05-01

20

Human embryos as boundary objects? Some reflections on the biomedical worlds of embryonic stem cells and pre-implantation genetic diagnosis  

Microsoft Academic Search

In this paper we offer some reflections on embryos in the biomedical worlds of embryonic stem cells (ESC) and pre-implantation genetic diagnosis (PGD). We draw upon two ethnographic studies of the social practices of PGD and embryonic stem cell science to examine the notion of boundary objects as an approach for understanding the social construction of embryos. We analyze the

Clare Williams; Steven P. Wainwright; Kathryn Ehrich; Mike Michael

2008-01-01

21

Reiterative changes in the Italian regulation on IVF: the effect on PGD patients' reproductive decisions.  

PubMed

National legislations represent one of the main factors influencing access to assisted reproduction treatment. The Italian situation in the last decade is an example of how the treatment of patients for preimplantation genetic diagnosis (PGD) was more dependent on regulators than on medical choices. This report analysed how the changes in Italian regulation affected the number of PGD referrals to this study centre, as well as their decision to opt for cross-border reproductive care (CBRC). The analysis showed that during the period in which PGD was actually not performed because of the restriction imposed by the Italian law on IVF (from 24 February 2004 to 7 May 2009) there was a significant decrease in the number of referrals asking for PGD (2.5% of total referrals) compared with the previous years (3.3%; P < 0.025) and following years when PGD was legalized (5.1%; P < 0.001). The number of couples opting for CBRC had an opposite trend, reaching a maximum when PGD was banned from Italian centres (55 couples), whereas after the readmission of PGD, only eight couples went abroad for treatment. Concomitantly, since May 2009, the proportion of couples performing a PGD cycle in this centre has constantly increased. PMID:24268726

Gianaroli, Luca; Crivello, Anna Maria; Stanghellini, Ilaria; Ferraretti, Anna Pia; Tabanelli, Carla; Magli, Maria Cristina

2014-01-01

22

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

Microsoft Academic Search

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

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

1999-01-01

23

Selecting "saviour siblings": reconsidering the regulation in Australia of pre-implantation genetic diagnosis in conjunction with tissue typing.  

PubMed

In recent years, pre-implantation genetic diagnosis (PGD) has been developed to enable the selection of a tissue type matched "saviour sibling" for a sick child. This article examines the current regulatory framework governing PGD in Australia. The availability of PGD in Australia to create a saviour sibling depends on the regulation of ART services by each State and Territory. The limitations on the use of PGD vary throughout Australia, according to the level of regulation of ART in each jurisdiction. This article considers the limitations on the use of PGD for tissue typing in Australia and argues that some of these should be removed for a more consistent national approach. In particular, the focus in ART legislation on the "paramount interests" of the child to be born is inappropriate for the application of tissue typing, which necessarily involves the interests of other family members. PMID:17571785

Taylor-Sands, Michelle

2007-05-01

24

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

PubMed Central

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

Theodosiou, Anastasia A.; Johnson, Martin H.

2011-01-01

25

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

PubMed

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

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

2011-01-01

26

Peutz–Jeghers syndrome and family planning: the attitude towards prenatal diagnosis and pre-implantation genetic diagnosis  

Microsoft Academic Search

Peutz–Jeghers syndrome (PJS) is a hereditary disorder caused by LKB1 gene mutations, and is associated with considerable morbidity and decreased life expectancy. This study was conducted to assess the attitude of PJS patients towards family planning, prenatal diagnosis (PND) and pregnancy termination, and pre-implantation genetic diagnosis (PGD). In a cross-sectional study, 61 adult PJS patients were asked to complete a

Margot G F van Lier; Susanne E Korsse; Elisabeth M H Mathus-Vliegen; Ernst J Kuipers; Ans M W van den Ouweland; Kathleen Vanheusden; Monique E van Leerdam; Anja Wagner

2012-01-01

27

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

PubMed

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

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

2014-04-01

28

Increasing the denaturation temperature during the first cycles of amplification reduced allele dropout from single cells for preimplantation genetic diagnosis  

Microsoft Academic Search

Single cell polymerase chain reaction (PCR) for preimplantation genetic diagnosis (PGD) needs to be highly efficient and accurate. In some single cells from human embryos presumed to be heterozygous for the AF508 deletion causing cystic fibrosis (CF), we recently observed random amplification failure of one of the two parental alleles following nested PCR. To investigate allele dropout (ADO), we have

Pierre F. Ray; Alan H. Handyside

1996-01-01

29

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

PubMed Central

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

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

2012-01-01

30

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

PubMed Central

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

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

2014-01-01

31

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

PubMed

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

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

2015-02-01

32

Birth of a Healthy Histocompatible Sibling following Preimplantation Genetic Diagnosis for Chronic Granulomatous Disease at the Blastocyst Stage Coupled to HLA Typing  

Microsoft Academic Search

Objective: To perform preimplantation genetic diagnosis (PGD) for chronic granulomatous disease with simultaneous HLA typing in a family case with an affected male child, with the aim of selecting unaffected and HLA-matched embryos to act as donors for hematopoietic stem cell transplantation from umbilical cord blood. Methods: A flexible, indirect HLA haplotyping protocol, based on single-cell multiplex PCR analysis of

Constantinos G. Pangalos; Birgitta Hagnefelt; Georgia Kokkali; Konstantinos Pantos; Christopher P. Konialis

2008-01-01

33

The experience of 3 years of external quality assessment of preimplantation genetic diagnosis for cystic fibrosis  

PubMed Central

Preimplantation genetic diagnosis (PGD) was first performed over 20 years ago and has become an accepted part of genetic testing and assisted reproduction worldwide. The techniques and protocols necessary to carry out genetic testing at the single-cell level can be difficult to master and have been developed independently by the laboratories worldwide offering preimplantation testing. These factors indicated the need for an external quality assessment (EQA) scheme for monogenic disease PGD. Toward this end, the European Society for Human Reproduction and Embryology came together with United Kingdom National External Quality Assessment Services for Molecular Genetics, to create a pilot EQA scheme followed by practical EQA schemes for all interested parties. Here, we detail the development of the pilot scheme as well as development and findings from the practical (clinical) schemes that have followed. Results were generally acceptable and there was marked improvement in results and laboratory scores for those labs that participated in multiple schemes. Data from the first three schemes indicate that the EQA scheme is working as planned and has helped laboratories improve their techniques and result reporting. The EQA scheme for monogenic PGD will continue to be developed to offer assessment for other monogenic disorders. PMID:23150080

Deans, Zandra; Fiorentino, Francesco; Biricik, Anil; Traeger-Synodinos, Joanne; Moutou, Céline; De Rycke, Martine; Renwick, Pamela; SenGupta, Sioban; Goossens, Veerle; Harton, Gary

2013-01-01

34

Preimplantation genetic diagnosis for gender selection in the United States  

SciTech Connect

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

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

2009-08-20

35

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

PubMed

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

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

36

Successful PGD for late infantile neuronal ceroid lipofuscinosis achieved by combined chromosome and TPP1 gene analysis.  

PubMed

Late infantile neuronal ceroid lipofuscinosis (NCL-2) is a severe debilitating autosomal recessive disease caused by mutations in TPP1. There are no effective treatments, resulting in early childhood death. A couple with two affected children presented for reproductive genetic counselling and chose to undertake IVF and preimplantation genetic diagnosis (PGD) to avoid the possibility of another affected child. However, DNA testing revealed only one mutation in the proband inherited from mother. Linkage analysis identified five informative linked short tandem repeat markers to aid the genetic diagnosis. Following IVF, five cleavage-stage embryos were biopsied and blastomeres were first subjected to whole-genome amplification, then a series of down-stream molecular genetic analyses to diagnose TPP1 genotype and finally array comparative genomic hybridization (CGH) to assess the chromosomal ploidy of each embryo. Two unaffected euploid embryos were identified for transfer. One was transferred on day 5 resulting in an ongoing pregnancy. Confirmatory prenatal diagnosis by amniocentesis showed concordance of the embryo and fetal diagnosis. As far as is known, this is the first successful report of PGD for NCL-2 using double-factor PGD with simultaneous single-gene testing and array CGH to identify an unaffected and chromosomally normal embryo for transfer. PMID:23768618

Shen, Jiandong; Cram, David Stephen; Wu, Wei; Cai, Lingbo; Yang, Xiaoyu; Sun, Xueping; Cui, Yugui; Liu, Jiayin

2013-08-01

37

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

PubMed Central

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

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

2013-01-01

38

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

PubMed

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

Edwards, R G

2004-08-01

39

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

Microsoft Academic Search

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

RG Edwards

2004-01-01

40

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

PubMed

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

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

2014-07-01

41

Diagnosis and new treatments in genetic neuropathies  

Microsoft Academic Search

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

M M Reilly; M E Shy

2009-01-01

42

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

PubMed Central

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

Ehrich, Kathryn; Williams, Clare; Farsides, Bobbie

2008-01-01

43

Singling out genetic disorders and disease  

PubMed Central

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

2010-01-01

44

Genetic Issues in the Diagnosis of Dystonias  

PubMed Central

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

Petrucci, Simona; Valente, Enza Maria

2013-01-01

45

Diagnosis of genetic defects by chromosomal analysis.  

PubMed

Of 901 karyotypes performed over a period of 4 years, genetic anomalies were detected in 162 cases. Down's syndrome (trisomy 21) was the most common (168.8%) genetic disorder followed by Turner's syndrome, Philadelphia chromosome, Klinefelter's syndrome, Edward's syndrome (trisomy 18) and Patau's syndrome (trisomy 13). All the three trisomies were detected very early in life. Mean age at the time of diagnosis for Turner's syndrome was 13.3 years, allowing a timely hormone replacement therapy to improve secondary sexual characters. Patients with Klinefelter's syndrome were diagnosed late (mean age 23.6 years), which greatly reduced their chances of an effective therapy to improve the clinical and social outcome. PMID:8920609

Ghani, F; Maniar, S; Khilji, Z; Azim, M; Khurshid, M

1995-11-01

46

Genetic analysis for early diagnosis of otorhinolaryngeal diseases  

PubMed Central

Familiarity with the concepts and methods of human genetics is important in order to be able to perform genetic analysis. The grade of predictability of a genetic disease is partly given by formal genetics but also depends on the importance of the mutated gene for the phenotype. Possibilities for genetic analysis range from differential diagnosis to predictive diagnosis to prenatal diagnosis. After initial consultation in which the physician fully explains the procedure to the patient, it is mandatory that the patient give his full consent. This article summarises and evaluates current knowledge about genetic analysis of important otorhinolaryngeal diseases, including hereditary hearing disabilities, olfactory malfunction, hereditary tumorous diseases, hereditary syndromes and dysplasias. In addition, this article discusses genetic diseases that affect voice and speech, highlights the relevance of human genetic consultation and discusses the importance of embedding genetic analysis in medicine in general. PMID:22073089

Propping, Peter

2010-01-01

47

Preimplantation diagnosis to create 'saviour siblings': a critical discussion of the current and future legal frameworks in South Africa.  

PubMed

Pre-implantation genetic diagnosis (PGD) is a technology used in conjunction with in vitro fertilisation to screen embryos for genetic conditions prior to transfer. It was initially developed to screen mutations for severe, irreversible, genetic conditions. Currently, PGD makes it possible to select against more than 100 different genetic conditions. It has been proposed as a method for creating a tissue-matched child who can in turn serve as a compatible stem cell donor to save a sick sibling in need of a stem cell transplant. The advantage of this method is that it provides genetic information before implantation of an embryo into the womb, making it possible to ensure that only tissue-matched embryos are transferred to the uterus. A couple can therefore avoid the difficult choice of either terminating the pregnancy at a later point if the fetus is not a match, or extending their family again in the hope that their next child will be tissue compatible. Many people have expressed disapproval of the use of PGD for this purpose, and it is associated with many conflicting interests including religion, ethics as well as legal regulation. In order to manage these issues some jurisdictions have created legal frameworks to regulate the use of this technology. Many of these are modelled on the UK's Human Fertilisation and Embryology Authority and its guardian legislation. This paper critiques the current and future South African legal framework to establish whether it is able to adequately regulate the use of PGD as well as guard against misuse of the technology. It concludes that changes are required to the future framework in order to ensure that it regulates the circumstances in which PGD may occur and that the Minister of Health should act expediently in finalising draft regulations which will regulate PGD in the future. PMID:22273130

Strode, Ann; Soni, Sheetal

2012-01-01

48

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

Microsoft Academic Search

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

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

1998-01-01

49

[Preimplantation genetic diagnosis in order to choose a saviour sibling].  

PubMed

Preimplantation genetic diagnosis with HLA matching in order to bring about the birth of a saviour sibling is not mere instrumentalisation of the future child, as long as the post natal test is used and the future child will be looked after with the same love and care as if he/she had not been selected as well for the purpose. PMID:16139548

Shenfield, F

2005-10-01

50

Critical Issues for Dentistry: PGD Program Directors Respond.  

ERIC Educational Resources Information Center

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

Atchison, Kathryn A.; Cheffetz, Susan E.

2002-01-01

51

Multiple displacement amplification on single cell and possible PGD applications  

Microsoft Academic Search

Multiple displacement amplification (MDA) is a technique used in the amplification of very low amounts of DNA and reported to yield large quantities of high-quality DNA. We used MDA to amplify the whole genome directly from a single cell. The most common techniques used in PGD are PCR and fluorescent in-situ hybridization (FISH). There are many limitations to these techniques

Ali Hellani; Serdar Coskun; Moncef Benkhalifa; Abelghani Tbakhi; Nadia Sakati; Ali Al-Odaib; Pinar Ozand

2004-01-01

52

Genetic imprecision: Diagnosis of possible defects often cannot predict prognosis  

SciTech Connect

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

Lewis, R.

1991-05-01

53

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

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

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

2014-01-01

54

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

SciTech Connect

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

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

1994-09-01

55

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

PubMed Central

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

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

2009-01-01

56

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

PubMed

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

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

2014-05-01

57

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

Microsoft Academic Search

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

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

2008-01-01

58

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

PubMed Central

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

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

2014-01-01

59

6-Phosphogluconate dehydrogenase (PGD) allele phylogeny is incongruent with a recent origin of polyploidization in some North American Sphaeriidae (Mollusca, Bivalvia).  

PubMed

Although polyploidization is rare among bivalve mollusks, recent cytogenetic studies have revealed a remarkable degree of genome amplification (up to 13n) in the freshwater bivalve family Sphaeriidae. We generated single-copy nuclear gene trees in order to test hypotheses addressing the evolutionary origins of sphaeriid genome duplication. Polyploid North American members of three cosmopolitan sphaeriid genera (Sphaerium, Musculium, and Pisidium) were characterized for their expressed allelic repertoire of a 526 nt c-DNA fragment of 6-phosphogluconate dehydrogenase (PGD). Pronounced levels of intra-individual genetic variation were uncovered in most of the polyploid taxa and a minority of alleles showed strong evidence of recombination. Phylogenetic analyses resolved polyploid sphaeriid PGD alleles into two clades (A, B), each of which contained a subsample of intra-individual allelic diversity of the genus Sphaerium. These two clades were also recovered in Musculium, however one (B) is represented here by a single recombinant allele. With the exception of a divergent segment in one putatively recombinant allele, the expressed PGD repertoire of the three Pisidium species investigated was restricted to one of the two clades (A). Major within-clade PGD gene tree branching patterns were congruent with mitochondrial gene tree topologies for these taxa. These results are inconsistent with a pattern of recent independent attainment of a polyploid status by our Sphaerium/Musculium study taxa and indicate that they may share a common genome duplication event predating the Miocene appearance of these two genera in the fossil record. PMID:12383755

Lee, Taehwan; Foighil, Diarmaid O

2002-10-01

60

Prediction of Collapse from PGV and PGD S. Song & T.H. Heaton  

E-print Network

Prediction of Collapse from PGV and PGD S. Song & T.H. Heaton California Institute of Technology, Pasadena, CA, USA SUMMARY: We propose a collapse prediction model described in peak ground velocity (PGV seismic motions; the simulations showed that collapse can be predicted from PGV and PGD. Song and Heaton

Greer, Julia R.

61

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

PubMed Central

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

2012-01-01

62

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

E-print Network

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

Fernandez, Thomas

63

A Genetic Algorithm System to Find Symbolic Rules for Diagnosis of Depression  

Microsoft Academic Search

A machine learning method is proposed for automatically finding psychiatric diagnostic rules. It is proposed that a genetic algorithm (GA) system can find symbolic, easily readable rules that could be used by psychiatric clinicians. Diagnosis of major depressive disorder is considered. A sample of 320 subjects with symptom information and pre-assigned diagnosis is used to train a GA model and

Christopher N. Chapman; Lana Deaton; Angela Harris; Nova Robinson

1999-01-01

64

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

E-print Network

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

Granada, Universidad de

65

Fault diagnosis of turbo-generator based on support vector machine and genetic algorithm  

Microsoft Academic Search

Support vector machine (SVM) can overcome the drawbacks of artificial neural network, which has been widely used for pattern recognition in recent years. In the study, a novel method based on support vector machine and genetic algorithm (GA-SVM) model is adopted to fault diagnosis of turbo-generator, in which genetic algorithm (GA) dynamically optimizes the values of SVM's parameters C and

Shen Xiao-feng; Shen Yu; Guo Lin

2009-01-01

66

Preimplantation genetic testing in the 21st century: uncharted territory.  

PubMed

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

Brezina, Paul R

2013-02-10

67

Molecular diagnosis and genetic counseling for fragile X mental retardation.  

PubMed

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

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

2004-03-01

68

In vitro evaluation of poly(caporlactone) grafted dextran (PGD) nanoparticles with cancer cell.  

PubMed

This study dealt with the preparation and characterization of coumarin-6 loaded poly(caprolactone) grafted dextran (PGD) nanoparticles (NPs) and evaluation of cellular uptake by using human gastric cancer cell line (SNU-638), in vitro. The potential application of these PGD NPs for sustained drug delivery was evaluated by the quantification and localization of the cellular uptake of fluorescent PGD NPs. Coumarin-6 loaded PGD NPs were prepared by a modified oil/water emulsion technique and characterized by various physico-chemical methods such as, laser light scattering for particle size and size distribution, atomic force microscopy (AFM), zeta-potential and spectrofluorometry to identify the release of fluorescent molecules from the NPs. SNU-638 was used to measure the cellular uptake of fluorescent PGD NPs. Confocal laser scanning microscopic images clearly showed the internalization of NPs by the SNU-638 cells. Cell viability was assessed by treating the SNU-638 cells with PGD NPs for 48 h. The results reveal, that these biodegradable polymeric NPs holds promise in biomedical field as a carrier. PMID:18040758

Prabu, P; Chaudhari, Atul A; Aryal, Santosh; Dharmaraj, N; Park, S Y; Kim, W D; Kim, H Y

2008-05-01

69

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

PubMed

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

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

70

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

PubMed Central

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

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

2013-01-01

71

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

PubMed Central

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

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

2014-01-01

72

Ethical and legal aspects of noninvasive prenatal genetic diagnosis.  

PubMed

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

Dickens, Bernard M

2014-02-01

73

[Inflammatory myopathies, autoimmune necrotizing myopathies and adult-onset genetic myopathies: differential diagnosis].  

PubMed

The inflammatory myopathies are an important and treatable group of disorders. The diagnostic criteria and the classifications are complex and subject to debate. Furthermore, there is clinical and histopathological overlap between the features of inflammatory myopathies and those of adult-onset genetic myopathies. In this review, we will discuss the two more common pitfalls in inflammatory myopathies diagnosis: firstly, the misdiagnosis between different types of inflammatory myopathies and uncommon myopathies; secondly, the confusion between inflammatory myopathies and genetic myopathies. Among the group of limb-girdle dystrophies, dysferlinopathies are the more common confounding myopathies. An accurate diagnosis is essential for an optimal management in patients with myopathies. PMID:22204923

Dimitri, D; Eymard, B

2012-03-01

74

Yin-Yang regulation of prostaglandins and nitric oxide by PGD2 in human arthritis: reversal by celecoxib.  

PubMed

The role of PGD2 has been recognized in allergy, innate immunity and inflammation. Western blot analysis identified 21 kDa lipocalin (L)-prostaglandin D2 (PGD2) synthase (S) in human osteoarthritis (OA)-affected cartilage, whose expression was increased by IL-1? and TNF?. Similarly, PGD2 was spontaneously released by human OA-affected cartilage (and upregulated by IL-?) in ex vivo conditions and could be inhibited by indomethacin. Addition of PGD2 to human OA-affected cartilage significantly increased accumulation of PGE2, PGF1?, PGF2?, TXB2, but inhibited LTB4 and nitric oxide (NO) accumulation. Similarly, PGD2 (but not 13,14-dihydro-15-keto PGD2) augmented IL-1? induced PGE2 but inhibited IL-? induced nitric oxide (NO) in human chondrocytes. Celecoxib (10 ?M) inhibits COX-1 mediated PGD2, and nitric oxide synthase (NOS) mediated NO in human OA-affected cartilage. Furthermore, celecoxib (1 ?M) counter balances (IL-1? induced+PGD2 modulated) levels of NO and PGE2 in human OA-affected cartilage and chondrocytes to basal levels. These results show concentration-dependent, pro- and anti-inflammatory activity of PGD2 in human chondrocytes and cartilage, which can be neutralized by celecoxib. In view of the broad prostaglandin dependent and independent mechanism of action of celecoxib, these observations further reaffirm the broader role of celecoxib as a "Disease Modifying Drug" for human Osteoarthritis. PMID:23603366

Dave, Mandar; Amin, Ashok R

2013-04-01

75

Automated Test Assembly for Cognitive Diagnosis Models Using a Genetic Algorithm  

ERIC Educational Resources Information Center

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…

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

2009-01-01

76

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

77

Power transformer fault diagnosis based on support vector machine with cross validation and genetic algorithm  

Microsoft Academic Search

Support vector machine (SVM) classifier has been successfully applied to power transformer fault diagnosis. However, there is no theoretical basis or effective method to select appropriate SVM classifier parameters which have a crucial influence on the classification accuracy. Currently, the main method is cut and try based on experience. In this study, genetic algorithm (GA) is employed to optimize the

JinLiang Yin; YongLi Zhu; GuoQin Yu

2011-01-01

78

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

Microsoft Academic Search

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

Qiang Wang; Huanhuan Chen; Yi Shen

2008-01-01

79

Fault diagnosis method for machinery in unsteady operating condition by instantaneous power spectrum and genetic programming  

Microsoft Academic Search

This paper proposes a fault diagnosis method for plant machinery in an unsteady operating condition using instantaneous power spectrum (IPS) and genetic programming (GP). IPS is used to extract feature frequencies of each machine state from measured vibration signals for distinguishing faults by relative crossing information. Excellent symptom parameters for detecting faults are automatically generated by the GP. The excellent

Peng Chen; Masatoshi Taniguchi; Toshio Toyota; Zhengja He

2005-01-01

80

Failure diagnosis method for machinery in unsteady operating condition by instantaneous power spectrum and genetic programming  

Microsoft Academic Search

The paper proposes a failure diagnosis method for machinery in unsteady operating condition using instantaneous power spectrum (IPS) and genetic programming (GP). The IPS is used to extract feature frequency of each machine state from measured vibration signal for distinguishing failures by the Relative Crossing Information (RCI). Excellent symptom parameters for detecting failures are automatically generated by GP. The method

Peng Chen; Toshio Toyota; Masatoshi Taniguchi; Fang Feng; T. Hiho

2000-01-01

81

Ethical Challenges in Assisted Reproduction: The Place of Preimplantation Genetic Diagnosis in a Just Society.  

PubMed

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

Whetstine, Leslie M

2013-12-11

82

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

NSDL National Science Digital Library

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

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

2010-04-20

83

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

PubMed

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

Greenberg, Steven A; Walsh, Ronan J

2005-04-01

84

Small Ruminant Lentiviruses: Genetic Variability, Tropism and Diagnosis  

PubMed Central

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

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

2013-01-01

85

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

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

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

86

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

PubMed Central

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

2014-01-01

87

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

PubMed Central

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

Costain, Gregory; Bassett, Anne S

2012-01-01

88

Blastocystis: Genetic diversity and molecular methods for diagnosis and epidemiology  

PubMed Central

Blastocystis, an unusual anaerobic, single-celled stramenopile, is a remarkably successful intestinal parasite of a vast array of host species including humans. Fecal Deoxyribonucleic acid (DNA) analysis by nucleic-acid based methods in particular has led to significant advances in Blastocystis diagnostics and research over the past few years enabling accurate identification of carriers and molecular characterization by high discriminatory power. Moreover, Blastocystis comprises a multitude of subtypes (STs) (arguably species) many of which have been identified only recently and molecular epidemiological studies have revealed a significant difference in the distribution of STs across host species and geographical regions. Having a cosmopolitan distribution, the parasite is a common laboratory finding in the stools of individuals with and without intestinal symptoms across the entire globe and while the parasite remains extremely difficult to eradicate and isolate in culture, appropriate molecular tools are now available to resolve important questions such as whether the clinical outcome of colonization is linked to ST and whether Blastocystis is transmitted zoonotically. This review summarizes some of the recent advances in the molecular diagnosis of Blastocystis and gives an introduction to Blastocystis STs, including a recommendation of subtyping methodology based on recent data and method comparisons. A few suggestions for future directions and research areas are given in the light of relevant technological advances and the availability of mitochondrial and nuclear genomes. PMID:23961438

Stensvold, Christen Rune

2013-01-01

89

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

PubMed Central

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

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

90

Predictive diagnosis in familial adenomatous polyposis: evaluation of molecular genetic and ophthalmologic methods.  

PubMed

Familial adenomatous polyposis (FAP) is an autosomal-dominant precancerous condition characterized by the appearance of hundreds to thousands of colorectal polyps. The responsible gene (APC) has been mapped and identified. The cancer prevention policy for persons at risk (children and sibs of FAP patients) implies an early diagnosis of the disease. A presymptomatic diagnosis allows to limit the regular rectosigmoidoscopic examination to those persons having inherited the disease gene. Presymptomatic diagnosis can be achieved by molecular genetic methods (direct and indirect genotype analysis) and by funduscopic examination of retinal pigment anomalies that are characteristic for FAP. The aim of this study was to examine the power of the molecular genetic and ophthalmologic methods for presymptomatic diagnosis in FAP. For this purpose 60 FAP families with 171 persons at risk were examined. By direct mutation analysis a presymptomatic diagnosis was achieved in 32% of the persons at risk; indirect genotype analysis was possible in 88% of the families in which more than one FAP patient was available. The ophthalmologic examination allowed a presymptomatic conclusion in 79% of the persons at risk. In no case there was a discrepancy in the results between the methods applied. The ophthalmologic presymptomatic test is useful especially in families where the index patients has a new mutation in the APC gene that has not been identified. PMID:8291275

Caspari, R; Friedl, W; Böker, T; Augustin, A; Mandl, M; Jaeger, K; Gallkowski, K; Propping, P

1993-11-01

91

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

SciTech Connect

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

Randall, T.

1990-12-26

92

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

PubMed Central

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

Verma, Ashok

2014-01-01

93

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

PubMed

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

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

2013-01-01

94

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

PubMed Central

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

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

2013-01-01

95

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

PubMed

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

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

2014-11-01

96

Role of genetics in the diagnosis and prognosis of Crohn's disease  

PubMed Central

Considering epidemiological, genetic and immunological data, we can conclude that the inflammatory bowel diseases are heterogeneous disorders of multifactorial etiology in which hereditability and environment interact to produce the disease. It is probable that patients have a genetic predisposition for the development of the disease coupled with disturbances in immunoregulation. Several genes have been so far related to the diagnosis of Crohn’s disease. Those genes are related to innate pattern recognition receptors, to epithelial barrier homeostasis and maintenance of epithelial barrier integrity, to autophagy and to lymphocyte differentiation. So far, the most strong and replicated associations with Crohn’s disease have been done with NOD2, IL23R and ATG16L1 genes. Many genes have so far been implicated in prognosis of Crohn’s disease and many attempts have been made to classify genetic profiles in Crohn’s disease. CARD15 seems not only a susceptibility gene, but also a disease-modifier gene for Crohn’s disease. Enriching our understanding on Crohn’s disease genetics is important but when combining genetic data with functional data the outcome could be of major importance to clinicians. PMID:22253516

Tsianos, Epameinondas V; Katsanos, Konstantinos H; Tsianos, Vasileios E

2012-01-01

97

Role of genetics in the diagnosis and prognosis of Crohn's disease  

PubMed Central

Considering the epidemiological, genetic and immunological data, we can conclude that the inflammatory bowel diseases are heterogeneous disorders of multifactorial etiology in which hereditability and environment interact to produce the disease. It is probable that patients have a genetic predisposition for the development of the disease coupled with disturbances in immunoregulation. Several genes have so far been related to the diagnosis of Crohn’s disease. These genes are related to innate pattern recognition receptors, to epithelial barrier homeostasis and maintenance of epithelial barrier integrity, to autophagy and to lymphocyte differentiation. So far, the strongest and most replicated associations with Crohn’s disease have been demonstrated with NOD2, IL23R and ATG16L1 genes. Many genes have so far been implicated in the prognosis of Crohn’s disease and many attempts have been made for classification of genetic profiles in Crohn’s disease. CARD15 seems to be not only a susceptibility gene, but also a disease-modifier gene for Crohn’s disease. Enriching our understanding of Crohn’s disease genetics is of value, but when combining genetic data with functional data the outcome could be of major importance to clinicians. PMID:22219593

Tsianos, Epameinondas V; Katsanos, Konstantinos H; Tsianos, Vasileios E

2011-01-01

98

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

PubMed

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

Lu, Chunhong; Zhu, Zhaomin; Gu, Xiaofeng

2014-09-01

99

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

PubMed Central

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

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

2013-01-01

100

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

PubMed

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

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

2013-01-01

101

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

PubMed Central

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

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

102

Fish based preimplantation genetic diagnosis to prevent DiGeorge syndrome  

Microsoft Academic Search

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

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

2009-01-01

103

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

PubMed Central

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

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

2014-01-01

104

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

Microsoft Academic Search

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

Xu Lishuang; Cai Tao; Deng Fang; Liu Xin

2011-01-01

105

Intelligent medical disease diagnosis using improved hybrid genetic algorithm--multilayer perceptron network.  

PubMed

An improved genetic algorithm procedure is introduced in this work based on the theory of the most highly fit parents (both male and female) are most likely to produce healthiest offspring. It avoids the destruction of near optimal information and promotes further search around the potential region by encouraging the exchange of highly important information among the fittest solution. A novel crossover technique called Segmented Multi-chromosome Crossover is also introduced. It maintains the information contained in gene segments and allows offspring to inherit information from multiple parent chromosomes. The improved GA is applied for the automatic and simultaneous parameter optimization and feature selection of multi-layer perceptron network in medical disease diagnosis. Compared to the previous works, the average accuracy of the proposed algorithm is the best among all algorithms for diabetes and heart dataset, and the second best for cancer dataset. PMID:23479268

Ahmad, Fadzil; Isa, Nor Ashidi Mat; Hussain, Zakaria; Osman, Muhammad Khusairi

2013-04-01

106

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

E-print Network

? The authors have no financial conflicts of interest. Congenital lipoid adrenal hyperplasia (CLAH) is caused by mutations to the steroidogenic acute regulatory protein (StAR) gene associated with the inability to synthesize all adrenal and gonadal steroids. Inadequate treatment in an infant with this condition may result in sudden death from an adrenal crisis. We report a case in which CLAH developed in Korean siblings; the second child was prenatally diagnosed because the first child was affected and low maternal serum estriol was detected in a prenatal screening test. To our knowledge, this is the first prenatal diagnosis of the Q258X StAR mutation, which is the only consistent genetic cluster identified to date in Japanese and Korean populations. Key Words: ?Lipoid hyperplasia, congenital, prenatal, sibling

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

2011-01-01

107

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

PubMed Central

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

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

2011-01-01

108

Prenatal diagnosis of congenital lipoid adrenal hyperplasia (CLAH) by molecular genetic testing in Korean siblings.  

PubMed

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

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

2011-11-01

109

Parental decisions following prenatal diagnosis of chromosomal abnormalities: implications for genetic counseling practice in Japan.  

PubMed

Parental decision-making to terminate or continue a pregnancy was studied after prenatal diagnosis of a chromosome aneuploidy among a sample of patients around the city of Nagoya, Japan. A total of 1,051 amniocentesis cases at 15-18 weeks of gestation were analyzed. Of these, 60 cases of chromosomal anomalies with aneuploidies were diagnosed by conventional cytogenetic analysis. Of the 45 diagnoses of autosomal chromosome aneuploidies, pregnancy was terminated in 93.3 % of the cases. Of the 15 cases diagnosed with sex chromosome aneuploidy, pregnancy was terminated in 46.7 %. Differences in parental decisions with respect to maternal age, gestational week at diagnosis, number of pregnancies per individual and existing number of children were not significant in patients diagnosed either with autosomal or sex chromosome aneuploidy. The findings indicate that when diagnosed with a chromosome aneuploidy in which a severe prognosis was expected, most couples decided to terminate the pregnancy in Japan. Implications of these findings for expanding the profession of genetic counseling are discussed and research recommendations are provided. PMID:25082303

Suzumori, Nobuhiro; Kumagai, Kyoko; Goto, Shinobu; Nakamura, Akira; Sugiura-Ogasawara, Mayumi

2015-02-01

110

Genetic diagnosis in Lafora disease: genotype-phenotype correlations and diagnostic pitfalls.  

PubMed

Lafora disease (LD) can be diagnosed by skin biopsy, but this approach has both false negatives and false positives. Biopsies of other organs can also be diagnostic but are more invasive. Genetic diagnosis is also possible but can be inconclusive, for example, in patients with only one heterozygous EPM2A mutation and patients with apparently homozygous EPM2B mutations where one parent is not a carrier of the mutation. We sought to identify occult mutations and clarify the genotypes and confirm the diagnosis of LD in patients with apparent nonrecessive disease inheritance. We used single nucleotide polymorphism, quantitative PCR, and fluorescent in situ hybridization analyses. We identified large EPM2A and EPM2B deletions undetectable by PCR in the heterozygous state and describe simple methods for their routine detection. We report a coding sequence change in several patients and describe why the pathogenic role of this change remains unclear. We confirm that adult-onset LD is due to EPM2B mutations. Finally, we report major intrafamilial heterogeneity in age at onset in LD. PMID:17389303

Lohi, H; Turnbull, J; Zhao, X C; Pullenayegum, S; Ianzano, L; Yahyaoui, M; Mikati, M A; Quinn, N P; Franceschetti, S; Zara, F; Minassian, B A

2007-03-27

111

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

PubMed Central

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

Roma-Rodrigues, Catarina; Fernandes, Alexandra R

2014-01-01

112

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

PubMed

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

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

2013-09-01

113

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

PubMed Central

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

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

2012-01-01

114

CC16 inhibits the migration of eosinophils towards the formyl peptide fMLF but not towards PGD2.  

PubMed

Clara cell 16-kDa (CC16) is an anti-inflammatory protein chiefly produced in the lung epithelium. CC16 has been shown to inhibit the migration of rabbit neutrophils and human monocytes toward the formyl peptide N-formyl-methionine-leucin-phenylalanin (fMLF). Eosinophils migrate towards prostaglandin D2 (PGD(2)) and CC16 has been shown to bind to PGD(2). Therefore we investigated if CC16 could inhibit the migration of human eosinophils and neutrophils towards fMLF and/or PGD(2). Migration of eosinophils and neutrophils was assessed in a microplate migration system using specific ligands and receptor antagonists. CC16 inhibited the migration of eosinophils and neutrophils toward fMLF, which is likely to result from the interaction of CC16 with members of the formyl-peptide receptor family. However, CC16 did not inhibit eosinophil migration towards PGD(2). We therefore propose that CC16 may down-modulate the entry of human eosinophils and neutrophils into the airways during inflammation in the lung. PMID:19132521

Johansson, Sofi; Andersson, Kerstin; Wennergren, Göran; Wennerås, Christine; Rudin, Anna

2009-04-01

115

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

NASA Astrophysics Data System (ADS)

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

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

1999-05-01

116

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

PubMed Central

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

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

117

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

PubMed

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

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

118

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

PubMed Central

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

2012-01-01

119

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

PubMed Central

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

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

2014-01-01

120

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

SciTech Connect

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

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

1994-09-01

121

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

SciTech Connect

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

VandeBerg, J.L.; Aivaliotis, M.J.; Samollow, P.B. (Southwest Foundation for Biomedical Research, San Antonio, TX (United States))

1992-12-01

122

Genetic relationships between Dioscorea alata L. cultivars  

Microsoft Academic Search

Isozyme variation was studied to determine genetic relationships among 269 cultivars of Dioscorea alata originating from the South Pacific, Asia, Africa and the Caribbean. Four polymorphic enzyme systems (MDH, PGI, SkDH, 6PGD) revealed 66 isozyme phenotypes, or zymotypes, each uniquely characterized by the presence or absence of 27 electromorphs. Identical zymotypes were found to be distributed in different geographical areas

V. Lebot; B. Trilles; J. L. Noyer; J. Modesto

1998-01-01

123

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

PubMed

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

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

2014-12-01

124

Genetic Approaches for the Diagnosis and Treatment of Congenital Tooth Agenesis  

E-print Network

disorder, such new therapeutic strategies for the prevention of tooth agenesis should be attempted. In this research project I have pursued two objectives: 1.) Basic research into the molecular genetics and therapeutics of the tooth agenesis gene PAX9...

Bonds, John Carless

2014-08-06

125

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

Microsoft Academic Search

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

Meral Özgüç

2011-01-01

126

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

PubMed

Variants in 11 genes of the RAS/MAPK signaling pathway have been causally linked to the neuro-cardio-facio-cutaneous syndromes group (NCFCS). Recently, A2ML1 and RIT1 were also associated with these syndromes. Because of the genetic and clinical heterogeneity of NCFCS, it is challenging to define strategies for their molecular diagnosis. The aim of this study was to develop and validate a massive parallel sequencing (MPS)-based strategy for the molecular diagnosis of NCFCS. A multiplex PCR-based strategy for the enrichment of the 13 genes and a variant prioritization pipeline was established. Two sets of genomic DNA samples were studied using the Ion PGM System: (1) training set (n=15) to optimize the strategy and (2) validation set (n=20) to validate and evaluate the power of the new methodology. Sanger sequencing was performed to confirm all variants and low covered regions. All variants identified by Sanger sequencing were detected with our MPS approach. The methodology resulted in an experimental approach with a specificity of 99.0% and a maximum analytical sensitivity of ?98.2% with a confidence of 99%. Importantly, two patients (out of 20) harbored described disease-causing variants in genes that are not routinely tested (RIT1 and SHOC2). The addition of less frequently altered genes increased in ?10% the diagnostic yield of the strategy currently used. The presented workflow provides a comprehensive genetic screening strategy for patients with NCFCS in a fast and cost-efficient manner. This approach demonstrates the potential of a combined MPS-Sanger sequencing-based strategy as an effective diagnostic tool for heterogeneous diseases.European Journal of Human Genetics advance online publication, 4 June 2014; doi:10.1038/ejhg.2014.97. PMID:24896146

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

2014-06-01

127

Support vector machine with genetic algorithm for machinery fault diagnosis of high voltage circuit breaker  

Microsoft Academic Search

Based on empirical mode decomposition (EMD) method and support vector machine (SVM), a new method for the fault diagnosis of high voltage circuit breaker (CB) is proposed. The feature extraction method based on improved EMD energy entropy is detailedly analyzed and SVM is employed as a classifier. Radial basis function (RBF) is adopted as the kernel function of SVM and

Jian Huang; Xiaoguang Hu; Fan Yang

2011-01-01

128

New polymorphic sites within ornithine transcarbamylase gene: population genetics studies and implications for diagnosis  

Microsoft Academic Search

Ornithine transcarbamylase (OTC) deficiency, transmitted as an X-linked trait, is the most common disorder of the urea cycle. At least 3.5% out of more than 230 mutations consist of large gene deletions, involving one or more exons. Only in 78% of OTC patients the diagnosis was confirmed on DNA level. We analysed OTC intragenic polymorphisms and haplotypes, in an attempt

Lu??sa Azevedo; Larisa Stolnaja; Evzenie Tietzeova; Martin Hrebicek; Eva Hruba; Laura Vilarinho; António Amorim; Lenka Dvorakova

2003-01-01

129

Genetic testing and first presymptomatic diagnosis in Moroccan families at high risk for breast/ovarian cancer  

PubMed Central

Germline mutations in the BRCA1 and BRCA2 genes highly predispose to breast and ovarian cancers and are responsible for a substantial proportion of familial breast and ovarian cancers. No female individuals from families from Morocco affected by breast cancer with mutations of these genes have previously been reported, and clinicians in Morocco are unaccustomed to dealing with healthy female individuals carrying mutations in the BRCA genes. This study aimed to report the initial experience of a group of Moroccan investigators carrying out predictive genetic testing to detect a known familial mutation in healthy Moroccan females with a high risk of developing breast cancer and to introduce supervision of these asymptomatic female carriers as a new approach in the prevention and early diagnosis of breast and ovarian cancers in Morocco. Presymptomatic diagnosis was carried out using DNA genetic testing in 5 healthy Moroccan female individuals from three families with an elevated risk of developing breast cancer. These are the first Moroccan families reported to be affected by breast cancers associated with BRCA mutations. Presymptomatic diagnosis was carried out for breast cancer in 5 female individuals from three Moroccan families with BRCA mutations. Two of the families are the first reported incidence of the founder mutation Ashkenazi BRCA1-185_186delAG in Moroccan patients. The third family carried the known BRCA2 mutation c.5073dupA/p.trp1692metfsX3. We tested the presence of these mutations in 5 asymptomatic healthy females from the three families. Two sisters from family 1 carried the BRCA1-185_186delAG mutation, whereas the third female individual from family 2 carried the c.5073dupA/p.trp1692metfsX3 mutation. However, one healthy female individual and her mother from family 3 did not carry the familial mutation of the BRCA1 gene. This study found BRCA mutations in three asymptomatic subjects, suggesting that this is the first step towards the development of persistent medical monitoring of females from families with a history of breast and ovarian cancers. Consequently, it is crucial for oncologists in Morocco to initiate the supervision of healthy female individuals with genetic defects which may lead to hereditary cancers. PMID:22866093

LAARABI, FATIMA ZAHRA; JAOUAD, IMANE CHERKAOUI; OULDIM, KARIM; ABOUSSAIR, NISRINE; JALIL, ABDELOUAHED; GUEDDARI, BRAHIM EL KHALIL EL; BENJAAFAR, NOUREDDINE; SEFIANI, ABDELAZIZ

2011-01-01

130

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

PubMed Central

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

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

2014-01-01

131

[Beyond the diagnosis of a genetic disease, the question of informing the relatives].  

PubMed

The examination of a person's genetic characteristics is not a classic diagnostic. It concerns the gene pool of an entire family. It is valid in the present and may affect some part of the future. The diseases that it reveals, sometime very serious ones, may or may not be treated. But genetic advice allows sometimes to preventing some of these diseases. The 2004 Bioethics Law makes the provision that in case a serious genetic anomaly is diagnosed during the examination of a person's genetic characteristics, the medical doctor informs the person or its legal representative of the risks that his silence could cause to the potentially concerned family members as long as prevention measures or care can be offered to them. For these reasons, besides the specificity of the diagnostic for the person directly concerned, there is also the question of the right of other people, like family members, to be informed of the diagnostic. As such, there is an ethical conflict between medical confidentiality owed to each patient and the duty of information. The pharmacist must know the medical confidentiality rules that frame this information. He must also know the different patient attitudes and must be able to encourage him to inform his family because the future if not the life of others may depend on this information. PMID:19152847

Pellerin, P

2009-01-01

132

Sixteen years' experience of counselling, diagnosis, and prenatal detection in one genetic centre: progress, results, and problems.  

PubMed Central

The work of one Genetic Centre over 16 years, covering about 14 000 kinships, is described. The numbers registered in a year increased from an average of 477 in the early 1960s to 1612 in 1976/1977. The increase is largely, but not entirely, attributable to the advent of prenatal diagnosis, and an account is given of our experience with this. In 1916 patients who had a successful amniocentesis, results indicative of fetal abnormality were found in 4.3% and a balanced translocation was found in an additional 0.9%. Results indicative of fetal abnormality were found in 3.5% of mothers referred because of a maternal age of 40 or more, 3.9% referred because of a high risk of neural tube defect, and 19.3% referred because of a high risk of an inborn error of metabolism. A number of cases with difficult diagnostic problems are described. PMID:469894

Polani, P E; Alberman, E; Alexander, B J; Benson, P F; Berry, A C; Blunt, S; Daker, M G; Fensom, A H; Garrett, D M; McGuire, V M; Roberts, J A; Seller, M J; Singer, J D

1979-01-01

133

Iron overload (with attention to genetic testing and diagnosis\\/management of HFE wild type patients)  

Microsoft Academic Search

Opinion statement  The discovery of the HFE, HJV, HAMP, TfR2, and SLC40A1 genes and preliminary understanding of their roles in iron homeostasis have contributed tremendously to our understanding\\u000a of the pathogenesis of genetic hemochromatosis. Although several new models of iron metabolism have been proposed, some key\\u000a “sensor” steps of iron absorption in the enterocytes and of iron storage in hepatocytes and

Narendra Siddaiah; Kris V. Kowdley

2006-01-01

134

Pituitary Tumors in Childhood: an update in their diagnosis, treatment and molecular genetics  

PubMed Central

Pituitary tumors are rare in childhood and adolescence, with a reported prevalence of up to 1 per million children. Only 2 - 6% of surgically treated pituitary tumors occur in children. Although pituitary tumors in children are almost never malignant and hormonal secretion is rare, these tumors may result in significant morbidity. Tumors within the pituitary fossa are of two types mainly, craniopharyngiomas and adenomas; craniopharyngiomas cause symptoms by compressing normal pituitary, causing hormonal deficiencies and producing mass effects on surrounding tissues and the brain; adenomas produce a variety of hormonal conditions such as hyperprolactinemia, Cushing disease and acromegaly or gigantism. Little is known about the genetic causes of sporadic lesions, which comprise the majority of pituitary tumors, but in children, more frequently than in adults, pituitary tumors may be a manifestation of genetic conditions such as multiple endocrine neoplasia type 1 (MEN 1), Carney complex, familial isolated pituitary adenoma (FIPA), and McCune-Albright syndrome. The study of pituitary tumorigenesis in the context of these genetic syndromes has advanced our knowledge of the molecular basis of pituitary tumors and may lead to new therapeutic developments. PMID:18416659

Keil, Margaret F.; Stratakis, Constantine A.

2009-01-01

135

Intérêt du génotypage du sexe fœtal dans le sang maternel dans les indications de diagnostic génétique préimplantatoire de sexe  

Microsoft Academic Search

Objective. – Couples with a risk of transmitting X-linked diseases included in a preimplantation genetic diagnosis (PGD) center need early and rapid fetal sex determination during pregnancy in two situations. The first situation corresponds to control of embryo sexing after PGD, the second one being that of couples in PGD program having a spontaneous pregnancy. Determination of fetal sex can

G Tachdjian; J. M Costa; N Frydman; P Ray; A Le Dû; V Kerbrat; P Ernault; R Frydman

2003-01-01

136

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

Microsoft Academic Search

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

M. Jusuf; J. Pernes

1985-01-01

137

Preliminary study of genetic diversity in Swedish flax (Linum usitatissimum)  

Microsoft Academic Search

To investigate the genetic diversity of Linum usitatissimumL. in Sweden, 18 accessions, including 13 cultivars and five landraces, were analysed. This study was based on genetic variation in three enzyme systems (i.e., PGD, GPI and MDH) by using horizontal starch gel electrophoresis. The total genetic diversity of the studied flax material was very high (HT= 0.62). Even though the highest

E. Månsby; O. Díaz; R. von Bothmer

2000-01-01

138

Midbrain-Hindbrain Malformations: Advances in Clinical Diagnosis, Imaging, and Genetics  

PubMed Central

Historically, the midbrain and hindbrain (MBHB) have been considered “support staff” for the cerebrum, which has typically been acknowledged as the most important part of the brain. Radiologists and pathologists did not regularly examine these structures, also known as the brainstem and cerebellum, because they are small and difficult to remove without damage. With recent improvements in neuroimaging, neuropathology and neurogenetics, many developmental disorders of the MBHB have emerged as significant causes of neurodevelopmental dysfunction. This review provides an overview of MBHB disorders important to clinicians and developmental biologists. A basic understanding of MBHB embryology is essential to understanding the malformations that occur in MBHB structures; therefore, a brief embryology review is provided, as is a review of MBHB anatomy as assessed by MRI, and an approach to MRI analysis of the individual structures. Clinical features common to many MBHB disorders are presented, followed by a more in depth summary of the clinical presentations, MRI features and genetic causes of many common, and some less common, malformations. Research advances that may change how we treat these patients in the future are briefly discussed. The information provided in this review will improve the clinical acumen of the practicing neurologist in regard to malformations of the MBHB, while at the same time adding to their understanding of brainstem and cerebellar development, genetics, and function. PMID:23518331

Doherty, Dan; Millen, Kathleen J.; Barkovich, A. James

2014-01-01

139

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

PubMed

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

Zimmer, Vincent; Lammert, Frank

2014-06-01

140

Design and validation of a colorimetric test for the genetic diagnosis of hemochromatosis using ?-phosphorothioate nucleotides.  

PubMed

Hereditary hemochromatosis is an autosomal recessive disease highly prevalent in Northern Europe. Here we describe the performance of a genetic test for two mutations of the HFE gene (C282Y and H63D). It is based on a solid-phase PCR coupled with an ?-phosphorothioate-mediated primer extension, conferring resistance to hydrolysis by ExoIII. Next, Elisa-like detection allows a colorimetric reading of the genetic test. We performed 322 tests (212 on the C282Y mutation, 110 on the H63D mutation) and compared the results with the RFLP method. Using OD ranges giving the minimum of uncertainty, the tests lead to high specificity and sensitivity, and they address the detection of mutated or normal bases in the HFE gene or the deduced phenotype (safe or ill), with positive predictive values or negative ones greater than 0.96. This method is therefore proposed as a primary test or as a confirming test. PMID:23674081

Brugère, Jean-François; Gobron, Stéphane; Baud, Eric; Cailloux, Fabrice

2013-08-01

141

[Genetic diagnosis of thalassemia mutations with free fetal DNA in pregnant plasma].  

PubMed

This research was aimed to develop a simple, rapid, accurate and non-invasive method by means of flow-through hybridization technology, which can be used for molecular screening and early prenatal diagnosis for detecting common ?-thalassemias mutational genotypes. By using PCR technology combined with flow-through hybridization of low-density gene chip technology, the 6 sets of PCR primer single tube multiplex PCR system and 29 types of DNA probes were designed, then the mutational thalassemias in foetus DNA was rapidly detected in total of 60 anaemia pregnant women plasma. The results showed that 4 cases with deletional ?-thalassemias, 3 cases with ?-thalassemias, 1 case with mixed type of ? & ?-thalassemias were detected in foetus DNA of 60 pregnant women plasmas. It is concluded that the method presented in this study is easy to handle, rapid, reliable and cost-effective for detecting 3 common deletional ?-thalassemias and 17 common mutational ?-thalassemia. PMID:24156437

Lin, Xiao-Rong; You, Liu-Xia; Chen, Yong

2013-10-01

142

Prenatal diagnosis of female monozygotic twins discordant for Turner syndrome: implications for prenatal genetic counselling.  

PubMed

We describe a set of monozygotic (MZ) female twins, one of whom presented with a typical Turner syndrome (TS) phenotype and the other a normal female phenotype. Prenatal fetal ultrasonographic examination showed a monochorial diamniotic pregnancy with a hygroma colli and growth delay in Twin A and no anomalies in Twin B. Karyotypic analysis performed on fetal blood samples demonstrated a 46,XX/45,X (23/2) mosaicism in Twin A and a normal 46,XX chromosome constitution in Twin B. At birth, Twin A presented with a typical TS and Twin B had a normal female phenotype. Postnatal cytogenetic investigation of blood lymphocytes showed the same 46,XX/45,X mosaicism in both twins: 46,XX/45,X (40/7) in Twin A and 46,XX/45,X (40/5) in Twin B. Further investigations at the age of 10 months showed in Twin A a 46,XX/45,X (98/2) mosaicism in lymphocytes and 100% of 45,X (50 analysed cells) in fibroblasts, and in Twin B a normal 46,XX (100 analysed cells) chromosome constitution in lymphocytes but a mild 46,XX/45,X (78/2) mosaicism in fibroblasts. Monozygosity was confirmed by molecular analysis. To our knowledge, this is the first report of prenatal diagnosis of MZ female twins discordant for TS. Review of reported sets of MZ female twins (eight cases) or triplets (one case) discordant for TS shows, as in the present case, that the phenotype correlates better with the chromosomal distribution of mosaicism in fibroblasts than in lymphocytes. In the blood of MZ twins chimerism may modify the initial allocation of the mosaicism. These results suggest that, in cases of prenatal diagnosis of MZ female twins discordant for TS, the phenotype of each twin would be better predicted from karyotype analysis of cells from amniotic fluid than from fetal blood. PMID:12210579

Gilbert, B; Yardin, C; Briault, S; Belin, V; Lienhardt, A; Aubard, Y; Battin, J; Servaud, M; Philippe, H J; Lacombe, D

2002-08-01

143

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

PubMed Central

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

2013-01-01

144

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

PubMed Central

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

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

2014-01-01

145

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

PubMed

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

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

2014-06-15

146

[New primary malignancies after breast cancer diagnosis: interplay of genetics, risk factors and treatment modalities].  

PubMed

Significant advances in early breast cancer detection and increased quality of care within developed countries resulted in longer than five years survival in almost 90% of women diagnosed and treated for breast cancer. One in twenty women diagnosed with breast cancer will develop a new primary non-breast malignancy within 10 years from initial diagnosis. Mutations in BRCA 1 i 2, RAD51C, MMR, p53, CDKN2A and 113insArg genes are linked with increased risk of breast cancer and other cancer sites. It seems that treatment modalities also play significant role in development of new primary malignancies. Tissues that receive higher doses of radiation during radiotherapy of breast cancer are under increased risk of developing new primary tumor, especially in younger women, ten years after the treatment. Chemotherapy may cause higher incidence of leukemia and myelodysplastic syndrome but lower overall risk for development of other malignancies. Connection between tamoxifen therapy and increased risk of endometrial cancer is well known and confirmed also in recent studies. The true mechanism of cancer development is still unclear. Significance of hereditary factors, possible common environmental risk factors or unwanted side effects of the specific anticancer treatments are yet to be discovered. PMID:23607174

Plaveti?, Natalija Dedi?; Bari?, Marina; Solari?, Mladen; Vrbanec, Damir

2013-01-01

147

Histologic and Genetic Advances in Refining the Diagnosis of “Undifferentiated Pleomorphic Sarcoma”  

PubMed Central

Undifferentiated pleomorphic sarcoma (UPS) is an inclusive term used for sarcomas that defy formal sub-classification. The frequency with which this diagnosis is assigned has decreased in the last twenty years. This is because when implemented, careful histologic assessment, immunohistochemistry, and ultra-structural evaluation can often determine lineage of differentiation. Further attrition in the diagnostic frequency of UPS may arise by using array-comparative genomic hybridization. Gene expression arrays are also of potential use as they permit hierarchical gene clustering. Appraisal of the literature is difficult due to a historical perspective in which specific molecular diagnostic methods were previously unavailable. The American Joint Committee on Cancer (AJCC) classification has changed with different inclusion criteria. Taxonomy challenges also exist with the older term “malignant fibrous histiocytoma” being replaced by “UPS”. In 2010 an analysis of multiple sarcoma expression databases using a 170-gene predictor, re-classified most MFH and “not-otherwise-specified” (NOS) tumors as liposarcomas, leiomyosarcomas or fibrosarcomas. Interestingly, some of the classifier genes are potential molecular therapeutic targets including Insulin-like growth factor 1 (IGF-1), Peroxisome proliferator-activated receptor ? (PPAR?), Nerve growth factor ? (NGF ?) and Fibroblast growth factor receptor (FGFR). PMID:24216705

Kelleher, Fergal C.; Viterbo, Antonella

2013-01-01

148

Genetic diagnosis by comparative genomic hybridization in adult de novo acute myelocytic leukemia.  

PubMed

A total of 127 adult de novo acute myelocytic leukemia (AML) patients were analyzed by comparative genomic hybridization (CGH) at diagnosis. Conventional cytogenetic analysis (CCA) showed a normal karyotype in 45 cases and an abnormal karyotype in 56 cases; in the remaining cases, CCA either failed to yield sufficient metaphase cells (19/26) or was not done (7/26). Abnormal CGH profiles were identified in 39 patients (30.7%). DNA copy number losses (61%) were high compared to gains (39%), whereas partial chromosome changes (76%) were more common than whole chromosomes changes (24%). Recurrent losses were detected on chromosomes 7, 5q (comprising bands 5q15 to 5q33), 7q (7q32 approximately q36), 16q (16q13 approximately q21), and 17p, and gains were detected on chromosomes 8, 22, and 3q (comprising bands 3q26.1 approximately q27). Furthermore, distinct amplifications were identified in chromosome regions 21q, 13q12 approximately q13, and 13q21.1. No cryptic recurrent chromosomal imbalances were identified by CGH in cases with normal karyotypes. The concordance between CGH results and CCA was 72.5%. In the remaining cases, CGH gave additional information compared to CCA (20%) and partially failed to identify the alterations previously detected by CCA (7.5%). The majority of discrepancies arose from the limitations of the CGH technique, such as insensitivity to detect unbalanced chromosomal changes when occurring in a low proportion of cells. CGH increased the detection of unbalanced chromosomal alterations and allowed precise defining of partial or uncharacterized cytogenetical abnormalities. Application of the CGH technique is thus a useful complementary diagnostic tool for CCA in de novo AML cases with abnormal karyotypes or with unsuccessful cytogenetics. PMID:15325089

Casas, Sílvia; Aventín, Anna; Fuentes, Francisca; Vallespí, Teresa; Granada, Isabel; Carrió, Anna; Angel Martínez-Climent, José; Solé, Francesc; Teixidó, Montserrat; Bernués, Marta; Duarte, José; Maria Hernández, Jesús; Brunet, Salut; Dolors Coll, Maria; Sierra, Jorge

2004-08-01

149

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

PubMed

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

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

2015-02-01

150

Medical genetics  

SciTech Connect

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.

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

1995-10-01

151

Sheep gene mapping by somatic cell hybridization: four syntenic groups: ENO1-PGD, ME1PGM3, LDHB-PEPB-TPI, and G6PD-PGK-GALA  

Microsoft Academic Search

Gene segregation for 16 ovine enzyme markers was studied in 25 independently derived hamster-sheep hybrids. The results show four syntenic groups, ENOl-PGD, ME1-PGM3, LDHB-PEPB-TPI, G6PD-PGK-GALA, and markers for six different chromosomes: PGM1 (or PGM2?), IDH1, GPI, LDHA, MDH2, and ADA.Copyright © 1981 S. Karger AG, Basel

N. Saïdi-Mehtar; M.-C. Hors-Cayla; Nguyen van Cong

1981-01-01

152

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

PubMed

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

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

2012-09-01

153

Central nervous system effects of arachidonic acid, PGE2, PGF2 alpha, PGD2 and PGI2 on gastric secretion in the rat.  

PubMed Central

The effects of arachidonic acid, prostaglandin E2 (PGE2), PGF2 alpha, PGD2 and PGI2 on gastric secretion (acid, pepsin and volume) after intracerebroventricular administration were investigated in conscious, pylorus-ligated rats. Arachidonic acid 30-1000 micrograms had no effect on gastric secretion. PGE2 3 and 10 micrograms, reduced gastric secretion as measured 1 hour after injection, although the inhibition induced by 3 micrograms disappeared by 2 h. PGF2 alpha 10 and 30 micrograms, inhibited gastric secretion as measured after 1 h, whereas no change was observed in the gastric contents collected 2 h after 10 micrograms of PGF2 alpha. Intramuscular injection of 30 micrograms of PGF2 alpha had no effect on gastric secretion. Intracerebroventricular administration of 1-30 micrograms of PGD2 or PGI2 had no effect on gastric secretion. The results indicate that PGE2 and PGF2 alpha have a potent central antisecretory action in conscious, pylorus-ligated rats, whereas arachidonic acid, PGD2 and PGI2 do not have any central effects on gastric secretion. It is suggested that PGE2 and PGF2 alpha may be involved in the central nervous system control of gastric secretion. PMID:6360279

Puurunen, J.

1983-01-01

154

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

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.

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

155

Prune-belly syndrome: case series and review of the literature regarding early prenatal diagnosis, epidemiology, genetic factors, treatment, and prognosis.  

PubMed

Prune-belly syndrome (PBS) is a rare congenital syndrome characterized by deficient abdominal muscles, urinary tract malformation, and in males, cryptorchidism and has an estimated incidence of 1 in 35,000 to 1 in 50,000 live births. The syndrome might be due to severe bladder outlet obstruction or to abdominal muscle deficiency secondary to a migrational defect of the lateral mesoblast between weeks 6 and 7 of pregnancy. The current review of the medical record reports a special focus on epidemiology, genetic factors, early prenatal diagnosis clusters, treatment, and prognosis of PBS. PMID:22506933

Tonni, Gabriele; Ida, Vito; Alessandro, Ventura; Bonasoni, Maria Paola

2013-02-01

156

Genetics  

NSDL National Science Digital Library

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

Doherty, Jennifer; Waldron, Ingrid; Poethig, Scott

157

Genetics  

MedlinePLUS

... made up of strands of genetic information called DNA. Genes are sections of DNA. The location of the gene is called the ... differences occur in less than 1% of the DNA sequence and produce variants of a particular gene ...

158

Führt uns die Präimplantationsdiagnostik auf eine Schiefe Ebene?  

Microsoft Academic Search

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

Christian Netzer

1998-01-01

159

Genetics  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

160

Genetic technology: Promises and problems  

NASA Technical Reports Server (NTRS)

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.

Frankel, M. S.

1975-01-01

161

Genetic characterization of Epimedium species using random amplified polymorphic DNA (RAPD) and PCR-restriction fragment length polymorphism (RFLP) diagnosis.  

PubMed

Total DNA was extracted from the leaves of seven Epimedium species grown in different places in Japan. Their genetic characterization was performed by DNA analyses of random amplified polymorphic DNA (RAPD) using 32 random primers having 10 base sequences, and by restriction fragment length polymorphism (RFLP). E. sagittatum and E. koreanum were easily distinguished by a representative amplified band pattern. It became evident that E. sagittatum had extremely different genetic composition compared to the other species. A dendrogram obtained from the similarity matrix by cluster analysis indicates that E. sagittatum can be completely isolated from the other species. Moreover, it became evident that E. grandiflorum var. higoense, E. trifoliatobinatum and E. koreanum are independent species, contrary to the previous assumption that they are subspecies or a variety. The geographical variation of E. sempervirens was confirmed by cluster analysis. E. diphyllum showed wide genetic variations, in spite of sampling from the same area. PMID:8820914

Nakai, R; Shoyama, Y; Shiraishi, S

1996-01-01

162

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

Microsoft Academic Search

Background  Primary hyperoxaluria type I (PH1) is a rare genetic disorder characterized by allelic and clinical heterogeneity. Four mutations\\u000a (G170R, 33_34insC, I244T and F152I) account for more than 50% of PH1 alleles and form the basis for diagnostic genetic screening\\u000a for PH1. We aimed to analyze the prevalence of these specific mutations causing PH1, and to provide an accurate tool for

Ibtihel Benhaj Mbarek; Saoussen Abroug; Asma Omezzine; Dorsaf Zellama; Abdellatif Achour; Abdelaziz Harbi; Ali Bouslama

2011-01-01

163

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

ERIC Educational Resources Information Center

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…

Moss, J.; Howlin, P.

2009-01-01

164

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

ERIC Educational Resources Information Center

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…

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

2011-01-01

165

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

Microsoft Academic Search

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

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

1989-01-01

166

Barren promise : the hope and heartache in treating infertility  

E-print Network

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

McDonough, Maureen (Maureen Ann)

2005-01-01

167

Genetics  

NSDL National Science Digital Library

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

Goodfellow, Miss

2007-10-23

168

Genetics  

NSDL National Science Digital Library

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

The Tech Museum of Innovation

2004-01-01

169

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

PubMed Central

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

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

2009-01-01

170

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

PubMed Central

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

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

2013-01-01

171

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

PubMed Central

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

2014-01-01

172

[Andersen-Tawil syndrome: A review of its clinical and genetic diagnosis with emphasis on cardiac manifestations].  

PubMed

The Andersen-Tawil syndrome is a cardiac ion channel disease that is inherited in an autosomal dominant way and is classified as type 7 of the congenital long QT syndromes. Affected gene is KCNJ2, which forms the inward rectifier potassium channel designated Kir2.1. This protein is involved in stabilizing the resting membrane potential and controls the duration of the action potential in skeletal muscle and heart. It also participates in the terminal repolarization phase of the action potential in ventricular myocytes and is a major component responsible for the correction in the potassium current during phase 3 of the action potential repolarization. Kir 2.1 channel has a predominant role in skeletal muscle, heart and brain. Alterations in this channel produce flaccid paralysis, arrhythmias, impaired skeletal development primarily in extremities and facial area. In this review we address the disease from the point of view of clinical and molecular diagnosis with emphasis on cardiac manifestations. PMID:25270337

Márquez, Manlio F; Totomoch-Serra, Armando; Vargas-Alarcón, Gilberto; Cruz-Robles, David; Pellizzon, Oscar A; Cárdenas, Manuel

2014-01-01

173

Twisting the night away: a review of the neurobiology, genetics, diagnosis, and treatment of shift work disorder.  

PubMed

Although not all individuals who work outside of standard daytime hours develop physical and psychiatric issues, there is a substantial portion of shift workers who develop shift work disorder. Shift work disorder is due to a misalignment between an individual's endogenous circadian rhythms and environmental stimuli, and can have potentially serious consequences to an individual's health and quality of life. This article reviews the neurobiological and genetic underpinnings of shift work disorder, and describes how desynchronization of the molecular clock may lead to both physical and psychiatric illnesses. Diagnostic tools and treatment guidelines to address the circadian misalignment, excessive sleepiness, and insomnia experienced by patients with shift work disorder are also discussed. PMID:24345709

Morrissette, Debbi Ann

2013-12-01

174

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

PubMed

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

Marinakis, Yannis; Dounias, Georgios; Jantzen, Jan

2009-01-01

175

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

PubMed Central

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

MAO, GANG; LIU, LEI

2014-01-01

176

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

PubMed

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

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

2015-02-01

177

Genetic variation of porcine circovirus type 2 (PCV2) and its relevance to vaccination, pathogenesis and diagnosis.  

PubMed

Porcine circovirus-associated disease (PCVAD) encompasses a group of complex, multi-factorial syndromes, which are dependent on infection with porcine circovirus type 2 (PCV2). Current strains of PCV2 circulating in the field are classified into two groups, termed PCV2a and PCV2b. Outbreaks of severe PCVAD in North America and other countries are often linked to a shift from PCV2a to PCV2b as the predominant genotype. Therefore, genotype-specific differences in pathogenesis and antigenicity have been suggested. Overall, evidence suggests that virulence is a function of the specific PCV2 isolate, regardless of genotype. In addition, only minor antigenic differences have been reported. In terms of immunopathogenesis, a conserved decoy epitope, located in the C-terminal region of the capsid protein, provides an explanation for the inability to identify pathogenic differences between genotypes. Finally, genetic variation in PCV2 and the resulting consequences with respect to vaccination and diagnostics are discussed. PMID:22198217

Trible, Benjamin R; Rowland, Raymond R R

2012-03-01

178

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

Microsoft Academic Search

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

DANIEL DYKHUIZEN; DANIEL L. HARTL

1980-01-01

179

Genetics Home Reference: Vitiligo  

MedlinePLUS

... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Vitiligo On this page: Description Genetic changes Inheritance Diagnosis ... information Glossary definitions Reviewed December 2010 What is vitiligo? Vitiligo is a condition that causes patchy changes ...

180

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 ...

181

Genetics Home Reference: Hemophilia  

MedlinePLUS

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

182

Genetics Home Reference: Achondroplasia  

MedlinePLUS

... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Achondroplasia On this page: Description Genetic changes Inheritance Diagnosis ... names Glossary definitions Reviewed May 2012 What is achondroplasia? Achondroplasia is a form of short-limbed dwarfism. ...

183

Complex Multi-Block Analysis Identifies New Immunologic and Genetic Disease Progression Patterns Associated with the Residual ?-Cell Function 1 Year after Diagnosis of Type 1 Diabetes  

PubMed Central

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

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

2013-01-01

184

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

PubMed

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

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

2015-01-20

185

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

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

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

2004-01-01

186

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 August 2007 What is breast cancer? Breast cancer is a disease in which certain ...

187

Genetics Home Reference: Meige lymphedema  

MedlinePLUS

... Recent literature OMIM Genetic disorder catalog Conditions > Meige lymphedema On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed November 2010 What is Meige lymphedema? Meige lymphedema is a condition that affects the ...

188

Genetics Home Reference: Down syndrome  

MedlinePLUS

... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Down syndrome On this page: Description Genetic changes Inheritance Diagnosis ... names Glossary definitions Reviewed June 2012 What is Down syndrome? Down syndrome is a chromosomal condition that is ...

189

Genetics Home Reference: Blau syndrome  

MedlinePLUS

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

190

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

PubMed Central

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

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

2005-01-01

191

Arlequin based PGD domain decomposition  

NASA Astrophysics Data System (ADS)

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

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

2014-11-01

192

Genetics Home Reference: Type A insulin resistance syndrome  

MedlinePLUS

... OMIM Genetic disorder catalog Conditions > Type A insulin resistance syndrome On this page: Description Genetic changes Inheritance Diagnosis Additional information Other names Glossary definitions ...

193

Ante-mortem diagnosis, diarrhea, oocyst shedding, treatment, isolation, and genetic typing of Toxoplasma gondii associated with clinical toxoplasmosis in a naturally infected cat.  

PubMed

Toxoplasma gondii infections are common in humans and other animals, but clinical disease is relatively rare. It is unknown whether the severity of toxoplasmosis in immunocompetent hosts is due to the parasite strain, host variability, or to other factors. Recently, attention has been focused on the genetic variability among T. gondii isolates from apparently healthy and sick hosts. Whether T. gondii genetic makeup plays a part in the pathogenesis of clinical feline toxoplasmosis is uncertain because little is known of genetic typing of strains associated with clinical feline toxoplasmosis. A 6-mo-old domestic male cat was hospitalized because of lethargy, anorexia, fever, and diarrhea. Numerous (6 million in 1 sample) T. gondii oocysts were found in feces of the cat and antibodies to T. gondii (titer 1:800) were found in its serum by the modified agglutination test. The cat was medicated orally with Clindamycin for 10 days; it became asymptomatic after 10 days and was discharged from the hospital. Viable T. gondii (designated TgCatUs9) was isolated from feces (oocysts) by bioassays in mice. Genetic typing using the DNA extracted from the brains of infected mice and 10 PCR-restriction fragment length polymorphism (RFLP) markers revealed Type II allele at the SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, and PK1 loci and Type I at the L358 and Apico loci; therefore, this isolate belongs to the ToxoDB PCR-RFLP genotype no. 4, which is grouped into the Type 12 lineage that is dominant in wildlife from North America. To our knowledge, this is the first T. gondii isolate characterized genetically from a sick cat in the USA. PMID:22924914

Dubey, J P; Prowell, M

2013-02-01

194

Genomic medicine for cancer diagnosis.  

PubMed

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. J. Surg. Oncol. 2015 111:24-30. © 2014 Wiley Periodicals, Inc. PMID:25346009

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

2015-01-01

195

Hb Manukau [?67(E11)Val???Gly; HBB: c.203T>G]: the role of genetic testing in the diagnosis of idiopathic hemolytic anemia.  

PubMed

The increasing availability of DNA sequencing of globin genes has improved our ability to detect conditions that were presumed to be extremely rare. These conditions may remain undiagnosed due to unfamiliarity with clinical presentation, relative unavailability of advanced diagnostic alternatives, or may defy detection by being electrophoretically silent or extreme instability rendering their presence to be below detection level. Genetic studies were pursued in a mother and daughter with severe hemolytic anemia as initial testing failed to be diagnostic. DNA sequence analysis of the ?-globin gene identified Hb Manukau [?67(E11)Val???Gly; HBB: c.203T?>?G], an extremely unstable hemoglobin (Hb) variant. This is the second family described with this condition (first in the western hemisphere). An astute clinician may benefit from being persistent and pursuing additional testing including molecular genetic characterization where clinical suspicion remains high. PMID:24611675

Kumar, Mudra Kohli; Judd, Courtney; Hoyer, James D; Swanson, Kenneth C; Nelson, Linda; Oliveira, Jennifer L

2014-01-01

196

Frontotemporal Dementia: Genetics  

MedlinePLUS

Genetics of FTD After receiving a diagnosis of FTD in a family member, one of the first questions many people have is: Are other members ... Understanding the Genetics of FTD: A guide for patients and their families . You can download the booklet ...

197

Canine molecular genetic testing.  

PubMed

Inherited diseases are common among dogs. Recent advances in molecular genetics provide the groundwork for the development of genetic tests for the diagnosis and prevention of inherited diseases. As a result of this progress, genetics should become an integral part of veterinary medicine. DNA tests are safe, easy to perform, and reliable if interpreted correctly. Genetic tests only need to be performed once in a dog's lifetime, because the results of DNA testing never change. Veterinarians should be prepared to understand genetic testing and counseling because they are becoming increasingly important to veterinary medicine. PMID:11265501

Metallinos, D L

2001-03-01

198

Methylamine accumulation in cultured cells as a measure of the aqueous storage compartment in the laboratory diagnosis of genetic lysosomal diseases.  

PubMed

Intracellular accumulation of the lysosomotropic compound [14C]methylamine was used to estimate the size of the lysosomal compartment in fibroblasts cultured from patients with a variety of lysosomal storage diseases. In previous work from our laboratory, it was shown that methylamine accumulation was significantly increased in diseases with infantile or juvenile onset and storage of predominantly water-soluble material such as in the mucopolysaccharidoses, mucolipidoses, and oligosaccharidoses. In the present study, methylamine incorporation was abnormally increased in cells from patients with glycogenosis type II and with Niemann-Pick type C disease, whereas it was normal in other sphingolipidoses and in the late-infantile and juvenile forms of neuronal ceroid lipofuscinoses. The methylamine test was also checked regarding its potential use for prenatal diagnostic testing. In model systems with cultured amniotic or chorionic villus cells, lysosomal storage was experimentally induced by the cathepsin inhibitor leupeptin and was readily detected when compared to untreated controls. Cultured amniotic cells from a fetus with mucopolysaccharidosis II were found to incorporate significantly higher amounts of [14C]methylamine than the normal controls. The results indicate that the methylamine accumulation method is an additional tool in the diagnosis and prenatal diagnosis of lysosomal diseases with abnormal storage of water-soluble material. PMID:8723110

Kopitz, J; Harzer, K; Kohlschütter, A; Zöller, B; Blenck, N; Cantz, M

1996-05-01

199

Autoinflammatory syndromes: diagnosis and management  

Microsoft Academic Search

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

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

2010-01-01

200

Genetics Home Reference: Y chromosome infertility  

MedlinePLUS

... literature OMIM Genetic disorder catalog Conditions > Y chromosome infertility On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed January 2009 What is Y chromosome infertility? Y chromosome infertility is a condition that affects ...

201

Genetics Home Reference: Spastic paraplegia type 11  

MedlinePLUS

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

202

Genetics and Medicine: An Evolving Relationship  

ERIC Educational Resources Information Center

Described is the importance of genetic factors in health and disease and calls for the development of services for genetic screening, diagnosis, and counseling. Such services presently available in Canada are described. (BB)

Scriver, Charles R.; And Others

1978-01-01

203

Genetics Home Reference: Intrahepatic cholestasis of pregnancy  

MedlinePLUS

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

204

Genetics Home Reference: Spastic paraplegia type 4  

MedlinePLUS

... OMIM Genetic disorder catalog Conditions > Spastic paraplegia type 4 On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed January 2008 What is spastic paraplegia type 4? Spastic paraplegia type 4 is part of a ...

205

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 ...

206

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 ...

207

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

PubMed Central

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

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

2015-01-01

208

Fault diagnosis  

NASA Technical Reports Server (NTRS)

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.

Abbott, Kathy

1990-01-01

209

Epstein-Barr virus-induced transformation of B cells for the diagnosis of genetic metabolic disorders--enumerative conditions for cryopreservation.  

PubMed

Epstein-Barr virus (EBV) infection in vitro causes transformation of B cells and generates B lymphoblastoid cell lines (LCLs). These LCLs have been widely used for the diagnostic of several genetic metabolic disorders. However, up to now, efficiency of LCL generation has been based on misleading subjective analysis. In this study, quantitative analyses have been performed to indicate efficiency of B-cell transformation to measuring human lysosomal acid hydrolases associated with: GM1-gangliosidosis type I, Gaucher disease and mucopolysaccharidosis type I. Peripheral blood mononuclear cells were isolated from 13 subjects, and LCLs were produced by culturing them with EBV for 12 days. Activities of the enzymes beta-galactosidase, beta-glucosidase and alpha-iduronidase were measured before and after cryopreservation in liquid nitrogen for 30 days. Efficiency of the B-cell transformation was screened every 4 days by the enumeration of cell proliferation, cell counts and changes in granularity estimated by flow cytometry. We observed the generation of 13 LCLs. Cell transformation was confirmed by the gradual increase of cellular clusters, cell size and granularity. In addition, we determined that the activity of the enzymes mentioned above did not change following cryopreservation. These data suggest that our enumerative approach for screening of EBV-LCLs is efficient for the enzymatic determination of human lysosomal acid hydrolases and may thus replace misleading subjective analyses. PMID:16426420

Mello, A S; Burin, M G; Michellin, K; Viapiana, M; Giugliani, R; Coelho, J C; Bauer, M E

2006-02-01

210

Modern diagnosis and management of the porphyrias.  

PubMed

Recent advances in the molecular understanding of the porphyrias now offer specific diagnosis and precise definition of the types of genetic mutations involved in the disease. Molecular diagnostic testing is powerful and very useful in kindred evaluation and genetic counselling when a disease-responsible mutation has been identified in the family. It is also the only way to properly screen asymptomatic gene carriers, facilitating correct treatment and appropriate genetic counselling of family members at risk. However, it should be noted that DNA-based testing is for the diagnosis of the gene carrier status, but not for the diagnosis of clinical syndrome or severity of the disease, e.g. an acute attack. For the diagnosis of clinically expressed porphyrias, a logical stepwise approach including the analysis of porphyrins and their precursors should not be underestimated, as it is still very useful, and is often the best from the cost-effective point of view. PMID:16956347

Sassa, Shigeru

2006-11-01

211

Genetic Analysis of Isozyme Loci in Tetraploid Potatoes ( SOLANUM TUBEROSUM L.)  

PubMed Central

The genetic control of eight isozyme loci revealed by starch gel electrophoresis was studied through the analysis of three progenies derived from four tetraploid cultivars of Solanum tuberosum (groups Andigena and Tuberosum). Duplicate gene expression was found in seven (Got-A, Got-B, Pgd-C, Pgi-B, Pgm-A, Pgm-B and Pox-C) isozyme loci. In another isozyme gene (Adh-A), the parental genotypes were not adequate to distinguish between a monogenic or a digenic model of genetic control. Tetrasomic inheritance was demonstrated in four (Got-A, Got-B, Pgd-C and Pgi-B) isozyme loci. In the remaining duplicate genes, the parental genotypes precluded discrimination between disomic or tetrasomic models. Tetrasomic segregations of the chromosomal type were generally found; however, the isozyme phenotypes shown by three descendants from selfing cv. Katahdin indicate the occurrence of chromatid segregations, although aneuploidy cannot be ruled out. Either autoploidy or amphidiploidy with lack of chromosome differentiation between the two diploid ancestors can account for the existence of tetrasomic inheritance in the common potato. PMID:17246238

Martinez-Zapater, J. M.; Oliver, Jose L.

1984-01-01

212

Polyunsaturated fatty acid metabolites as novel lipidomic biomarkers for noninvasive diagnosis of nonalcoholic steatohepatitis.  

PubMed

Lipotoxicity is a key mechanism thought to be responsible for the progression of nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). Noninvasive diagnosis of NASH is a major unmet clinical need, and we hypothesized that PUFA metabolites, in particular arachidonic acid (AA)-derived eicosanoids, in plasma would differentiate patients with NAFL from those with NASH. Therefore, we aimed to assess the differences in the plasma eicosanoid lipidomic profile between patients with biopsy-proven NAFL versus NASH versus normal controls without nonalcoholic fatty liver disease (NAFLD; based on MRI fat fraction <5%). We carried out a cross-sectional analysis of a prospective nested case-control study including 10 patients with biopsy-proven NAFL, 9 patients with biopsy-proven NASH, and 10 non-NAFLD MRI-phenotyped normal controls. We quantitatively compared plasma eicosanoid and other PUFA metabolite levels between NAFL versus NASH versus normal controls. Utilizing a uniquely well-characterized cohort, we demonstrated that plasma eicosanoid and other PUFA metabolite profiling can differentiate between NAFL and NASH. The top candidate as a single biomarker for differentiating NAFL from NASH was 11,12-dihydroxy-eicosatrienoic acid (11,12-diHETrE) with an area under the receiver operating characteristic curve (AUROC) of 1. In addition, we also found a panel including 13,14-dihydro-15-keto prostaglandin D2 (dhk PGD2) and 20-carboxy arachidonic acid (20-COOH AA) that demonstrated an AUROC of 1. This proof-of-concept study provides early evidence that 11,12-diHETrE, dhk PGD2, and 20-COOH AA are the leading eicosanoid candidate biomarkers for the noninvasive diagnosis of NASH. PMID:25404585

Loomba, Rohit; Quehenberger, Oswald; Armando, Aaron; Dennis, Edward A

2015-01-01

213

Genetics Home Reference: Trichohepatoenteric syndrome  

MedlinePLUS

... that occurs multiple times per day. Even with nutritional support through intravenous feedings (parenteral nutrition), many of these ... Genetic Testing Registry: Trichohepatoenteric syndrome 2 Health Topic: Nutritional Support You might also find information on the diagnosis ...

214

Genetics Home Reference: Metachromatic leukodystrophy  

MedlinePLUS

... may be useful. Genetics and Health Resources for Patients and Families Resources for Health Professionals What glossary definitions help with understanding metachromatic leukodystrophy? autosomal ; autosomal recessive ; cell ; central nervous system ; deficiency ; diagnosis ; enzyme ; gait ; gallbladder ; gene ; ...

215

Genetics Home Reference: Gillespie syndrome  

MedlinePLUS

... Disabilities? Genetic Testing Registry: Aniridia, cerebellar ataxia, and mental retardation You might also find information on the diagnosis ... use for Gillespie syndrome? aniridia, cerebellar ataxia, and mental retardation aniridia-cerebellar ataxia-intellectual disability aniridia-cerebellar ataxia- ...

216

Cancer diagnosis.  

PubMed

Essential facts Around 300,000 people were diagnosed with cancer in England and Wales in 2011, and more than one in three people in the UK will develop cancer in some form during their lifetime. An early diagnosis is the best way to tackle the disease and improve survival rates. However, not enough is being done to identify cancer and treat it an early stage, says the National Institute for Health and Care Excellence (NICE). PMID:25605088

2015-01-21

217

Melanoma Diagnosis  

NASA Astrophysics Data System (ADS)

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

Horsch, Alexander

218

Prenatal diagnosis of cystic fibrosis.  

PubMed

Cystic fibrosis is the most common autosomal recessive genetic disorder in the Caucasian population (1:2000-1:4000) (Warwick, W. J. (1978) Helv. Paediatr. Acta 33, 117-125). This defect is characterized by chronic obstructive pulmonary disease, pancreatic exocrine insufficiency and abnormally high perspiration electrolytes in most patients (Talamo et al. (1985) In: The metabolic basis of inherited diseases, pp. 1887-1917). The elevated electrolyte level provides the most reliable diagnostic test for cystic fibrosis homozygotes. Although prospects for cystic fibrosis patients have improved, genetically homozygous cystic fibrosis is effectively a lethal disease. Because of the seriousness of the disease, many families with one affected child desire a prenatal diagnosis when a second pregnancy occurs. Despite extensive research, the biochemical basis of cystic fibrosis remains unknown. Secondary effects on microvillar enzymes allow second trimester diagnosis (17-18 weeks of gestation (Brock, D. H. J. (1983) Lancet II, 941-943). First trimester prenatal diagnosis for cystic fibrosis became possible with DNA technology. Application of polymorphic marker loci to problems of prenatal diagnosis and carrier-testing is discussed. PMID:2651551

Kampmann, W; Mathy, L; Grzeschik, K H; Driesel, A j; Bartholomé, K; Neugebauer, M; Olek, K

1989-03-01

219

Genetic Technologies and Ethics  

Microsoft Academic Search

In the past decade, the human genome has been completely sequenced and the know- ledge from it has begun to influence the fields of biological and social sciences in fundamental ways. Identification of about 25000 genes in the human genome is expected to create great benefits in diagnosis and treatment of diseases in the coming years. However, Genetic technologies have

Ali M. Ardekani

220

[Medical genetics and the genome.  

PubMed

Next generation sequencing, a remarkable progress in medical genetics, analyses the exome for disease-causing mutations (exome sequencing) especially in cases with genetic heterogeneity or cases where single gene approach has not revealed the diagnosis. Many unsolved questions exist such as unsolicited findings in genes not related to the patients' symptoms or variants of unknown significance. Informed consent is crucial before analysis but post-test genetic counselling and strategies for reporting back results to family members are necessary. PMID:25394930

Gerdes, Anne-Marie; Vogel, Ida

2014-11-10

221

[Genetic analysis].  

PubMed

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

Morishita, Eriko

2014-07-01

222

[Pheochromocytoma: diagnosis and treatment].  

PubMed

Pheochromocytoma (pheo) is adrenal or less frequently extraadrenal tumour of chromafine tissue. Pheos are rare, but cardiovascular and metabolic abnormalities are common. Unrecognised pheo may lead to fatal hypertensive crisis during anesthesia or other stresses. Proper diagnosis of pheo is thus of utmost importance. 24-h blood pressure (BP) monitoring may contribute to the diagnosis of pheo due to increased BP variability and absence of night BP decline. Pheo contains large amount of enzyme catechol-O-methyl transpherase (COMT) with subsequent excessive production of COMT metabolites like metanephrines. Measurement of plasma free metanephrines or urinary fraccionated metanephrines has usually higher sensivitivity and specificity compared with plasma or urinary catecholamines. Morphological diagnosis of adrenal/extraadrenal pheo is based on CT/MR visualisation and 123I-metaiodobenzylguanidin (MIBG) or PET 18F-fluorodeoxyglucose scan. Genetic analysis should be performed in all confirmed pheo cases, especially in younger subjects below 50 years of age in order to detect mutations of following genes: von Hippel-Lindau (VHL), RET- protooncogen, genes encoding B, C and D subunit of mitochondrial sukcinat dehydrogenaze (SDHB, SDHC, SDHD) and neurofibromatosis type I gene. Pharmacological treatment is based on alpha blockers with subsequent (after 24-48 hours) administration of beta-blockers/especially in patients with tendency to tachycardia/. Following this therapy normalisation of BP is common and laparoscopic excision of pheo tumour can be realised. Malignant pheos are difficult to treat due to early occurrence of metastasis and lack of response to chemotherapy or iradiation in most cases. PMID:19899721

Widimský, J; Zelinka, T; Petrák, O; Strauch, B; Rosa, J; Michalský, M; Kasalický, M; Safarík, L; Vranková, A; Holaj, R

2009-01-01

223

Genetics in the art and art in genetics.  

PubMed

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

Bukvic, Nenad; Elling, John W

2015-01-15

224

Genetics Home Reference: Sensorineural deafness and male infertility  

MedlinePLUS

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

225

Genetics Home Reference: CATSPER1-related nonsyndromic male infertility  

MedlinePLUS

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

226

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 ...

227

Genetics Home Reference: Leukoencephalopathy with vanishing white matter  

MedlinePLUS

... Genetic disorder catalog Conditions > Leukoencephalopathy with vanishing white matter On this page: Description Genetic changes Inheritance Diagnosis ... May 2013 What is leukoencephalopathy with vanishing white matter? Leukoencephalopathy with vanishing white matter is a progressive ...

228

Genetics Home Reference: Hereditary sensory neuropathy type 1  

MedlinePLUS

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

229

Genetics Home Reference: GRN-related frontotemporal dementia  

MedlinePLUS

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

230

Genetic counseling services and development of training programs in Malaysia.  

PubMed

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

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

2013-12-01

231

New Genetics  

MedlinePLUS

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

232

Genetic Counseling  

MedlinePLUS

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

233

Medical genetics  

SciTech Connect

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.

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

1989-01-01

234

Diagnosis and evaluation of hypogonadism.  

PubMed

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

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

2014-02-01

235

Down syndrome in India--diagnosis, screening, and prenatal diagnosis.  

PubMed

Down syndrome (DS) is the most common genetic cause of mental retardation. Clinical manifestations are variable, and children have psychomotor impairment, multiple malformations, and medical conditions. Confirmation of the diagnosis is by karyotype analysis. The cytogenetic abnormality can be classified into pure trisomy 21, translocation, or mosaicism. Risk of recurrence depends on the primary cytogenetic abnormality in the proband. Prenatal screening is by biochemical and ultrasound markers in the first and second trimester. Definitive prenatal diagnosis is by analysis of fetal chromosomes in fetal chorionic villi, amniocytes, or cord blood. A noninvasive test for trisomy 21 in maternal blood has been developed by massively parallel shotgun sequencing. Therapeutic studies in Ts65Dn mice suggest an exciting prospect of improvement of learning ability and memory deficits. PMID:22727002

Verma, Ishwar C; Lall, Meena; Dua Puri, Ratna

2012-06-01

236

Polycystic ovary syndrome—diagnosis and etiology  

Microsoft Academic Search

Polycystic ovary syndrome (PCOS) is a heterogenous condition with signs and symptoms including menstrual dysfunction, weight disorders, hirsutism, acne, endometrial hyperplasia, diabetes mellitus, metabolic syndrome and hyperlipidemia. As such, diagnosis is controversial and differs between countries and communities. By consensus, recent definitions highlight ovarian morphology, hyperandrogenism and menstrual dysfunction. Etiology is undetermined and may include genetic and environmental aspects, including

R. J Norman; T Hickey; L Moran; J Boyle; J Wang; M Davies

2004-01-01

237

The diagnosis of mitochondrial muscle disease  

Microsoft Academic Search

Mitochondrial respiratory chain abnormalities are an important cause of neuromuscular disease and may be due to defects of either the mitochondrial or nuclear genome. On account of the clinical and genetic heterogeneity exhibited by the mitochondrial myopathies, their investigation and diagnosis remains a challenge, requiring a combination of techniques including muscle histochemistry, biochemical assessment of respiratory chain function and molecular

Robert W. Taylor; Andrew M. Schaefer; Martin J. Barron; Robert McFarland; Douglass M. Turnbull

2004-01-01

238

[Genetic differentiation of the Mongolian population. Comparative analysis of the geographic distribution of biochemical markers of genes and restriction fragment length polymorphism of nuclear DNA in the Mongolian population].  

PubMed

The geographical distribution of the gene frequencies from loci: Hp, Tf, Gc, Pi, AcP1, GLO1, EsD, 6-PGD, PGM1 and RFLP's of the nuclear DNA of the loci HBG-2 (HindIII), HBB (AvaII), ApoB (XbaI), D7S8 (PstI), LDLR (HincII) and AT-3 was analysed in the Mongolian population. These data revealed the homogeneity of 18 local groups in Mongolia and extremely low genetic differences measured by GST. There was no differences in the average GST values between protein markers and nuclear DNA markers. PMID:1361922

Sambuugi?n, N; Rychkov, Iu G; Petrishchev, V N; Shne?der, Iu V

1992-09-01

239

On the Intelligent Fault Diagnosis Method for Marine Diesel Engine  

Microsoft Academic Search

The marine diesel engine is a complex system. Its mapping process of fault diagnosis has multi-fault attributes, which means input and output of fault pattern attribute are the multi-mapping relations. An approach of intelligent fault diagnosis using fuzzy neural networks and genetic algorithms to optimize and train is studied in this paper for this system. The structure and the model

Peng Li; Baoku Su

2008-01-01

240

Equipment fault diagnosis algorithm of SVM based on GA  

Microsoft Academic Search

To solve the problem of equipment fault diagnosis, the paper proposes a fault diagnosis model based on Support Vector Machines (SVM) and studies the parameters that influence model accuracy. On the basis of analyzing model parameters influence, A new kind of evaluation function about algorithm accuracy and the Genetic algorithm of the global optimization parameters selection are presented. According to

Xiaoli Cao; Chao-yuan Jiang; Siyuan Gan

2010-01-01

241

Genetic counseling  

E-print Network

GENETIC COUNSELING What Is Genetic Counseling? The National Society of Genetic Counselors (NSGC) defines genetic counseling as the process of assisting people with understanding and adapting to the medical, psychological, and familial implications... of genetic contributions to disease (National Society of Genetic Counselors, 2012). This process includes the interpreta- tion of family and medical histories to assess the chance of disease occurrence or recurrence. Genetic counseling usually involves...

Stough, Laura

2014-01-01

242

[Genetics of hypophosphatasia].  

PubMed

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

Mornet, E; Simon-Bouy, B

2004-05-01

243

Osteogenesis imperfecta: diagnosis and treatment.  

PubMed

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

Biggin, A; Munns, C F

2014-09-01

244

Genetics Home Reference: Congenital hepatic fibrosis  

MedlinePLUS

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

245

Genetic algorithms  

NASA Technical Reports Server (NTRS)

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

Wang, Lui; Bayer, Steven E.

1991-01-01

246

PGD in 47,XXY Klinefelter's syndrome patients  

Microsoft Academic Search

The use of ICSI has been a major breakthrough in the treatment of male infertility. Even azoospermic patients with focal spermatogenesis in the testis, may benefit from the ICSI technique in order to father a child. As ICSI use has become more common, centres have introduced infertility treatment for Klinefelter patients. To date, 34 healthy children have been born using

C. Staessen; H. Tournaye; E. Van Assche; A. Michiels; L. Van Landuyt; P. Devroey; I. Liebaers; A. Van Steirteghem

2003-01-01

247

Craniosynostosis genetics: The mystery unfolds  

PubMed Central

Craniosynsostosis syndromes exhibit considerable phenotypic and genetic heterogeneity. Sagittal synostosis is common form of isolated craniosynostosis. The sutures involved, the shape of the skull and associated malformations give a clue to the specific diagnosis. Crouzon syndrome is one of the most common of the craniosynostosis syndromes. Apert syndrome accounts for 4.5% of all craniosynostoses and is one of the most serious of these syndromes. Most syndromic craniosynostosis require multidisciplinary management. The following review provides a brief appraisal of the various genes involved in craniosynostosis syndromes, and an approach to diagnosis and genetic counseling. PMID:22090712

Panigrahi, Inusha

2011-01-01

248

Predicting violence: nursing diagnosis versus psychiatric diagnosis.  

PubMed

Predicting violent behavior is a major concern for nurses as well as other mental health professionals. Two diagnostic assessment systems (Nursing Diagnosis-NANDA and Psychiatric Diagnosis-DSM III-R) were compared in their ability to predict assaultive behavior. The nursing diagnosis potential for violence suggested a difference (p = .07) between the assaultive and control subjects. No differences were found between assaultive and control subjects on psychiatric diagnoses. Nursing diagnosis is based upon measurable behaviors and is time specific. Clinical implications and further research endeavors in this area are suggested. PMID:7826718

Lanza, M L; Kayne, H L; Pattison, I; Hicks, C; Islam, S

1994-01-01

249

Microcomputer based differential diagnosis of dysmorphic syndromes.  

PubMed

Dysmorphic syndromes are characterized by associations of physical abnormalities depending in its diagnosis on the recognition of a particular pattern. Because of their multiplicity, the rarity of some of them, and the frequency of new reports, computerized data bases have proved useful as powerful tools assisting in the differential diagnosis. The role of artificial intelligence methods, in particular Expert Systems, as promising tools in helping physicians to perform a clinical diagnosis is underlined. Using a high level computer language presently used in the artificial intelligence field (Prolog), a microcomputer based system for the differential diagnosis of dysmorphic syndromes is described. Its capabilities and simplicity of use, derived from an efficient and attractive computer interface, are underlined. The need of performance assessment by evaluating its accuracy and usefulness before its introduction into genetic clinical practice is stressed. Finally, for the completeness of the knowledge base, the need of cooperation between international centers is emphasized. PMID:2662096

Veloso, M L; Feijóo, M J

1989-03-01

250

Genetic association studies in ?-hemoglobinopathies.  

PubMed

Characterization of the molecular basis of the ?-thalassemias and sickle cell disease (SCD) clearly showed that individuals with the same ?-globin genotypes can have extremely diverse clinical severity. Two key modifiers, an innate ability to produce fetal hemoglobin and coinheritance of ?-thalassemia, both derived from family and population studies, affect the pathophysiology of both disorders at the primary level. In the past 2 decades, scientific research had applied genetic approaches to identify additional genetic modifiers. The review summarizes recent genetic studies and key genetic modifiers identified and traces the story of fetal hemoglobin genetics, which has led to an emerging network of globin gene regulation. The discoveries have provided insights on new targets for therapeutic intervention and raise possibilities of developing fetal hemoglobin predictive diagnostics for predicting disease severity in the newborn and for integration into prenatal diagnosis to better inform genetic counseling. PMID:24319204

Thein, Swee Lay

2013-01-01

251

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. ...

252

Genetic Algorithms  

Microsoft Academic Search

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.

Kumara Sastry; David Goldberg; Graham Kendall

253

Human embryonic stem cell lines derived from single blastomeres  

Microsoft Academic Search

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

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

2006-01-01

254

Symbiotic relationships: saviour siblings, family rights and biomedicine.  

PubMed

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

Bennett, Belinda

2005-12-01

255

Selection of the most common chromosome abnormalities in oocytes prior to ICSI  

Microsoft Academic Search

So far, all preimplantation genetic diagnosis (PGD) protocols in use produce results after the eggs have been fertilized. However, these approaches are not acceptable for patients with moral objections to the generation and discard of supernumerary zygotes or embryos. In these circumstances, only those oocytes to be replaced may be inseminated. The purpose of this study was to develop a

Santiago Munné; Soledad Sepulveda; Jose Balmaceda; Emilio Fernandez; Cecilia Fabres; Antonio Mackenna; Teresa Lopez; Javier A. Crosby

2000-01-01

256

Designing babies: what the future holds  

Microsoft Academic Search

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

Yury Verlinsky

2005-01-01

257

BREAST CANCER DETECTION USING GENETIC PROGRAMMING  

E-print Network

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

Fernandez, Thomas

258

Access, quality and costs of prenatal diagnosis.  

PubMed

The background risk of birth defects ranges from 2 to 5%. These birth defects are responsible for 30% of all admissions to pediatric hospitals and are responsible for a large proportion of neonatal and infant deaths. Medicine and Genetics have taken giant steps in their ability to detect and treat genetic disorders in utero. Screening tests for prenatal diagnosis should be offered to all pregnant women to assess their risk of having a baby with a birth defect or genetic disorder. Psychosocial and financial factors, inadequate insurance coverage, and the inability to pay for health care services are some of the known barriers to healthcare. These barriers are particularly magnified when there is a language barrier. From an economical standpoint it has been demonstrated that prenatal diagnosis has the potential of saving millions of dollars to our healthcare system. But when patients do not have the resources to access prenatal care and prenatal diagnosis cost shifting occurs, escalating healthcare costs. Our current healthcare system promotes inequalities in its delivery. With the existing barriers to access, quality, and costs of prenatal diagnosis we are confronted with an inefficient and flawed system. PMID:21766544

Izquierdo, Luis A; Berkshire, Steven

2010-01-01

259

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

PubMed

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

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

2014-03-01

260

Genetic technologies and ethics.  

PubMed

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

Ardekani, Ali M

2009-01-01

261

Genetic Counseling for Mental Health Disorders  

Microsoft Academic Search

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

Elizabeth L. Pestka

2005-01-01

262

Pubic "Crab" Lice Diagnosis  

MedlinePLUS

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

263

Body Lice Diagnosis  

MedlinePLUS

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

264

Head Lice: Diagnosis  

MedlinePLUS

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

265

Lewy Body Dementia Diagnosis  

MedlinePLUS

... a clinical diagnosis. Currently, a conclusive diagnosis of LBD can be obtained only from a postmortem autopsy ... of the most controversial subjects in dealing with LBD. A medication that doesn't work for one ...

266

Preimplantation genetics: a case for prospective action.  

PubMed

Preimplantation genetics describes a newly-emerging field in medical genetics, the consequence of the implementation of clinical preimplantation diagnosis and the likely future development of germ-line gene therapy. Given the existing clinical and laboratory difficulties already demonstrated in preimplantation diagnosis and the sensitive ethical issues surrounding genetic manipulation of human embryos, there is a need for 1) critical and objective evaluation of developments in this field by human and medical geneticists and 2) development of guidelines for research and clinical practice in the years ahead. We propose a course of prospective action for preimplantation genetics implemented through the newly-formed American College of Medical Genetics in order to address the ethics, safety, accuracy, cost, and overall merit of preimplantation genetics. PMID:7802000

Pergament, E; Bonnicksen, A

1994-08-15

267

Risks of reproducing with a genetic disorder.  

PubMed

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

Byler, Melissa Ciano; Lebel, Robert Roger

2013-07-01

268

Genetics of man, 2nd ed  

SciTech Connect

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.

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

1986-01-01

269

Family Assessment and Genetic Counseling.  

ERIC Educational Resources Information Center

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

Carpenter, Pat; And Others

270

Diagnosis and management of hereditary hemochromatosis.  

PubMed

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

Salgia, Reena J; Brown, Kimberly

2015-02-01

271

Congenital metabolic diseases: Diagnosis and treatment  

SciTech Connect

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

Wapnir, R.A.

1985-01-01

272

New approaches to lymphoma diagnosis.  

PubMed

Recent years have brought an explosion of new diagnostic tools to the pathology of lymphomas, which have permitted more precise disease definition and recognition of factors that can predict prognosis and response to treatment. These new methods exploit both the biological features of normal lymphocytes as they progress through differentiation pathways and the genetic abnormalities that characterize malignant transformation. These features can be assessed in individual tumors with techniques that detect proteins (immunophenotyping), messenger RNA (in-situ hybridization), or changes in DNA [Southern blot, PCR, fluorescence in-situ hybridization (FISH), and gene sequencing]. Recently, the novel technology of "gene chips" or DNA microarrays has greatly enhanced the efficiency of analyzing expression of many genes simultaneously at the RNA level. Understanding the relationship of lymphoid neoplasms to their normal counterparts and the genetic events that lead to malignant transformation in lymphoid cells are essential for physicians caring for patients with lymphoma, since these are the basis of modern classification, diagnosis, and prognosis prediction. Although microarray technology is not ready for prime time in the daily diagnosis of lymphoma, practitioners should understand its potential and limitations. The vast majority of lymphoid neoplasms worldwide are derived from B lymphocytes at various stages of differentiation. The review by Harald Stein and colleagues present the events of normal B-cell differentiation that are relevant to understanding the biology of B-cell neoplasia. These include antigen receptor [immunoglobulin (Ig)] gene rearrangement, somatic mutations of the Ig variable region genes, receptor editing, Ig heavy chain class switch, and differential expression of a variety of adhesion molecules and receptor proteins as the cell progresses from a precursor B cell to a mature plasma cell. Most lymphoid neoplasms have genetic abnormalities, many of which appear to occur during the gene rearrangements and mutations that characterize normal B-cell differentiation. Dr. Riccardo Dalla Favera reviews the mechanisms of these translocations and other abnormalities, and their consequences for lymphocyte biology. The association of specific abnormalities with individual lymphomas is reviewed. Dr. Wing C. Chan reviews the technology and applications of DNA microarray analysis, its promises and pitfalls, and what it has already told us about the biology of lymphomas. Finally, what does this all mean? The applications, both current and future, of these discoveries to the diagnosis and treatment of patients with lymphoma are discussed by Dr. Nancy Lee Harris. PMID:11722985

Harris, N L; Stein, H; Coupland, S E; Hummel, M; Favera, R D; Pasqualucci, L; Chan, W C

2001-01-01

273

An Integrated Diagnosis Strategy for Congenital Myopathies  

PubMed Central

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

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

2013-01-01

274

Genetic Disorders  

MedlinePLUS

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

275

Genetic Screening  

NSDL National Science Digital Library

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

Irwin Slesnick

2004-01-01

276

Genetic programming  

Microsoft Academic Search

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

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

2000-01-01

277

Enterobiasis (Pinworm Infection): Diagnosis  

MedlinePLUS

... 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 For: Travelers ...

278

Prenatal diagnosis of familial type I choledochal cyst.  

PubMed

Familial choledochal cysts are extremely rare. High-resolution ultrasound now allows for the antenatal diagnosis of these anomalies. After delivery, elective surgical resection should be planned; however, increases in size, deterioration of liver function, and ascending cholangitis frequently force early intervention. We report an unusual occurrence of siblings with type I choledochal cysts and review the existing literature on cause, genetics, classification, diagnosis, and management of this disease. PMID:16452322

Clifton, Matthew S; Goldstein, Ruth B; Slavotinek, Anne; Norton, Mary E; Lee, Hanmin; Farrell, Jody; Nobuhara, Kerilyn K

2006-03-01

279

An Overview of Mutation Detection Methods in Genetic Disorders  

PubMed Central

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

Mahdieh, Nejat; Rabbani, Bahareh

2013-01-01

280

Late diagnosis of Lesch-Nyhan disease variant.  

PubMed

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

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

2013-01-01

281

Laboratory diagnosis of primary immunodeficiencies.  

PubMed

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

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

2014-04-01

282

Molecular diagnosis of chronic granulomatous disease  

PubMed Central

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

Roos, D; Boer, M

2014-01-01

283

Diagnosis of Growth Hormone Deficiency in Childhood  

PubMed Central

Purpose of Review The diagnosis of growth hormone deficiency (GHD) in childhood is challenging, in large part due to the lack of a true gold standard and the relatively poor performance of available diagnostic testing. This review discusses recent literature on this topic. Recent Findings Auxology and clinical judgment remain the foundation for the diagnosis of GHD. Provocative GH testing is poorly reproducible, dependent on factors such as body composition and pubertal status, and further limited by significant variability among commercially available GH assays. Measurement of IGF-I and IGFBP-3 is not diagnostically useful in isolation but is helpful in combination with other diagnostic measures. Neuroimaging is also useful to inform diagnosis, as pituitary abnormalities suggest a higher likelihood of GHD persisting into adulthood. Although genetic testing is not routinely performed in the diagnosis of GHD at the present time, multiple recent reports raise the possibility that it may play a more important role in diagnosing GHD in the future. Summary Beyond physicians’ integrated assessment of auxology, clinical presentation, and bone age, current tools to diagnose GHD are sub-optimal. Recent literature emphasizes the need to reappraise our current practice and to consider new tools for diagnosis. PMID:22157400

Stanley, Takara

2012-01-01

284

Genetic testing of inherited arrhythmias.  

PubMed

Syncope and risk of sudden death due to ventricular tachyarrhythmia are the common manifestations of several inherited disorders. Abnormalities of the genetic makeup may directly affect proteins controlling cardiac excitability in a structurally normal heart. Other diseases manifest primarily with ventricular arrhythmias even though the genetic mutations cause structural abnormalities of the myocardium. This is the case of arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy. Groundbreaking discoveries, starting from the 1990s until the beginning of the current decade, have provided fundamental knowledge on the major genes that confer an increased risk of arrhythmias and sudden death. Stems of such knowledge are the availability of genetic diagnosis, genotype-phenotype correlation, and genotype-based risk stratification schemes currently used in the clinical practice. This review provides a concise description of the known genes and key mechanisms involved in the pathogenesis of inherited arrhythmias. In addition, we outline possibilities, limitations, advantages, and potential threats of genetically screening for these genes. PMID:22427195

Napolitano, Carlo

2012-08-01

285

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

Microsoft Academic Search

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

Thomas J. Spencer; Joseph Biederman; Eric Mick

2007-01-01

286

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 & ...

287

Eugenic selection benefits embryos.  

PubMed

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

Walker, Mark

2014-06-01

288

Irritable bowel syndrome: Diagnosis and pathogenesis  

PubMed Central

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

El-Salhy, Magdy

2012-01-01

289

Vitiligo: Diagnosis, Treatment and Outcome  

MedlinePLUS

... Diseases and treatments U - W Vitiligo Diagnosis, treatment Vitiligo: Diagnosis, treatment, and outcome How do dermatologists diagnose vitiligo? If your dermatologist suspects that you have vitiligo, ...

290

Shingles: Diagnosis, Treatment, and Outcome  

MedlinePLUS

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

291

Diabetes Diagnosis Dilemma  

MedlinePLUS Videos and Cool Tools

... the lower right-hand corner of the player. Diabetes Diagnosis Dilemma HealthDay November 18, 2014 Related MedlinePlus Pages Diabetes Health Screening Transcript Approximately three out of every ...

292

Diagnosis of Osteoporosis.  

ERIC Educational Resources Information Center

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)

Wahner, H. W.

1987-01-01

293

Coping with a Diagnosis  

MedlinePLUS

... symptoms, medications, resources & more. Order Free Materials Today Parkinson's HelpLine Learn More Coping with a Diagnosis “The ... close to you has recently been diagnosed with Parkinson’s disease (PD), you are likely experiencing many emotions ...

294

Symptoms, Diagnosis & Treatment  

MedlinePLUS

... type "leukemia" or "lymphoma" in the search box) Non-Hodgkin's Lymphoma Symptoms Swollen, painless lymph nodes in the neck, ... A lymph node biopsy is used to diagnose non-Hodgkin's lymphoma. Sometimes the diagnosis may be delayed because enlarged ...

295

Dementia: Diagnosis and Tests  

MedlinePLUS

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

296

Pelvic Inflammatory Disease: Diagnosis  

MedlinePLUS

... JavaScript on. Read more information on enabling JavaScript. Pelvic Inflammatory Disease Skip Content Marketing Share this: Main Content Area Diagnosis PID can be difficult for your healthcare provider to ...

297

[Differential diagnosis of epilepsy].  

PubMed

Epilepsy may cause convulsion or transient loss of consciousness. Differential diagnosis of convulsion includes acute symptomatic seizure, psychogenic nonepileptic seizure, and epilepsy. Long duration of seizure, fluctuating course, and asynchronous movements favor psychogenic nonepileptic seizures. Occurrence of seizure from EEG-confirmed sleep, postictal confusion, and stertorous breathing favor epileptic seizures. Differential diagnosis of transient loss of consciousness includes syncope, epilepsy, and hypoglycemia. Causes of syncope include vasovagal syncope, arrhythmia, and orthostatic hypotension. PMID:24912284

Oishi, Minoru

2014-05-01

298

Diagnosis of urticaria.  

PubMed

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

Schoepke, Nicole; Doumoulakis, Georgios; Maurer, Marcus

2013-05-01

299

Diagnosis of Human Giardiasis  

Microsoft Academic Search

\\u000a Although progress has been made in the non-morphological diagnosis of Giardiasis, examination (usually of feces) by microscopy\\u000a remains the cornerstone in the diagnosis of intestinal parasitic infections. Routine examination of stool specimens is the\\u000a best known and most frequently performed laboratory procedure worldwide in which almost all intestinal parasites can be detected\\u000a at the same time. In Europe, standard methods

Huw V. Smith; Theo G. Mank

300

Applying Wavelet Support Vector Machine to Analog Circuit Fault Diagnosis  

Microsoft Academic Search

Based on vector wavelet kernel function, a method for analog circuit diagnosis based on genetic algorithm (GA) and least squares wavelet support vector machine (LSWSVM) is proposed. Using wavelet package as a tool for extracting feature, the GA-LSWSVM is then applied to the filet circuit after training by GA; the simulation results have shown that the method can enhances the

Zuo Lei; Hou Ligang; Zhang Wang; Wu Wuchen

2010-01-01

301

Insights Into the Diagnosis and Treatment of Lysosomal Storage Diseases  

Microsoft Academic Search

ysosomal storage diseases (LSDs) are a group of genetic disorders that result from de- fective lysosomal metabolism or export of naturally occurring compounds. Signs and symptoms are variable both within and between disorders depending on the location and extent of storage. Many patients develop neurologic symptoms that become obvi- ous from the newborn period to adulthood. Diagnosis of suspected patients

David A. Wenger; Stephanie Coppola; Shu-Ling Liu

2003-01-01

302

BIOINFORMATICS ANALYSIS OF OMICS DATA TOWARDS CANCER DIAGNOSIS AND PROGNOSIS  

E-print Network

Cancer Predicts Patient Survival 42 CHAPTER 4. Molecular Classification of Cancer Using Genetic transformation 18 2.1 A typical workflow of molecular cancer classification and prediction model 38 3BIOINFORMATICS ANALYSIS OF OMICS DATA TOWARDS CANCER DIAGNOSIS AND PROGNOSIS by Jianjun Yu

Fernandez, Thomas

303

Diagnosis of muscle diseases presenting with early respiratory failure.  

PubMed

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

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

2014-11-01

304

Genetic Counseling.  

ERIC Educational Resources Information Center

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

Exceptional Parent, 1987

1987-01-01

305

Genetic Engineering  

ERIC Educational Resources Information Center

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

Phillips, John

1973-01-01

306

Condition Diagnosis for Rotating Machinery Using Support Vector Machines and Symptom Parameters in Frequency Domain  

Microsoft Academic Search

Up to now, many condition diagnosis methods based on the traditional artificial intelligence, such as neural networks (NN), genetic algorithms (GA), etc., have been proposed in the field of condition diagnosis for rotating machinery. These methods depend on the assumption that the number of samples tends to infinity, and also require a large amount of training samples and highly sensitive

Hongtao Xue; Peng Chen

2011-01-01

307

The Emerging Genetics of Primary Ciliary Dyskinesia  

PubMed Central

Primary ciliary dyskinesia (PCD) is an autosomal recessive, rare, genetically heterogeneous condition characterized by oto-sino-pulmonary disease together with situs abnormalities (Kartagener syndrome) owing to abnormal ciliary structure and function. Most patients are currently diagnosed with PCD based on the presence of defective ciliary ultrastructure. However, diagnosis often remains challenging due to variability in the clinical phenotype and ciliary ultrastructural changes. Some patients with PCD have normal ciliary ultrastructure, which further confounds the diagnosis. A genetic test for PCD exists but is of limited value because it investigates only a limited number of mutations in only two genes. The genetics of PCD is complicated owing to the complexity of axonemal structure that is highly conserved through evolution, which is comprised of multiple proteins. Identifying a PCD-causing gene is challenging due to locus and allelic heterogeneity. Despite genetic heterogeneity, multiple tools have been used, and there are 11 known PCD-causing genes. All of these genes combined explain approximately 50% of PCD cases; hence, more genes need to be identified. This review briefly describes the current knowledge regarding the genetics of PCD and focuses on the methodologies used to identify novel PCD-causing genes, including a candidate gene approach using model organisms, next-generation massively parallel sequencing techniques, and the use of genetically isolated populations. In conclusion, we demonstrate the multipronged approach that is necessary to circumvent challenges due to genetic heterogeneity to uncover genetic causes of PCD. PMID:21926394

Omran, Heymut; Ferkol, Thomas W.

2011-01-01

308

Fibromyalgia Syndrome: Etiology, Pathogenesis, Diagnosis, and Treatment  

PubMed Central

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

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

2012-01-01

309

Diagnosis and management of primary ciliary dyskinesia  

PubMed Central

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

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

2014-01-01

310

Image processing for medical diagnosis using CNN  

NASA Astrophysics Data System (ADS)

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

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

2003-01-01

311

Psoriatic arthritis: Epidemiology, diagnosis, and treatment  

PubMed Central

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

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

2014-01-01

312

Genetic and epigenetic alterations in differentiated thyroid carcinoma  

PubMed Central

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

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

2013-01-01

313

Genetic and epigenetic alterations in differentiated thyroid carcinoma.  

PubMed

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

Brehar, A C; Brehar, F M; Bulgar, A C; Dumitrache, C

2013-01-01

314

Noninvasive prenatal diagnosis using next-generation sequencing.  

PubMed

Nowadays, prenatal diagnosis is necessary for pregnant women. For the parents who are expecting a child, the genetic test may provide the information whether they are carrying rare gene mutations and whether they are at risk of passing them onto their offspring. However, the ultimate determination of genetic diseases often requires invasive procedures such as amniocentesis and chorionic villus sampling, which may cause fetal miscarriage. A noninvasive type of prenatal diagnosis needs to be developed in clinical practice to dispel safety concerns. In this paper, we will review the technical advancement of using maternal circulating nucleic acids as the sample in noninvasive studies, and highlight the utilization of next-generation sequencing in the screening of genetic diseases. PMID:24192219

Xu, Liang; Shi, Rui

2014-01-01

315

Software Fault Diagnosis Peter Zoeteweij  

E-print Network

Software Fault Diagnosis Peter Zoeteweij , Rui Abreu, and Arjan J.C. van Gemund Embedded Software systems. This tutorial paper aims to give an overview of automated diagnosis applied to software faults existing diagnosis / debugging systems that apply SFL, and other approaches to software fault diagnosis. We

Zoeteweij, Peter

316

Prenatal diagnosis of the Meckel syndrome.  

PubMed

Prenatal diagnosis of the Meckel syndrome was made at 20 weeks of gestation from the findings of a biparietal diameter smaller than expected for gestational age, a grossly raised amniotic fluid alphafetoprotein level and a rapid growth of foetal macrophages after 20 hours culture. Termination at 23 weeks of gestation resulted in a male foetus with an occipital encephalocele, microcephaly, polydactyly, and bilateral polycystic kidneys. This case report emphasies the importance for genetic counselling of delineating the Meckel syndrome from the multifactorial cases of neural tube defects, and also illustrates, at least in some cases, that the syndrome can be diagnosed in utero. PMID:83212

Nevin, N C; Thompson, W; Davison, G; Horner, W T

1979-01-01

317

Fetal cystic hygroma: prenatal diagnosis and management.  

PubMed

Seventeen cases of fetal cystic hygroma detected during ultrasound examination are reported. In nine instances, associated abnormalities were recognized, such as fetal hydrops and a two-vessel cord. All diagnoses were confirmed at autopsy. Karyotyping revealed normal findings in six cases, Turner's syndrome in eight cases, and Edwards' syndrome in one case; culture failure occurred in the remaining two cases. An ultrasound diagnosis of cystic hygroma should be followed by a careful search for other anomalies and by fetal karyotyping. Afterward, genetic counseling is indicated. PMID:3292980

Pijpers, L; Reuss, A; Stewart, P A; Wladimiroff, J W; Sachs, E S

1988-08-01

318

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

E-print Network

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

Harman, Neal.A.

319

Diagnosis of Charcot-Marie-Tooth Disease  

PubMed Central

Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy (HMSN) is a genetically heterogeneous group of conditions that affect the peripheral nervous system. The disease is characterized by degeneration or abnormal development of peripheral nerves and exhibits a range of patterns of genetic transmission. In the majority of cases, CMT first appears in infancy, and its manifestations include clumsiness of gait, predominantly distal muscular atrophy of the limbs, and deformity of the feet in the form of foot drop. It can be classified according to the pattern of transmission (autosomal dominant, autosomal recessive, or X linked), according to electrophysiological findings (demyelinating or axonal), or according to the causative mutant gene. The classification of CMT is complex and undergoes constant revision as new genes and mutations are discovered. In this paper, we review the most efficient diagnostic algorithms for the molecular diagnosis of CMT, which are based on clinical and electrophysiological data. PMID:19826499

Banchs, Isabel; Casasnovas, Carlos; Albertí, Antonia; De Jorge, Laura; Povedano, Mónica; Montero, Jordi; Martínez-Matos, Juan Antonio; Volpini, Victor

2009-01-01

320

Prenatal diagnosis and the trouble with eugenics.  

PubMed

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

Landeweerd, Laurens

2009-01-01

321

The '-osis' Diagnosis  

MedlinePLUS

... from "endometrium" (meaning inner lining of the uterus) Hemochromatosis – This is a genetic disease in which there ... field instantly recognize the speaker's intent. The term "hemochromatosis," for example, means something more accurate or precise ...

322

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

E-print Network

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

Paris-Sud XI, Université de

323

Immunological diagnosis of Werner syndrome by down-regulated and truncated gene products  

Microsoft Academic Search

Although immunological methods are widely used to diagnose various infectious diseases, they have rarely been employed to detect genetic diseases. In this study, we have established an immunoblot analysis system for the diagnosis of Werner syndrome (WS), a recessive genetic disorder causing premature aging and an enhanced risk of rare cancers. The method uses an immunoblot technique with specific monoclonal

Makoto Goto; Yukako Yamabe; Miwa Shiratori; Masako Okada; Tamae Kawabe; Takehisa Matsumoto; Masanobu Sugimoto; Yasuhiro Furuichi

1999-01-01

324

Fetal megacystis: differential diagnosis.  

PubMed

The purpose of our retrospective observational series was to determine whether the sonographic characteristics of fetal megacystic bladders can be used to reliably establish the most likely diagnosis in fetuses with this condition. The sonographic records of pregnant patients referred to our institutions over a 10-year period who were found on initial 2-dimensional sonography to be carrying fetuses with megacystis were examined for evidence of a keyhole sign, bladder thickness, amniotic fluid index, and fetal sex. When available, 3-/4-dimensional sonography, Doppler angiography, tomographic ultrasound imaging, virtual organ computer-aided analysis, and automatic volume calculation were used as part of the detailed fetal anatomic survey. Twenty fetuses with megacystis were identified. Seventeen were male; 2 were female; and 1 had ambiguous genitalia. All male fetuses with megacystis originally had a diagnosis of prune belly syndrome. The diagnosis for 10 male fetuses with a keyhole sign was changed to megacystis secondary to posterior urethral valves. The fetus with ambiguous genitalia had prune belly syndrome. One of the female fetuses had a diagnosis of urethral atresia, and the diagnosis for the other female fetus was megacystis-microcolon-intestinal hypoperistalsis syndrome. In conclusion, in fetuses with megacystic bladders, it is possible to distinguish between cases with prune belly syndrome, posterior urethral valves, urethral atresia, and megacystis-microcolon-intestinal hypoperistalsis syndrome by a detailed anatomic survey using 2- and 3-/4-dimensioinal sonographic techniques. PMID:21632999

Osborne, Newton G; Bonilla-Musoles, Fernando; Machado, Luiz Eduardo; Raga, Francisco; Bonilla, Francisco; Ruiz, Fernando; Pérez Guardia, Carla M; Ahluwalia, Balwant

2011-06-01

325

Genetic causes of male infertility.  

PubMed

Male infertility, affecting around half of the couples with a problem to get pregnant, is a very heterogeneous condition. Part of patients are having a defect in spermatogenesis of which the underlying causes (including genetic ones) remain largely unknown. The only genetic tests routinely used in the diagnosis of male infertility are the analyses for the presence of Yq microdeletions and/or chromosomal abnormalities. Various other single gene or polygenic defects have been proposed to be involved in male fertility. Yet, their causative effect often remains to be proven. The recent evolution in the development of whole genome-based techniques may help in clarifying the role of genes and other genetic factors involved in spermatogenesis and spermatogenesis defects. PMID:24768008

Stouffs, Katrien; Seneca, Sara; Lissens, Willy

2014-05-01

326

Cancer Genetics Professionals  

Cancer.gov

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

327

What is Genetic Counseling?  

MedlinePLUS

... 1983) For information on genetic counselors and genetic counseling training programs, please download this helpful brochure from the Association of Genetic Counseling Program Directors: Who are Genetic Counselors? Practicing genetic ...

328

Genetics Home Reference: CHMP2B-related frontotemporal dementia  

MedlinePLUS

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

329

Diagnosis of hepatocellular carcinoma  

PubMed Central

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

Di Bisceglie, Adrian M.

2005-01-01

330

Remote diagnosis server  

NASA Technical Reports Server (NTRS)

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

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

2004-01-01

331

[Imaging diagnosis of dementia].  

PubMed

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

Ishii, Kenji

2014-04-01

332

Human prenatal diagnosis  

SciTech Connect

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.

Filkins, K.; Russo, R.J.

1985-01-01

333

Diagnosis of mitochondrial myopathies.  

PubMed

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

Milone, Margherita; Wong, Lee-Jun

2013-01-01

334

Genetic Disorders  

MedlinePLUS

... extra chromosome. A common trisomy is trisomy 21 (Down syndrome) . Other trisomies include trisomy 13 (Patau syndrome) and ... within the first year of life. Trisomy 21 (Down Syndrome): A genetic disorder in which abnormal features of ...

335

Genetic Disorders  

MedlinePLUS

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

336

Arthropod Genetics.  

ERIC Educational Resources Information Center

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

Zumwalde, Sharon

2000-01-01

337

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

338

Genetic Alliance  

MedlinePLUS

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

339

Genetics and celiac disease: the importance of screening.  

PubMed

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

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

2015-02-01

340

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

PubMed

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

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

2004-01-01

341

Population Genetics  

Microsoft Academic Search

\\u000a \\u000a Population genetics is the study of evolutionary genetics at the population level focusing on the exchange of alleles and genes within and between\\u000a populations as well as the forces that cause or maintain these exchanges. This exchange of genes and alleles causes changes\\u000a in the specific allele and hence genotype frequencies within and between populations. Studying this evolution helps us

Jill S. Barnholtz-Sloan; Hemant K. Tiwari

342

Ciona Genetics  

PubMed Central

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

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

2010-01-01

343

NEW DEVELOPMENTS IN THE DIAGNOSIS AND TREATMENT OF THYROID CANCER  

PubMed Central

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

Schneider, David F.; Chen, Herbert

2013-01-01

344

Conservation Genetics at the Species Boundary  

Microsoft Academic Search

Conservation genetics has expanded its purview such that molecular techniques are now used rou- tinely to prioritize populations for listing and protection and infer their historical relationships in addition to addressing more traditional questions of heterozygosity and inbreeding depression. Failure to specify whether molecular data are being used for diagnosis-related questions or for population viability questions, however, can lead either

Paul Z. Goldstein; Robert Desalle; George Amato; Alfried P. Vogler

2000-01-01

345

Avoiding Pitfalls in Molecular Genetic Testing  

PubMed Central

The molecular testing options available for the diagnosis of genetic disorders are numerous and include a variety of different assay platforms. The consultative input of molecular pathologists and cytogeneticists, working closely with the ordering clinicians, is often important for definitive diagnosis. Herein, we describe two patients who had long histories of unexplained signs and symptoms with a high clinical suspicion of an underlying genetic etiology. Initial molecular testing in both cases was negative, but the application of high-resolution array comparative genomic hybridization technology lead to definitive diagnosis in both cases. We summarize the clinical findings and molecular testing in each case, discuss the differential diagnoses, and review the clinical and pathological findings of Mowat-Wilson syndrome. This report highlights the importance for those involved in molecular testing to know the nature of the underlying genetic abnormalities associated with the suspected diagnosis, to recognize the limitations of each testing platform, and to persistently pursue repeat testing using high-resolution technologies when indicated. This concept is applicable to both germline and somatic molecular genetic testing. PMID:21497296

Kluk, Michael Joseph; An, Yu; James, Philip; Coulter, David; Harris, David; Wu, Bai-Lin; Shen, Yiping

2011-01-01

346

Invasive prenatal genetic testing: A Catholic healthcare provider's perspective.  

PubMed

Invasive prenatal testing is performed for a variety of reasons, but the most common indication is for genetic testing of the fetus. Although many times the information obtained from this type of testing results in selective termination of fetuses with genetic diagnoses, the information itself may be morally neutral. Should a Catholic healthcare provider be willing to perform invasive prenatal testing in the setting of uncertainty with respect to the patient's plans following a diagnosis of a genetic abnormality? PMID:25473130

Bringman, Jay J

2014-11-01

347

Assessment, Diagnosis, and Treatment.  

ERIC Educational Resources Information Center

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

Mullis, Thomas

348

Dry eye diagnosis  

Microsoft Academic Search

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.

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

2008-01-01

349

Sonographic diagnosis of pneumothorax  

PubMed Central

Lung sonography has rapidly emerged as a reliable technique in the evaluation of various thoracic diseases. One important, well-established application is the diagnosis of a pneumothorax. Prompt and accurate diagnosis of a pneumothorax in the management of a critical patient can prevent the progression into a life-threatening situation. Sonographic signs, including ‘lung sliding’, ‘B-lines’ or ‘comet tail artifacts’, ‘A-lines’, and ‘the lung point sign’ can help in the diagnosis of a pneumothorax. Ultrasound has a higher sensitivity than the traditional upright anteroposterior chest radiography (CXR) for the detection of a pneumothorax. Small occult pneumothoraces may be missed on CXR during a busy trauma scenario, and CXR may not always be feasible in critically ill patients. Computed tomography, the gold standard for the detection of pneumothorax, requires patients to be transported out of the clinical area, compromising their hemodynamic stability and delaying the diagnosis. As ultrasound machines have become more portable and easier to use, lung sonography now allows a rapid evaluation of an unstable patient, at the bedside. These advantages combined with the low cost and ease of use, have allowed thoracic sonography to become a useful modality in many clinical settings. PMID:22416161

Husain, Lubna F; Hagopian, Laura; Wayman, Derek; Baker, William E; Carmody, Kristin A

2012-01-01

350

[Diagnosis of congenital infection].  

PubMed

In general, congenital diagnosis is based on: a) maternal serologic assays; b) microbiologic study of amniotic fluid or fetal blood sampling; and c) serology in children and microorganism detection by polymerase chain reaction (PCR) or culture. Congenital infections due to cytomegalovirus, herpes simplex, varicella, B19 erythrovirus and toxoplasmosis are usually the result of primary infection in the mother. Therefore, when IgG antibodies are detected before pregnancy, these infections are ruled out. Definitive serologic diagnosis of acute infection in pregnant women requires the demonstration of seroconversion (i.e., from seronegative to seropositive). In these cases, amniotic fluid or fetal blood sampling should be performed to determine the presence of intrauterine congenital infection. Cytomegalovirus, rubella and toxoplasmosis can be diagnosed by detection of specific IgM antibodies in fetal blood. However, PCR in amniotic fluid has replaced conventional prenatal diagnostic techniques, including fetal blood sampling, in the diagnosis of these infections. In the newborn, these infections may be confirmed by measuring IgM specific antibodies. B19 erythrovirus can be detected by PCR in amniotic fluid or fetal blood. Congenital varicella-zoster infection may be diagnosed on the basis of persistence of IgG antibodies after birth. Definitive diagnosis of herpes simplex virus infection requires viral isolation. Swabs or scraping from clinical specimens can be inoculated into susceptible cell lines for isolation. PMID:22305665

Sampedro Martínez, Antonio; Martínez, Luis Aliaga; Teatino, Pablo Mazuelas; Rodríguez-Granger, Javier

2011-12-01

351

Multi-Disciplinary Diagnosis.  

ERIC Educational Resources Information Center

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

Schiffman, Gilbert B.

352

About Alzheimer's Disease: Diagnosis  

MedlinePLUS

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

353

Genetic screening  

PubMed Central

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

Andermann, Anne; Blancquaert, Ingeborg

2010-01-01

354

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

ERIC Educational Resources Information Center

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…

Kaut, Kevin P.

2006-01-01

355

Huntington's disease: pathogenesis, diagnosis and treatment.  

PubMed Central

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

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

1994-01-01

356

Biomarkers, genetics and cancer  

SciTech Connect

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

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

1985-01-01

357

Neural tube defects--prenatal diagnosis and management.  

PubMed Central

Neural tube defects rank second to congenital heart disease as a major cause of congenital malformation. Recent developments in ultrasound have improved prenatal diagnosis. Due to anomaly scans at 18 weeks gestation and the availability of a genetic clinic, prenatal diagnosis of neural tube defects at the Royal Maternity Hospital was 91.2% during 1987-1989. However, only 50% of parents accept termination of pregnancy and it is questionable if prenatal diagnosis is of benefit to those who wish to continue with the pregnancy. Parents may accept the situation better at birth, having had time to come to terms with it, helped with support from the obstetrician, clinical geneticist, paediatrician, genetic nurse and social worker. For some affected fetuses who have better muscle function and leg movement at term it appears from the literature that the outcome may be improved by caesarean section delivery. In Ireland fetuses with neural tube defects will continue to be delivered, as termination is unacceptable to many, but despite this there may be a positive benefit from prenatal diagnosis of neural tube defects. Prospective randomised controlled trials are needed to confirm benefit from delivery by caesarean section for fetuses with a good prognosis. As a result of prenatal diagnosis of a neural tube lesion the fetus should enjoy benefit in terms of physical morbidity, and the parents should benefit in terms of psychological morbidity. PMID:1481301

Hamilton, R. A.; Dornan, J. C.

1992-01-01

358

Scabies: Diagnosis, Treatment, and Outcome  

MedlinePLUS

... treatments Q - T Scabies Diagnosis, treatment Scabies: Diagnosis, treatment, and outcome How do dermatologists diagnose scabies? A ... only available with a doctor’s prescription. Who needs treatment? The person diagnosed with scabies and everyone who ...

359

Prenatal diagnosis and management of fetal cardiovascular malformations.  

PubMed

Screening for fetal cardiovascular malformations is widely performed. Its accuracy is not yet satisfactory, but better training of ultrasonographers and extension from the four-chamber view to the study of the outflow tract are probably clues to an improvement. The main impact of prenatal diagnosis is still the termination of pregnancy for severe malformations and for those associated with chromosomal or extracardiac anomalies. There is now evidence that prenatal diagnosis improves perinatal morbidity or mortality for some malformations. New information about the molecular genetic basis of congenital heart disease will help in management and counselling. PMID:10813571

Todros, T

2000-04-01

360

Genetic Engineering  

NSDL National Science Digital Library

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

Morrissette-Johnson, Winona

361

Biology 2250 Principles of Genetics  

E-print Network

of Human Genetics Human Genetics Journal of Heredity CurrentGenetics Molecular Biology and Evolution Animal Genetics Human Molecular Genetics Genetics European J. of Human Genetics Genetics Selection Evolution American J. Human Genetics Heredity Annals of Human Genetics Hereditas Opthalmic Genetics Japanese Journal

Innes, David J.

362

Biology 2250 Principles of Genetics  

E-print Network

of Human Genetics Human Genetics Journal of Heredity Current Genetics Molecular Biology and Evolution Genetics Human Molecular Genetics Genetics European J. of Human Genetics Genetics Selection Evolution American J. Human Genetics Heredity Annals of Human Genetics Hereditas Opthalmic Genetics Japanese Journal

Innes, David J.

363

Diagnosis of Seizure Disorders  

PubMed Central

The author addresses the diagnosis of seizure disorders by discussing clinical features of the different types of seizures, including generalized tonic-clonic, absence, myoclonic, partial complex seizures, and non-epileptic or “pseudoseizures.” She also discusses the use of appropriate laboratory tests, electroencephalography, computed tomography, magnetic resonance imaging, and positron emission tomographic scanning. The rationale of and approach to treatment of these conditions with some of the common anticonvulsant drugs (phenytoin, carbamazepine, valproic acid, phenobarbital, and primidone) is provided. PMID:21234044

Purves, Sherrill J.

1990-01-01

364

Prevention, Diagnosis and Services  

Microsoft Academic Search

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

Eva Bermejo; María Luisa Martínez-Frías

365

Diagnosis of thymoma  

PubMed Central

The diagnosis of thymic epithelial neoplasm has been a topic of controversy for many years. Reasons for this include the lack of predictive value associated with the morphology of these tumours and the multiplicity of classification schemes and terminologies proposed over the years. Recently, a new classification schema was introduced by the World Health Organization (WHO) in an attempt to standardise nomenclature and facilitate the diagnosis of primary thymic epithelial neoplasms. This schema, although not originally intended as a new histological classification, but rather as a means for translating equivalent terms from the various existing classifications, has represented a major step forward in this direction. However, problems still exist with the WHO schema, particularly with some of the criteria for the various histological subtypes as well as with issues of interobserver reproducibility. For this reason, we favour using a much more simplified approach to the morphological classification of thymic epithelial neoplasms. A personal approach to the morphological diagnosis of thymoma is described, with a brief explanation for the rationale for simplifying the existing diagnostic categories. PMID:16679354

Suster, S

2006-01-01

366

Culture and psychiatric diagnosis.  

PubMed

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

Lewis-Fernández, Roberto; Aggarwal, Neil Krishan

2013-01-01

367

Vaginitis: diagnosis and management.  

PubMed

Vaginitis is one of the most common ambulatory problems to occur in women. It is a disorder responsible for > 10% of visits made to providers of women's health care. Although vaginal infections are the most common cause, other considerations include cervicitis, a normal vaginal discharge, foreign-body vaginitis, contact vaginitis, atrophic vaginitis, and desquamative inflammatory vaginitis. The medical history and examination are an important source of clues to the underlying diagnosis. However, making a definitive diagnosis requires skillful performance of office laboratory procedures, including the vaginal pool wet mount examination, determination of the vaginal pH, and the whiff test. Vaginal and cervical cultures, nucleic acid tests, and point-of-care tests are available and may be required in selected patients. Once a specific diagnosis is made, effective therapy can be prescribed. Candida vaginitis is generally treated with either the vaginal administration of an imidazole or triazole antifungal agent or the prescription of oral fluconazole. Oral nitroimidazole agents, metronidazole or tinidazole, are the only effective treatments for trichomoniasis in the United States. Bacterial vaginosis, which has been linked to important gynecologic and pregnancy complications, can be treated with an available oral or topical agent containing either a nitroimidazole or clindamycin. PMID:21084788

Quan, Martin

2010-11-01

368

Human Genetics: Careers in Human Genetics  

MedlinePLUS

Careers in Human Genetics What is genetics? Genetics is the study of genes, their functions, and their effects. Why become a ... demand for geneticists? As the details of the human genome unfold, the variety of opportunities for people ...

369

Genetics of SCID  

PubMed Central

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

2010-01-01

370

[Larsen-syndrome: final diagnosis following multiple surgical interventions].  

PubMed

Larsen-syndrome is a rare genetic skeletal dysplasia belonging to the group of actin-binding filamin B associated diseases. The features include congenital dislocations of the large joints, scoliosis and cervical kyphosis, short, broad, spatulate distal phalanges, and distinctive craniofacies. Diagnosis is based on clinical and radiographic findings and confirmed by molecular genetic testing. The authors have performed filamin B molecular genetic analysis since 2005 and have found several cases with unusual phenotypes since. This case report presents the diagnostic difficulties of a 30-year-old woman, who was operated several times with congenital hip dislocations and foot deformities. The craniofacial features, short, broad, spatulate fingers, scoliosis and cervical kyphosis directed diagnosis towards Larsen-syndrome and molecular genetic analysis confirmed a previously-described heterozygous missense mutation (c.G679A). They conclude that genetic analysis performed in time would prevent additional superfluous long diagnostic procedures in patients with rare diseases and would ensure adequate supportive therapy and management of the symptoms. PMID:23335724

Kisfali, Péter; Komlósi, Katalin; Hadzsiev, Kinga; Melegh, Béla

2013-01-27

371

Agenesis of the corpus callosum: a clinical approach to diagnosis.  

PubMed

This review article aims to guide the clinician in establishing a diagnosis in patients with agenesis of the corpus callosum (ACC), presenting antenatally or postnatally. ACC may be isolated, or occur in association with other neuroanatomical lesions and/or congenital anomalies, and has many different genetic causes. Neuropsychological outcome varies considerably from normal to profound intellectual disability depending on the etiology. Approximately 25% of individuals with antenatally diagnosed apparently isolated ACC have intellectual disability. Subtle neurological, social, and learning deficits may still occur in those with normal intelligence and longitudinal neurocognitive follow-up is recommended for all children with ACC. The finding of ACC should prompt detailed clinical assessment in order to determine and manage the underlying condition. It is recognized that genetic factors contribute to ACC in the vast majority of cases. Less commonly ACC can result from antenatal infections, vascular or toxic insults, and it is increasingly recognized that ACC, particularly isolated ACC, may be due to an interaction of a number of "modifier" genetic and environmental factors. There are a large number of genetic conditions in which ACC may be a feature. We suggest a diagnostic algorithm to help guide the clinician towards diagnosis, to provide outcome advice and to aid in genetic counseling. PMID:24866859

Palmer, Elizabeth Emma; Mowat, David

2014-06-01

372

Recent advances in primary ciliary dyskinesia genetics  

PubMed Central

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

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

2015-01-01

373

Genetic Drift  

NSDL National Science Digital Library

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

Scott Cooper

374

Cutaneous porphyrias part I: epidemiology, pathogenesis, presentation, diagnosis, and histopathology.  

PubMed

The porphyrias are a group of disorders characterized by defects in the heme biosynthesis pathway. Many present with skin findings including photosensitivity, bullae, hypertrichosis, and scarring. Systemic symptoms may include abdominal pain, neuropsychiatric changes, anemia, and liver disease. With advances in DNA analysis, researchers are discovering the underlying genetic causes of the porphyrias, enabling family members to be tested for genetic mutations. Here we present a comprehensive review of porphyria focusing on those with cutaneous manifestations. In Part I, we have included the epidemiology, pathogenesis, presentation, diagnosis, and histopathology. Treatment and management options will be discussed in Part II. PMID:24261722

Horner, Mary E; Alikhan, Ali; Tintle, Suzanne; Tortorelli, Silvia; Davis, Dawn Marie R; Hand, Jennifer L

2013-12-01

375

Genetic Counseling Program Information  

E-print Network

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

Berdichevsky, Victor

376

Five cases of paroxysmal kinesigenic dyskinesia by genetic diagnosis  

PubMed Central

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

CHEN, GUO-HONG

2015-01-01

377

Genetic diagnosis strategy of hereditary non-polyposis colorectal cancer  

Microsoft Academic Search

AIM: To study the characteristics of mismatch repair gene mutation of Chinese hereditary non-polyposis colorectal cancer (HNPCC) and hMLH1 gene promoter methylation, and to improve the screening strategy and explore the pertinent test methods. METHODS: A systematic analysis of 30 probands from HNPCC families in the north of China was performed by immunohistochemistry, microsatellite instability (MSI), gene mutation and methylation

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

2009-01-01

378

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

PubMed

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

Blau, Nenad; Shen, Nan; Carducci, Carla

2014-07-01

379

Towards applications of synthetic genetic polymers in diagnosis and therapy.  

PubMed

Aptamers are a class of single-stranded nucleic acid ligands that can bind their targets with high specificity and affinities rivalling those of antibodies. First described over 20 years ago by Tuerk & Gold [1] and Ellington & Szostak [2] (who coined the name), their promise as both diagnostic and therapeutic agents remains to be realised. Key problems include the generally low biostability of the standard DNA/RNA or mixed RNA/2'F-DNA backbones under physiological conditions, limited chemical diversity of functional groups on the natural nucleobases, and the difficulty in reliably discovering aptamer ligands to some therapeutic targets. This review will describe recent progress in developing aptamer selection technology as well as expanding aptamer chemistry and informational complexity to improve aptamer discovery and properties. PMID:25285754

Taylor, Alexander I; Arangundy-Franklin, Sebastian; Holliger, Philipp

2014-10-01

380

Diagnosis of ADHD and its Behavioral, Neurologic and Genetic Roots  

PubMed Central

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

Mueller, Kathryn L.; Tomblin, J. Bruce

2014-01-01

381

Genetic Profiling for Risk Reduction in Human Cardiovascular Disease  

PubMed Central

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

Puckelwartz, Megan J.; McNally, Elizabeth M.

2014-01-01

382

Striving for Harmonisation and Living Without it  

Microsoft Academic Search

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

Minou Friele

383

A genetic algorithm tutorial  

Microsoft Academic Search

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...

DARRELL WHITLEY

1993-01-01

384

An Update on Laboratory Diagnosis of Liver Inherited Diseases  

PubMed Central

Liver inherited diseases are a group of genetically determined clinical entities that appear with an early chronic liver involvement. They include Wilson's disease (hepatolenticular degeneration), hereditary hemochromatosis, and alpha-1-antitrypsin deficiency. In addition, cystic fibrosis, although it is not specifically a liver disease, may cause a severe liver involvement in a significant percentage of cases. For all these pathologies, the disease gene is known, and molecular analysis may contribute to the unequivocal diagnosis. This approach could avoid the patient invasive procedures and limit complications associated with a delay in diagnosis. We review liver inherited diseases on the basis of the genetic defect, focusing on the contribution of molecular analysis in the multistep diagnostic workup. PMID:24222913

Elce, Ausilia; Amato, Felice

2013-01-01

385

An update on laboratory diagnosis of liver inherited diseases.  

PubMed

Liver inherited diseases are a group of genetically determined clinical entities that appear with an early chronic liver involvement. They include Wilson's disease (hepatolenticular degeneration), hereditary hemochromatosis, and alpha-1-antitrypsin deficiency. In addition, cystic fibrosis, although it is not specifically a liver disease, may cause a severe liver involvement in a significant percentage of cases. For all these pathologies, the disease gene is known, and molecular analysis may contribute to the unequivocal diagnosis. This approach could avoid the patient invasive procedures and limit complications associated with a delay in diagnosis. We review liver inherited diseases on the basis of the genetic defect, focusing on the contribution of molecular analysis in the multistep diagnostic workup. PMID:24222913

Zarrilli, Federica; Elce, Ausilia; Scorza, Manuela; Giordano, Sonia; Amato, Felice; Castaldo, Giuseppe

2013-01-01

386

Rabies: Diagnosis in Animals and Humans  

MedlinePLUS

... gov . Rabies Share Compartir Diagnosis in animals and humans Diagnosis in animals A diagnosis of rabies can ... based on current public health recommendations. Diagnosis in humans Several tests are necessary to diagnose rabies ante- ...

387

Determining the Pathogenicity of Genetic Variants Associated with Cardiac Channelopathies  

PubMed Central

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

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

2015-01-01

388

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

PubMed

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

2015-01-01

389

Inherited thrombocytopenias: an approach to diagnosis and management.  

PubMed

Inherited thrombocytopenias vary in their presentation, associated features, and molecular etiologies. An accurate diagnosis is important to provide appropriate therapy as well as counseling for the individual and their family members. As the genetic basis of more disorders is understood, it will be possible to diagnose a greater fraction of patients as well as learn more about the process of megakaryopoiesis and platelet production. PMID:22846067

Geddis, A E

2013-02-01

390

Genetically and medically susceptible workers.  

PubMed

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

Mohr, S; Gochfeld, M; Pransky, G

1999-01-01

391

Case for diagnosis.  

PubMed

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

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

2014-01-01

392

Diagnosis of leishmaniasis.  

PubMed

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

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

2014-08-01

393

Case for diagnosis*  

PubMed Central

Dermatofibrosarcoma protuberans is a fibrohistiocytic tumor of intermediate malignancy with aggressive localized growth, high recurrence rate, but low metastatic potential. It appears as a hardened plaque, with slow growth, upon which the development of nodules occurs. It predominates in the trunk and is unusual in acral locations. Histopathology reveals spindle cells with storiform pattern and cartwheel-like or whirlwind-like aspect. Immunohistochemistry shows positivity for CD34. The treatment is surgical. We report a case of long evolution, with an unusual location, that relapsed after surgery, to emphasize the importance of early diagnosis and proper treatment, avoiding aggressive resections with increased morbidity. PMID:24770523

Franco, Joanna Pimenta de Araujo; Barbosa, Caroline Cruz; da Fonseca, Bárbara Ferreira Saraiva; Lima, Ricardo Barbosa; D'Acri, Antônio Macedo; Martins, Carlos José

2014-01-01

394

[Diagnosis of meniscus damage].  

PubMed

Often, the clinical signs of an injured meniscus are not characteristic. The most reliable diagnostic tool in evaluation of meniscal damage is arthroscopy (diagnostic accuracy greater than 95%). It provides precise information on the nature and extent of a meniscal tear. The advent of arthroscopic surgery has favoured the use of endoscopy even as a diagnostic procedure. Arthrography is abandoned except in cases where arthroscopic meniscectomy is not feasible. As additional non-invasive examinations, magnetic resonance and ultrasound may be used; however, both methods are still not generally accepted and do not allow diagnosis and therapy as a one step procedure as does arthroscopy. PMID:3323722

Glinz, W

1987-01-01

395

Case for diagnosis*  

PubMed Central

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

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

2014-01-01

396

Using Genetic Testing to Guide Therapeutic Decisions in Cardiomyopathy  

PubMed Central

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

Lakdawala, Neal K

2013-01-01

397

Genetic Engineering  

Microsoft Academic Search

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

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

398

Human genetics  

SciTech Connect

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.

Carlson, E.A.

1984-01-01

399

Modern Genetics  

NSDL National Science Digital Library

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

The Concord Consortium

2012-01-13

400

Religious Traditions and Prenatal Genetic Counseling  

PubMed Central

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

Anderson, Rebecca Rae

2009-01-01

401

Genetic analysis in Bartter syndrome from India.  

PubMed

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

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

2014-10-01

402

Clinical review of genetic epileptic encephalopathies  

PubMed Central

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

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

2012-01-01

403

Parkinson's Disease: From Genetics to Clinical Practice  

PubMed Central

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

Clarimón, Jordi; Kulisevsky, Jaime

2013-01-01

404

Mitochondrial genetics  

PubMed Central

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

Chinnery, Patrick Francis; Hudson, Gavin

2013-01-01

405

[Laboratory diagnosis of a rare congenital neurodegenerative disease: cerebrotendinous xanthomatosis].  

PubMed

Cerebrotendinous xanthomatosis is a rare neurodegenerative disease characterized by the accumulation of cholesterol and cholestanol in the brain and the tendons caused by mutations of the gene encoding sterol 27-hydroxylase (CYP27A1), which is involved in bile acid synthesis. The diagnosis is often missed and delayed because of the variable clinical presentation of the disease. Blood testing for cerebrotendinous xanthomatosis is routinely performed using gas chromatography-mass spectrometry measurement of elevated cholestanol level, and the diagnosis is confirmed by molecular genetic analysis. Early recognition and initiation of chenodeoxycholic acid therapy with hydoxymethyl?glutaryl?Coenzyme-A reductase inhibitors is critical to prevent irreversible neurological damage and permanent disability. The authors summarize the current knowledge about the pathomechanism, laboratory diagnosis and therapeutic options of cerebrotendinous xanthomatosis. PMID:24836315

Varga, Viktória Evelin; Katkó, Mónika; Harangi, János; Balogh, István; Kapás, István; Madar, László; Seres, Ildikó; Molnár, Mária Judit; Paragh, György; Kovács, G Gábor; Harangi, Mariann

2014-05-25

406

Modeling the Diagnostic Criteria for Alcohol Dependence with Genetic Animal Models  

PubMed Central

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

Kendler, Kenneth S.; Hitzemann, Robert J.

2012-01-01

407

[Genetic diagnosis of leukemia: diagnosis of relapse and complete remission, and prediction of leukemia onset].  

PubMed

Wilms' tumor gene WT1 mRNA is a new marker of leukemic blast cells for AML, ALL, and CML. Minimal residual disease(MRD) of leukemia can be detected at frequencies as low as 1 in 10(3) to 10(4) normal bone marrow cells and 1 in 10(5) normal peripheral blood mononuclear cells by means of the quantitation of WT1 mRNA(WT1 assay) using reverse transcriptase-polymerase chain reaction. Thus, the WT1 assay makes it possible to rapidly assess the effectiveness of treatment and to evaluate the degree of eradication of leukemic cell in individual leukemia patients. Furthermore, WT1 assay can continuously assess the disease progression of myelodysplastic syndromes(MDS) and predict the evolution of MDS to overt AML within 6 months. PMID:10804819

Sugiyama, H

2000-02-01

408

Genetic modifiers of Huntington's disease.  

PubMed

Huntington's disease (HD) is a devastating neurodegenerative disorder that directly affects more than 1 in 10,000 persons in Western societies but, as a family disorder with a long, costly, debilitating course, it has an indirect impact on a far greater proportion of the population. Although some palliative treatments are used, no effective treatment exists for preventing clinical onset of the disorder or for delaying its inevitable progression toward premature death, approximately 15 years after diagnosis. Huntington's disease involves a movement disorder characterized by chorea, as well as a variety of psychiatric disturbances and intellectual decline, with a gradual loss of independence. A dire need exists for effective HD therapies to alleviate the suffering and costs to the individual, family, and health care system. In past decades, genetics, the study of DNA sequence variation and its consequences, provided the tools to map the HD gene to chromosome 4 and ultimately to identify its mutation as an expanded CAG trinucleotide repeat in the coding sequence of a large protein, dubbed huntingtin. Now, advances in genetic technology offer an unbiased route to the identification of genetic factors that are disease-modifying agents in human patients. Such genetic modifiers are expected to highlight processes capable of altering the course of HD and therefore to provide new, human-validated targets for traditional drug development, with the goal of developing rational treatments to delay or prevent onset of HD clinical signs. PMID:25154728

Gusella, James F; MacDonald, Marcy E; Lee, Jong-Min

2014-09-15

409

Diagnosis of syphilis*  

PubMed Central

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

Luger, A.

1981-01-01

410

Differential diagnosis of epilepsy.  

PubMed

Elements relevant to differential diagnosis between epileptic seizure and non-epileptic seizure as a consequence of syncope, cardiac arrhythmia or pseudoepilepsy are reviewed and discussed. Our experience with long-term monitoring of closed circuit TV-EEG of 136 medically refractory seizure patients showed that (a) about 19% have pseudoepileptic seizures, (b) only 36% of those verified pseudoepileptic seizure patients had epileptic seizures as well, and (c) 77% of pseudoepileptic seizures mimicked aspects of complex partial seizures. Pseudoepileptic seizures were not suspected by referring clinicians in the majority of cases, while a small but significant number of patients with verified complex partial seizures were suspected of having pseudoepileptic seizures. Failure to identify these non-epileptic seizures has serious medical and psychosocial implications and, therefore, astute clinical judgment is necessary in the differential diagnosis of epilepsy. Despite some technical limitations inherent in its current practice, the judicious use of long-term monitoring significantly enhances the quality of such judgment upon which the development of a management approach most meaningful to those medically refractory patients and society depends. PMID:3924564

Wada, J A

1985-01-01

411

Early diagnosis of leptospirosis.  

PubMed

A 25-years old man from Zagreb, Croatia, was admitted to the University Hospital for Infectious Diseases four days after the onset of symptoms such as fever, intense pain in the calves and anuria. The patient owned a rabbit and, before the onset of the disease, repaired some rubber pipes damaged by rodents. At admission, he had a severe clinical picture with fever, hypotension, jaundice, immobility, and pain in leg muscles. Treatment with ceftriaxone was initiated in combination with volume restitution. Renal failure soon ensued. Consequently continuous venovenous hemodiaphiltration therapy was performed. Due to acute respiratory distress syndrome, the patient was mechanically ventilated. The patient's condition gradually improved and he recovered fully from multi-organ failure. Diagnosis was confirmed by a microscopic agglutination test (MAT) covering 15 leptospira serovars and real-time polymerase-chain reaction (PCR). The first serum sample taken on day 6 tested negative for leptospira, while PCR showed positive results for leptospiral DNA. The second serum sample taken on day 13 tested positive for serovar Canicola serogroup Canicola, serovar Patoc, serovar Grippotyphosa serogroup Grippotyphosa and serovar Tarassovi serogroup Tarassovi (titre 4000, 4000, 1000 and 2000, respectively), while PCR was negative. This report highlights the benefits of combining MAT and PCR methods in early diagnosis of leptospirosis. PMID:25002958

Babic-Erceg, Andrea; Karlovic-Martinkovic, Diana; Santini, Marija; Persic, Zdenka; Vilibic-Cavlek, Tatjana

2014-05-13

412

Bayesian sequential change diagnosis  

E-print Network

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

Dayanik, Savas; Poor, H Vincent

2007-01-01

413

Proteomics in Molecular Diagnosis: Typing of Amyloidosis  

PubMed Central

Amyloidosis is a group of disorders caused by deposition of misfolded proteins as aggregates in the extracellular tissues of the body, leading to impairment of organ function. Correct identification of the causal amyloid protein is absolutely crucial for clinical management in order to avoid misdiagnosis and inappropriate, potentially harmful treatment, to assess prognosis and to offer genetic counselling if relevant. Current diagnostic methods, including antibody-based amyloid typing, have limited ability to detect the full range of amyloid forming proteins. Recent investigations into proteomic identification of amyloid protein have shown promise. This paper will review the current state of the art in proteomic analysis of amyloidosis, discuss the suitability of techniques based on the properties of amyloidosis, and further suggest potential areas of development. Establishment of mass spectrometry aided amyloid typing procedures in the pathology laboratory will allow accurate amyloidosis diagnosis in a timely manner and greatly facilitate clinical management of the disease. PMID:22131817

Loo, Dorothy; Mollee, Peter N.; Renaut, Patricia; Hill, Michelle M.

2011-01-01

414

Etiology, Pathogenesis, and Diagnosis of Interstitial Cystitis  

PubMed Central

Interstitial cystitis (IC) is a bladder syndrome of unknown etiology. The cause of IC is most likely multifactorial and includes genetic and environmental factors. Various pathophysiological changes in the bladder, pelvis, and peripheral and central nervous systems have been identified, and this has led to the emergence of biologically specific treatment modalities. Interstitial cystitis is being diagnosed with increasing frequency; however, current diagnostic criteria are non-uniform, and there is significant overlap between chronic pelvic pain syndromes in men and women, interstitial cystitis, recurrent “cystitis,” and the overactive bladder syndrome. The diagnosis of interstitial cystitis can be made clinically and by cystoscopy and hydrodistension. The sensitivity and specificity of urinary markers and the potassium sensitivity test have not been prospectively studied. PMID:16986036

Sant, Grannum R

2002-01-01

415

Secure Medical Diagnosis Using Rule Based Mining  

NASA Astrophysics Data System (ADS)

Security is the governing dynamics of all walks of life. Here we propose a secured medical diagnosis system. Certain specific rules are specified implicitly by the designer of the expert system and then symptoms for the diseases are obtained from the users and by using the pre defined confidence and support values we extract a threshold value which is used to conclude on a particular disease and the stage using Rule Mining. "THINK" CAPTCHA mechanism is used to distinguish between the human and the robots thereby eliminating the robots and preventing them from creating fake accounts and spam's. A novel image encryption mechanism is designed using genetic algorithm to encrypt the medical images thereby storing and sending the image data in a secured manner.

Saleem Durai, M. A.; Sriman Narayana Iyengar, N. Ch.

416

Diagnosis of Invasive Fungal Disease  

Microsoft Academic Search

\\u000a The diagnosis of invasive fungal infections (IFI) relies on the critical assessment of clinical presentation, associated risk\\u000a factors, and careful interpretation of the appropriate diagnostic tests. Frequently, clinicians have to initiate antifungal\\u000a therapy based on their clinical suspicion and without having made a definitive diagnosis, particularly in cancer or other\\u000a critically ill patients. To complicate diagnosis, isolation of fungal organisms

Dionissios Neofytos; Kieren Marr

417

DIAGNOSIS NUMBER OF CASES CARDIOVASCULAR  

E-print Network

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

Schladow, S. Geoffrey

418

Genetic toxicology.  

PubMed

Systems for testing genetic toxicology are components of carcinogenic and genetic risk assessment. Present routine genotoxicity-testing is based on at least 20 years of development during which many different test systems have been introduced and used. Today, it is clear that no single test is capable of detecting all genotoxic agents. Therefore, the usual approach is to perform a standard battery of in-vitro and in-vivo tests for genotoxicity. Work-groups of the European Union (EU), the Organization for Economic Co-operation and Development (OECD), and, very recently, the work-group of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) have defined such standard battery tests. These and some currently used supplementary or confirmatory tests are briefly discussed here. Additional test systems for the assessment of genotoxic and carcinogenic hazard and risk are seriously needed. These tests must be more relevant to man than are current assays and less demanding in respect of cost, time and number of animals. Another aspect for reassessment derives from the actual situation in the pharmaceutical industry. Companies have to prepare for the world economy of the 21st century. Therefore, pharmaceutical research is speeding up tremendously by use of tools such as genomics, combinatorial chemistry, high throughput screening and proteomics. Toxicology and genotoxicology need to re-evaluate their changing environment and must find ways to respond to these needs. In conclusion, genetic toxicology needs to answer questions coming from two major directions: hazard and risk identification and high throughput testing. PMID:9625484

Kramer, P J

1998-04-01

419

Photobacteriosis: Prevention and Diagnosis  

PubMed Central

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

2014-01-01

420

Diagnosis of Food Allergy  

PubMed Central

Diagnosis of food allergy can be challenging. Given the limited specificity of available allergy tests, these need to be interpreted in light of pre-test probability that is determined by a careful history. Using likelihood ratios calculated from previous publication may allow a more individualized assessment. This approach is likely to be most useful in patients with low to moderate results, below the 95% positive predictive value for that food. This review covers the diagnostic approach of immunoglobulin E-mediated food allergy. We first focus on the pre-test clinical assessment of a patient with a suspected food allergy. We then compare currently available diagnostic tests and discuss their performance for frequent food allergens. Finally, we conclude with the interpretation of allergy tests in light of the pre-test assessment to determine final probability of food allergy and indications for referral to an allergy specialist for food challenge. PMID:23718238

Bégin, Philippe; Nadeau, Kari C.

2014-01-01

421

Hybrid Systems Diagnosis  

NASA Technical Reports Server (NTRS)

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

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

2005-01-01

422

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

E-print Network

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 ...

Nazeen, Sumaiya

2014-01-01

423

Genetics Home Reference: Myopathy with deficiency of iron-sulfur cluster assembly enzyme  

MedlinePLUS

... Myopathy with deficiency of iron-sulfur cluster assembly enzyme On this page: Description Genetic changes Inheritance Diagnosis ... myopathy with deficiency of iron-sulfur cluster assembly enzyme? Myopathy with deficiency of iron-sulfur cluster assembly ...

424

[Diagnosis of bacterial vaginosis].  

PubMed

Bacterial vaginosis is a common, complex clinical syndrome characterized by alterations in the normal vaginal flora. When symptomatic, it is associated with a malodorous vaginal discharge and on occasion vaginal burning or itching. Under normal conditions, lactobacilli constitute 95% of the bacteria in the vagina. Bacterial vaginosis is associated with severe reduction or absence of the normal H2O2-producing lactobacilli and overgrowth of anaerobic bacteria and Gardnerella vaginalis, Atopobium vaginae, Mycoplasma hominis and Mobiluncus species. Most types of infectious disease are diagnosed by culture, by isolating an antigen or RNA/DNA from the microbe, or by serodiagnosis to determine the presence of antibodies to the microbe. Therefore, demonstration of the presence of an infectious agent is often a necessary criterion for the diagnosis of the disease. This is not the case for bacterial vaginosis, since the ultimate cause of the disease is not yet known. There are a variety of methods for the diagnosis of bacterial vaginosis but no method can at present be regarded as the best. Diagnosing bacterial vaginosis has long been based on the clinical criteria of Amsel, whereby three of four defined criteria must be satisfied. Nugent's scoring system has been further developed and includes validation of the categories of observable bacteria structures. Up-to-date molecular tests are introduced, and better understanding of vaginal microbiome, a clear definition for bacterial vaginosis, and short-term and long-term fluctuations in vaginal microflora will help to better define molecular tests within the broader clinical context. PMID:24073569

Djuki?, Slobodanka; ?irkovi?, Ivana; Arsi?, Biljana; Garaleji?, Eliana

2013-01-01

425

Celiac disease: Prevalence, diagnosis, pathogenesis and treatment  

PubMed Central

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

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

2012-01-01

426

Pathogenesis, diagnosis, and management of cholangiocarcinoma.  

PubMed

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

Rizvi, Sumera; Gores, Gregory J

2013-12-01

427

Diagnosis and management of Alzheimer's disease.  

PubMed

The diagnosis of Alzheimer's disease (AD) is a 2-stage process, in stage 1, the dementia syndrome, comprising neuropsychologic and neuropsychiatrie components together with deficits in activities of daily living, is differentiated on clinical grounds from a number of other conditions (delirium, concomitant physical illness, drug treatment normal memory loss, etc), in stage 2, the cause is determined, AD being the most common, followed by vascular dementia, Lewy-body dementia, frontal lobe dementia, and a host of so-called secondary causes. Although a mixed Alzheimer/vascular picture is common, gradual onset of multiple cognitive deficits is typical of AD, while abrupt onset, a fluctuating course, hypertension, and focal neurologic signs suggest vascular dementia, in Lewy-body dementia, memory loss may not be an early feature, and fluctuation can be marked by distressing psychotic symptoms and behavioral disturbance, investigations should be minimally invasive and relatively cheap, confined to routine blood tests, chest x-ray and/or electrocardiogram if clinically indicated, cardiologie or neurologic referral in the presence of cerebrovascular signs, and computed tomography if an intracranial lesion is suspected. Accurate diagnosis enables the clinician to outline the disease course to the family and inform them of genetic implications. Numerous instruments for assessing cognitive function, global status, psychiatric well-being, and activities of daily living are briefly reviewed. PMID:22034134

Burns, A

2000-06-01

428

Molecular Cytogenetic Diagnosis and Somatic Genome Variations  

PubMed Central

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

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

2010-01-01

429

[Advanced molecular technologies for the diagnosis of congenital malformation in neonates].  

PubMed

Congenital malformation is one of the most frequent causes of infant death in western countries and major cities in China. Though genetic screening of newborns remains a hot issue and concern, the mortality rate associated with birth defects has not been significantly reduced over the past 20 years. Many genetic diseases manifest symptoms during the first 28 days of life, but full clinical symptoms might not be evident in newborns. Moreover, genetic aberrations is highly heterogeneous. These complicated factors lead to the establishment of diagnosis based on nonspecific or obscure symptoms. Recently developed array comparative genomic hybridization (CGH) and next generation sequencing (NGS) techniques with efficient high-resolution allow to screening of the entire genome for DNA copy number variants and sequencing respectively. These new and powerful tools can shorten the differential diagnosis process and quicken to movement towards targeted treatment and genetic and prognostic counseling. PMID:24229588

Yang, Lin; Wang, Hui-Jun; Huang, Guo-Ying; Zhou, Wen-Hao

2013-11-01

430

Reliable confidence measures for medical diagnosis with evolutionary algorithms.  

PubMed

Conformal Predictors (CPs) are machine learning algorithms that can provide predictions complemented with valid confidence measures. In medical diagnosis, such measures are highly desirable, as medical experts can gain additional information for each machine diagnosis. A risk assessment in each prediction can play an important role for medical decision making, in which the outcome can be critical for the patients. Several classical machine learning methods can be incorporated into the CP framework. In this paper, we propose a CP that makes use of evolved rule sets generated by a genetic algorithm (GA). The rule-based GA has the advantage of being human readable. We apply our method on two real-world datasets for medical diagnosis, one dataset for breast cancer diagnosis, which contains data gathered from fine needle aspirate of breast mass; and one dataset for ovarian cancer diagnosis, which contains proteomic patterns identified in serum. Our results on both datasets show that the proposed method is as accurate as the classical techniques, while it provides reliable and useful confidence measures. PMID:21062682

Lambrou, Antonis; Papadopoulos, Harris; Gammerman, Alex

2011-01-01

431

Pediatric bipolar disorder: validity, phenomenology, and recommendations for diagnosis  

PubMed Central

Objective To find, review, and critically evaluate evidence pertaining to the phenomenology of pediatric bipolar disorder and its validity as a diagnosis. Methods The present qualitative review summarizes and synthesizes available evidence about the phenomenology of bipolar disorder (BD) in youths, including description of the diagnostic sensitivity and specificity of symptoms, clarification about rates of cycling and mixed states, and discussion about chronic versus episodic presentations of mood dysregulation. The validity of the diagnosis of BD in youths is also evaluated based on traditional criteria including associated demographic characteristics, family environmental features, genetic bases, longitudinal studies of youths at risk of developing BD as well as youths already manifesting symptoms on the bipolar spectrum, treatment studies and pharmacologic dissection, neurobiological findings (including morphological and functional data), and other related laboratory findings. Additional sections review impairment and quality of life, personality and temperamental correlates, the clinical utility of a bipolar diagnosis in youths, and the dimensional versus categorical distinction as it applies to mood disorder in youths. Results A schema for diagnosis of BD in youths is developed, including a review of different operational definitions of `bipolar not otherwise specified.' Principal areas of disagreement appear to include the relative role of elated versus irritable mood in assessment, and also the limits of the extent of the bipolar spectrum – when do definitions become so broad that they are no longer describing `bipolar' cases? Conclusions In spite of these areas of disagreement, considerable evidence has amassed supporting the validity of the bipolar diagnosis in children and adolescents. PMID:18199237

Youngstrom, Eric A; Birmaher, Boris; Findling, Robert L

2013-01-01

432

Importance of genetic evaluation and testing in pediatric cardiomyopathy.  

PubMed

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

Tariq, Muhammad; Ware, Stephanie M

2014-11-26

433

Importance of genetic evaluation and testing in pediatric cardiomyopathy  

PubMed Central

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

Tariq, Muhammad; Ware, Stephanie M

2014-01-01

434

Diagnosis and management of primary ciliary dyskinesia.  

PubMed

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder with defective structure and/or function of motile cilia/flagella, causing chronic upper and lower respiratory tract infections, fertility problems, and disorders of organ laterality. Diagnosing PCD requires a combined approach utilizing characteristic phenotypes and complementary methods for detection of defects of ciliary function and ultrastructure, measurement of nasal nitric oxide and genetic testing. Currently, biallelic mutations in 31 different genes have been linked to PCD allowing a genetic diagnosis in approximately ~?60% of cases. Management includes surveillance of pulmonary function, imaging, and microbiology of upper and lower airways in addition to daily airway clearance and prompt antibiotic treatment of infections. Early referral to specialized centers that use a multidisciplinary approach is likely to improve outcomes. Currently, evidence-based knowledge on PCD care is missing let alone management guidelines. Research and clinical investigators, supported by European and North American patient support groups, have joined forces under the name of BESTCILIA, a European Commission funded consortium dedicated to improve PCD care and knowledge. Core programs of this network include the establishment of an international PCD registry, the generation of disease specific PCD quality of life questionnaires, and the first randomized controlled trial in PCD. PMID:25610612

Werner, Claudius; Onnebrink, Jörg Große; Omran, Heymut

2015-01-01

435

The porphyrias: advances in diagnosis and treatment  

PubMed Central

The inborn errors of heme biosynthesis, the porphyrias, are 8 genetically distinct metabolic disorders that can be classified as “acute hepatic,” “hepatic cutaneous,” and “erythropoietic cutaneous” diseases. Recent advances in understanding their pathogenesis and molecular genetic heterogeneity have led to improved diagnosis and treatment. These advances include DNA-based diagnoses for all the porphyrias, new understanding of the pathogenesis of the acute hepatic porphyrias, identification of the iron overload-induced inhibitor of hepatic uroporphyrin decarboxylase activity that causes the most common porphyria, porphyria cutanea tarda, the identification of an X-linked form of erythropoietic protoporphyria due to gain-of-function mutations in erythroid-specific 5-aminolevulinate synthase (ALAS2), and new and experimental treatments for the erythropoietic prophyrias. Knowledge of these advances is relevant for hematologists because they administer the hematin infusions to treat the acute attacks in patients with the acute hepatic porphyrias, perform the chronic phlebotomies to reduce the iron overload and clear the dermatologic lesions in porphyria cutanea tarda, and diagnose and treat the erythropoietic porphyrias, including chronic erythrocyte transfusions, bone marrow or hematopoietic stem cell transplants, and experimental pharmacologic chaperone and stem cell gene therapies for congenital erythropoietic protoporphyria. These developments are reviewed to update hematologists on the latest advances in these diverse disorders. PMID:22791288

Balwani, Manisha

2012-01-01

436

Diagnosis of metabolic bone disease  

Microsoft Academic Search

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

P. Grech; T. J. Martin; N. A. Barrington; P. J. Ell; I. FOGELMAN

1986-01-01

437

Ordered Diagnosis #SpringerVerlag  

E-print Network

, abductive reasoning can be used to perform diagnosis [21, 3]. Rules in the fault model specify causeOrdered Diagnosis c #Springer­Verlag Davy Van Nieuwenborgh # and Dirk Vermeir ## Dept. of Computer fault model, between the various knowledge sources. It turns out that the seman­ tics for ordered logic

Vermeir, Dirk

438

Diagnosis of amyotrophic lateral sclerosis  

Microsoft Academic Search

This review of the differential diagnosis of amyotrophic lateral sclerosis focuses on two themes. The first is practical, how to establish the diagnosis based primarily on clinical findings buttressed by electrodiagnosis. The main considerations are multifocal motor neuropathy and cervical spondylotic myelopathy. The second theme is the relationship of motor neuron disease to other conditions, including benign fasciculation (Denny–Brown, Foley

Lewis P Rowland

1998-01-01

439

Genetic markers to predict polygenic disease  

Microsoft Academic Search

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

David J. Galton

1999-01-01

440

Sclerosing bone dysplasias: genetic and radioclinical features  

Microsoft Academic Search

.   Although knowledge of basic genetics in the field of sclerosing bone dysplasias is progressing, the radiologist still plays\\u000a a pivotal role in the diagnosis of this relatively poorly understood group of disorders. Based on a target site approach,\\u000a these anomalies are classified into three groups. Within each group, further differentiation can be made by distinctive clinical\\u000a findings and by

F. M. Vanhoenacker; L. H. De Beuckeleer; W. Van Hul; W. Balemans; G. J. Tan; S. C. Hill; A. M. De Schepper

2000-01-01

441

Current and future applications of genetics in primary care medicine.  

PubMed

Individualized medical treatment and prevention based on one's genetic makeup are promises likely to be fulfilled over decades. Already family history is taking a more prominent role in preventive care. Primary care clinicians and geneticists will increasingly collaborate to diagnose and manage genetic conditions: both single-gene disorders and multifactorial diseases such as infections,cancers, cardiovascular disease and mental illness. This will require society, with primary care clinicians in the forefront, to implement means for efficient family history-taking; maintaining private, personally accessible genetic health records; safeguarding people from genetic discrimination; distributing access to scarce genetic specialists and expensive technologies; rectifying lay misconceptions about inheritance; managing emotional responses and family dynamics related to genetic diagnosis; and motivating people at increased familial risk to take preventive action. PMID:15331241

Acheson, Louise S; Wiesner, Georgia L

2004-09-01

442

Age-related macular degeneration – clinical review and genetics update  

PubMed Central

Age-related macular degeneration (AMD) is the leading cause of central vision impairment in persons over the age of 50 years in developed countries. Both genetic and non-genetic (environmental) factors play major roles in AMD etiology, and multiple gene variants and lifestyle factors such as smoking have been associated with the disease. While dissecting the basic etiology of the disease remains a major challenge, current genetic knowledge has provided opportunities for improved risk assessment, molecular diagnosis and clinical testing of genetic variants in AMD treatment and management. This review addresses the potential of translating the wealth of genetic findings for improved risk prediction and therapeutic intervention in AMD patients. Finally, we discuss the recent advancement in genetics and genomics and the future prospective of personalized medicine in AMD patients. PMID:23713713

Ratnapriya, R; Chew, E Y

2013-01-01

443

Genetic contributions to pain: a review of findings in humans  

PubMed Central

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

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

2009-01-01

444

Expert recommendations for the laboratory diagnosis of MPS VI.  

PubMed

Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disease caused by a deficiency of N-acetylgalactosamine 4-sulfatase (arylsulfatase B, ASB). This enzyme is required for the degradation of dermatan sulfate. In its absence, dermatan sulfate accumulates in cells and is excreted in large quantities in urine. Specific therapeutic intervention is available; however, accurate and timely diagnosis is crucial for maximal benefit. To better understand the current practices for diagnosis and to establish diagnostic guidelines, an international MPS VI laboratory diagnostics scientific summit was held in February of 2011 in Miami, Florida. The various steps in the diagnosis of MPS VI were discussed including urinary glycosaminoglycan (uGAG) analysis, enzyme activity analysis, and molecular analysis. The following conclusions were reached. Dilute urine samples pose a significant problem for uGAG analysis and MPS VI patients can be missed by quantitative uGAG testing alone as dermatan sulfate may not always be excreted in large quantities. Enzyme activity analysis is universally acknowledged as a key component of diagnosis; however, several caveats must be considered and the appropriate use of reference enzymes is essential. Molecular analysis supports enzyme activity test results and is essential for carrier testing, subsequent genetic counseling, and prenatal testing. Overall the expert panel recommends caution in the use of uGAG screening alone to rule out or confirm the diagnosis of MPS VI and acknowledges enzyme activity analysis as a critical component of diagnosis. Measurement of another sulfatase enzyme to exclude multiple sulfatase deficiency was recommended prior to the initiation of therapy. When feasible, the use of molecular testing as part of the diagnosis is encouraged. A diagnostic algorithm for MPS VI is provided. PMID:22405600

Wood, T; Bodamer, O A; Burin, M G; D'Almeida, V; Fietz, M; Giugliani, R; Hawley, S M; Hendriksz, C J; Hwu, W L; Ketteridge, D; Lukacs, Z; Mendelsohn, N J; Miller, N; Pasquali, M; Schenone, A; Schoonderwoerd, K; Winchester, B; Harmatz, P

2012-05-01

445

Applying the New Genetics  

ERIC Educational Resources Information Center

New developments in the prediction and treatment of genetic diseases are presented. Genetic counseling and the role of the counselor, and rights of individuals to reproduce versus societal impact of genetic disorders, are discussed. (RW)

Sorenson, James

1976-01-01

446

Genetic Screening Debate  

MedlinePLUS Videos and Cool Tools

... the lower right-hand corner of the player. Genetic Screening Debate HealthDay November 13, 2014 Related MedlinePlus Pages Cancer Genetic Testing Transcript As genetic testing becomes more widely ...

447

Reimbursement for Genetic Testing  

MedlinePLUS

... Financial Planning Who Should I Tell? Genetic Testing & Counseling Compensation for Genetic Testing Whole Genome Sequencing Screening vs. Testing What Is Genetic Counseling? Participating in Research Disease Research Patient Privacy Clinical ...

448

Genetic Testing for ALS  

MedlinePLUS

... a person will develop symptoms of ALS. Genetic Counseling If there is more than one person with ... testing based on your concerns and values. Genetic counseling does not always lead to genetic testing. For ...

449

EMQN Best Practice Guidelines for molecular and haematology methods for carrier identification and prenatal diagnosis of the haemoglobinopathies.  

PubMed

Haemoglobinopathies constitute the commonest recessive monogenic disorders worldwide, and the treatment of affected individuals presents a substantial global disease burden. Carrier identification and prenatal diagnosis represent valuable procedures that identify couples at risk for having affected children, so that they can be offered options to have healthy offspring. Molecular diagnosis facilitates prenatal diagnosis and definitive diagnosis of carriers and patients (especially 'atypical' cases who often have complex genotype interactions). However, the haemoglobin disorders are unique among all genetic diseases in that identification of carriers is preferable by haematological (biochemical) tests rather than DNA analysis. These Best Practice guidelines offer an overview of recommended strategies and methods for carrier identification and prenatal diagnosis of haemoglobinopathies, and emphasize the importance of appropriately applying and interpreting haematological tests in supporting the optimum application and evaluation of globin gene DNA analysis.European Journal of Human Genetics advance online publication, 23 July 2014; doi:10.1038/ejhg.2014.131. PMID:25052315

Traeger-Synodinos, Joanne; Harteveld, Cornelis L; Old, John M; Petrou, Mary; Galanello, Renzo; Giordano, Piero; Angastioniotis, Michael; De la Salle, Barbara; Henderson, Shirley; May, Alison

2014-07-23

450

Targeted next generation sequencing for molecular diagnosis of Usher syndrome.  

PubMed

BackgroundUsher syndrome is an autosomal recessive disease that associates sensorineural hearing loss, retinitis pigmentosa and, in some cases, vestibular dysfunction. It is clinically and genetically heterogeneous. To date, 10 genes have been associated with the disease, making its molecular diagnosis based on Sanger sequencing, expensive and time-consuming. Consequently, the aim of the present study was to develop a molecular diagnostics method for Usher syndrome, based on targeted next generation sequencing.MethodsA custom HaloPlex panel for Illumina platforms was designed to capture all exons of the 10 known causative Usher syndrome genes (MYO7A, USH1C, CDH23, PCDH15, USH1G, CIB2, USH2A, GPR98, DFNB31 and CLRN1), the two Usher syndrome-related genes (HARS and PDZD7) and the two candidate genes VEZT and MYO15A. A cohort of 44 patients suffering from Usher syndrome was selected for this study. This cohort was divided into two groups: a test group of 11 patients with known mutations and another group of 33 patients with unknown mutations.ResultsForty USH patients were successfully sequenced, 8 USH patients from the test group and 32 patients from the group composed of USH patients without genetic diagnosis. We were able to detect biallelic mutations in one USH gene in 22 out of 32 USH patients (68.75%) and to identify 79.7% of the expected mutated alleles. Fifty-three different mutations were detected. These mutations included 21 missense, 8 nonsense, 9 frameshifts, 9 intronic mutations and 6 large rearrangements.ConclusionsTargeted next generation sequencing allowed us to detect both point mutations and large rearrangements in a single experiment, minimizing the economic cost of the study, increasing the detection ratio of the genetic cause of the disease and improving the genetic diagnosis of Usher syndrome patients. PMID:25404053

Aparisi, María J; Aller, Elena; Fuster-García, Carla; García-García, Gema; Rodrigo, Regina; Vázquez-Manrique, Rafael P; Blanco-Kelly, Fiona; Ayuso, Carmen; Roux, Anne-Françoise; Jaijo, Teresa; Millán, José M

2014-11-18

451

Procreative beneficence: why we should select the best children.  

PubMed

Eugenic selection of embryos is now possible by employing in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD). While PGD is currently being employed for the purposes of detecting chromosomal abnormalities or inherited genetic abnormalities, it could in principle be used to test any genetic trait such as hair colour or eye colour. Genetic research is rapidly progressing into the genetic basis of complex traits like intelligence and a gene has been identified for criminal behaviour in one family. Once the decision to have IVF is made, PGD has few 'costs' to couples, and people would be more inclined to use it to select less serious medical traits, such as a lower risk of developing Alzheimer Disease, or even for non-medical traits. PGD has already been used to select embryos of a desired gender in the absence of any history of sex-linked genetic disease. I will argue that: (1) some non-disease genes affect the likelihood of us leading the best life; (2) we have a reason to use information which is available about such genes in our reproductive decision-making; (3) couples should select embryos or fetuses which are most likely to have the best life, based on available genetic information, including information about non-disease genes. I will also argue that we should allow selection for non-disease genes even if this maintains or increases social inequality. I will focus on genes for intelligence and sex selection. I will defend a principle which I call Procreative Beneficence: couples (or single reproducers) should select the child, of the possible children they could have, who is expected to have the best life, or at least as good a life as the others, based on the relevant, available information. PMID:12058767

Savulescu, J

2001-10-01

452

Genetics Home Reference: What is genetic testing?  

MedlinePLUS

... Chromosomes Handbook Glossary Resources Handbook Table of Contents Cells and DNA How Genes Work Mutations and Health Inheritance Consultation Testing Therapy Human Genome Project Genomic Research Next Handbook > Genetic Testing > What is genetic ...

453

Bronchoscopic diagnosis of pneumonia.  

PubMed Central

Lower respiratory tract infections are characterized by significant morbidity and mortality but also by a relative inability to establish a specific etiologic agent on clinical grounds alone. With the recognized shortcomings of expectorated or aspirated secretions toward establishing an etiologic diagnosis, clinicians have increasingly used bronchoscopy to obtain diagnostic samples. A variety of specimen types may be obtained, including bronchial washes or brushes, protected specimen brushings, bronchoalveolar lavage, and transbronchial biopsies. Bronchoscopy has been applied in three primary clinical settings, including the immunocompromised host, especially human immunodeficiency virus-infected and organ transplant patients; ventilator-associated pneumonia; and severe, nonresolving community- or hospital-acquired pneumonia in nonventilated patients. In each clinical setting, and for each specimen type, specific laboratory protocols are required to provide maximal information. These protocols should provide for the use of a variety of rapid microscopic and quantitative culture techniques and the use of a variety of specific stains and selective culture to detect unusual organism groups. PMID:7834604

Baselski, V S; Wunderink, R G

1994-01-01

454

Diagnosis of autoimmune pancreatitis.  

PubMed

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

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

2014-11-28

455

Avian toxicologic diagnosis  

USGS Publications Warehouse

This chapter describes the sources and pathophysiology of some potential poisons that affect birds and summarizes useful laboratory tests. The diagnosis of poisoning in birds, as in mammals, requires a complete and accurate history, careful observation of clinical signs, and a thorough necropsy evaluation. Appropriate sample handling and analysis, based on consultation with the diagnostic toxicologist, are critical (Table 19--1). Veterinary toxicology laboratories are becoming increasingly specialized, with only certain laboratories capable of analyzing for drug residues or anticoagulants, for example. Although a local laboratory may not be able to fulfill a specific test request, they may recommend an alternative laboratory or may be willing to forward the sample. As a general rule in suspect poisoning cases, large tissue samples of liver, kidney, brain, and subcutaneous fat and of crop, proventriculus, and ventriculus contents should be collected at necropsy and frozen. Appropriate samples should be submitted frozen, with the remainder held in the freezer for possible later testing. A second set of tissues should be placed in 10% formalin for histopathologic examination.

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

2000-01-01

456

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

PubMed Central

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

Schipper, Erica; Nezhat, Camran

2012-01-01

457

Genetically engineered foods  

MedlinePLUS

... chap 105. Committee on Identifying and Assessing Unintended Effects of Genetically Engineered Foods on Human Health, National Research Council. Safety of genetically engineered foods: Approaches to ...

458

Foundations Algorithm Components Numerical Optimization Genetic Programming Genetic Algorithms  

E-print Network

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

Kjellström, Hedvig

459

Foundations Algorithm Components Numerical Optimization Genetic Programming Genetic Algorithms  

E-print Network

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

Kjellström, Hedvig

460

Psychiatric genetic testing: attitudes and intentions among future users and providers.  

PubMed

Psychiatric genetic research may eventually render possible psychiatric genetic testing. Whereas all genetic knowledge has certain characteristics raising ethical, legal, and social issues, psychiatric genetic knowledge adds more controversial issues. Ethical principles have been proposed as a guide in this field, but the optimal utilization of genetic testing has also been recognized to depend on knowledge of the potential consumers' attitudes. To provide knowledge to inform the public debate on mental illness and genetics, and the future conducting of psychiatric genetic testing and counseling, we surveyed attitudes toward psychiatric genetic testing among 397 patients with a psychiatric diagnosis, 164 of their relatives and 100 medical and psychology students. The results showed widespread interest in psychiatric genetic testing of self and child, but less support for prenatal testing. Psychiatric and somatic genetic testing attracted the same amounts of accept. General attitudes toward access to psychiatric genetic testing and information revealed substantial support for bioethical principles of autonomy and privacy. However, questions describing more specific situations revealed contradictions mirroring the bioethical dilemmas recognized in the field and variations in attitudes between groups with different levels of knowledge of genetics, different kinds of experience with mental illness, and different motives and preconceptions regarding psychiatric genetics. The contradictions and differences in attitudes among possible future users and providers of psychiatric genetic testing and counseling indicate ambivalence, insecurity, and perceived lack of knowledge in relation to psychiatric genetics. These results should inform further research and the future integration of psychiatric genetics into practice. PMID:18023043

Laegsgaard, Mett Marri; Mors, Ole

2008-04-01

461

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

PubMed

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

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