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1

Changing indications for preimplantation genetic diagnosis (PGD)  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) is an attractive addition to prenatal genetic diagnosis. Not only were traditional PGD indications valid, but newer indications should be envisioned. The major new indication is aneuploidy testing by PGD for transfer of euploid embryos. This could increase fertilization success in ART, and extend to couples experiencing repeated IVF failures or repeated spontaneous abortions. Other novel

Joe Leigh Simpson

2001-01-01

2

Current concepts in preimplantation genetic diagnosis (PGD): a molecular biologist's view  

Microsoft Academic Search

The first clinically applied preimplantation genetic diagnosis (PGD) was reported more than a decade ago and since then PGD has known an exponential growth. This first report described the use of PCR to sex embryos from couples at risk for X-linked diseases. Not surprisingly, in the first years, the development of PCR-based tests led to PGD for well-known monogenic diseases

Karen Sermon

2002-01-01

3

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

4

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

Microsoft Academic Search

The regulation of reproductive medicine technologies differs significantly among Western industrialized countries. In Germany, preimplantation genetic diagnosis (PGD) is prohibited due to the Embryo Protection Act, which came into force in 1991. In the last 5 years, this prohibition has been vigorously debated. In the present studies, which are part of the German research programme on ethical implications of the

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

2005-01-01

5

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.

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

2010-01-01

6

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

7

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

8

Preimplantation genetic diagnosis (PGD) for nonsyndromic deafness by polar body and blastomere biopsy  

Microsoft Academic Search

Purpose  Development of an efficient and reliable PGD protocol for nonsyndromic deafness, by polar body (PB) and blastomere PGD.\\u000a \\u000a \\u000a \\u000a Methods  The GJB2\\/GJB6 mutations along with 12 polymorphic markers were used in PGD analysis of blastomeres or polar bodies in 14 couples\\u000a for 35 cycles. Marker informativity, diagnosis rates, Allele Drop Out (ADO) rates and PB1 heterozygosity rates were assessed.\\u000a \\u000a \\u000a \\u000a Results  Six cycles were

Gheona Altarescu; Talia Eldar-Geva; Baruch Brooks; Edith Zylber-Haran; Irit Varshaver; Ehud J. Margalioth; Ephrat Levy-Lahad; Paul Renbaum

2009-01-01

9

Multiplex PCR combining deltaF508 mutation and intragenic microsatellites of the CFTR gene for pre-implantation genetic diagnosis (PGD) of cystic fibrosis  

Microsoft Academic Search

One major limitation of pre-implantation genetic diagnosis (PGD) practice comes from the need to develop single cell PCR protocols. For a disease such as cystic fibrosis (CF), for which almost 1000 mutations have been identified, the development of a mutation based PGD protocol is impracticable. An elegant way to overcome this problem is to set up an indirect diagnosis using

Céline Moutou; Nathalie Gardes; Stéphane Viville

2002-01-01

10

Vitrified blastocysts from Preimplantation Genetic Diagnosis (PGD) as a source for human Embryonic Stem Cell (hESC) derivation.  

PubMed

Embryos diagnosed as abnormal in Preimplantation Genetic Diagnosis (PGD) cycles are useful for the establishment of human Embryonic Stem Cells (hESC) lines with genetic disorders. These lines can be helpful for drug screening and for the development of new treatments. Vitrification has proved to be an efficient method to preserve human blastocysts. One hundred and three abnormal or undiagnosed vitrified blastocysts from the PGD programme at Institut Universitari Dexeus were donated for human embryonic stem cell derivation. The overall survival rate after warming was 70.6 %. Our results showed better survival rates when blastocysts have not started the hatching process (initial/expanded 87.8 %, hatching 68.3 % and hatched 27.3 %). Thirty-five blastocysts and 12 partially surviving embryos were seeded. One hESC line with the multiple exostoses type 2 paternal mutation was obtained. PMID:22735930

Aran, Begoña; Sole, Miquel; Rodriguez-Pizà, Ignasi; Parriego, Mònica; Muñoz, Yolanda; Boada, Montserrat; Barri, Pere N; Izpisúa, Juan Carlos; Veiga, Anna

2012-06-27

11

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

PubMed

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

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

2013-02-06

12

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

PubMed

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

Grazi, Richard V; Wolowelsky, Joel B

13

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

Microsoft Academic Search

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

Richard V. Grazi; Joel B. Wolowelsky

2006-01-01

14

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

15

Preimplantation genetic diagnosis (PGD) for SHOX-related haploinsufficiency in conjunction with trisomy 21 detection by molecular analysis  

Microsoft Academic Search

Purpose  Development of a molecular PGD protocol for a male with an X-linked deletion in the SHOX gene region, located in the pseudoautosomal\\u000a region of the X\\/Y chromosomes. Due to excessive recombination in this region, the deletion can be found in male offspring.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We developed a 13 marker multiplex fluorescent PCR protocol: 3 markers within the deleted SHOX region, 5 flanking

Gheona Altarescu; Orit Reish; Paul Renbaum; Ester Kasterstein; Dvorah Komarovsky; Alisa Komsky; Orna Bern; Dvorah Strassburger; Ephrat Levy-Lahad; Raphael Ron-El

2011-01-01

16

Current features of preimplantation genetic diagnosis  

Microsoft Academic Search

More than 4000 preimplantation genetic diagnosis (PGD) cycles have been performed, suggesting that PGD may no longer be considered a research activity. The important present feature of PGD is its expansion to a variety of conditions, which have never been considered as an indication for prenatal diagnosis, including the late-onset disorders with genetic predisposition and preimplantation non-disease testing, with the

Anver Kuliev; Yury Verlinsky

2002-01-01

17

Preimplantation Genetic Diagnosis  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) can provide genetic information on embryos obtained through in vitro fertilization (IVF), allowing implantation of embryos identified as unaffected with a given genetic or chromosomal disorder. With the availability of increasingly sophisticated genetic testing, its use has advanced from the selection of female embryos for the prevention of X-linked genetic diseases to testing for single gene

Lora K. Shahine; Aaron B. Caughey

2005-01-01

18

Preimplantation genetic diagnosis  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) is an evolving technique that provides a practical alternative to prenatal diagnosis and termination of pregnancy for couples who are at substantial risk of transmitting a serious genetic disorder to their offspring. Samples for genetic testing are obtained from oocytes or cleaving embryos after in vitro fertilization. Only embryos that are shown to be free of

Susan Pickering; Frances Flinter; Caroline Mackie Ogilvie; Peter Braude

2002-01-01

19

Taskforce 5: preimplantation genetic diagnosis.  

PubMed

The European Society of Human Reproduction and Embryology (ESHRE) Ethics Task Force sets out a recommended multidisciplinary approach to the application of preimplantation genetic diagnosis (PGD). The statement includes consideration of fundamental ethical principles, specific problems in cases of high genetic risk, and PGD for aneuploidy screening, HLA typing and sex selection for non-medical reasons. PMID:12615840

Shenfield, F; Pennings, G; Devroey, P; Sureau, C; Tarlatzis, B; Cohen, J

2003-03-01

20

Preimplantation genetic diagnosis with HLA matching  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) has recently been offered in combination with HLA typing, which allowed a successful haematopoietic reconstitution in affected siblings with Fanconi anaemia by transplantation of stem cells obtained from the HLA-matched offspring resulting from PGD. This study presents the results of the first PGD practical experience performed in a group of couples at risk for producing children

Svetlana Rechitsky; Anver Kuliev; Illan Tur-Kaspa; Randy Morris; Yury Verlinsky

2004-01-01

21

Preimplantation Genetic Diagnosis of Inherited Cancer: Familial Adenomatous Polyposis Coli  

Microsoft Academic Search

Purpose:Our purpose was to achieve preimplantation genetic diagnosis (PGD) of the dominant cancer predisposition syndrome, familial adenomatous polyposis coli (FAPC), as an alternative to prenatal diagnosis.

Asangla Ao; Dagan Wells; Alan H. Handyside; Robert M. L. Winston; Joy D. A. Delhanty

1998-01-01

22

Preimplantation Genetic Diagnosis (Embryo Screening) for Enlarged Vestibular Aqueduct due to SLC26A4 Mutation  

Microsoft Academic Search

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 ?-thalassemia, the application of PGD to hereditary hearing impairment has not

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

2010-01-01

23

PGD for cystic fibrosis patients and couples at risk of an additional genetic disorder combined with 24-chromosome aneuploidy testing.  

PubMed

Preimplantation genetic diagnosis (PGD) for inherited disorders is presently applied for more than 300 different conditions. The most frequent PGD indication is cystic fibrosis (CF), the largest series of which is reviewed here, totalling 404 PGD cycles. This involved testing for 52 different CFTR mutations with almost half of the cases (195/404 cycles) performed for ?F508 mutation, one-quarter (103/404 cycles) for six other frequent mutations and only a few for the remaining 45 CFTR mutations. There were 44 PGD cycles performed for 25 CF-affected homozygous or double-heterozygous CF patients (18 male and seven female partners), which involved testing simultaneously for three mutations, resulting in birth of 13 healthy CF-free children and no misdiagnosis. PGD was also performed for six couples at a combined risk of producing offspring with CF and another genetic disorder. Concomitant testing for CFTR and other mutations resulted in birth of six healthy children, free of both CF and another genetic disorder in all but one cycle. A total of 96 PGD cycles for CF were performed with simultaneous aneuploidy testing, including microarray-based 24-chromosome analysis, as a comprehensive PGD for two or more conditions in the same biopsy material. PMID:23523379

Rechitsky, Svetlana; Verlinsky, Oleg; Kuliev, Anver

2013-01-29

24

Preimplantation genetic diagnosis: State of the art  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) is used to analyze embryos genetically before their transfer into the uterus. It was developed first in England in 1990, as part of progress in reproductive medicine, genetic and molecular biology. PGD offers couples at risk the chance to have an unaffected child, without facing termination of pregnancy. Embryos are obtained by in vitro fertilization with

Claire Basille; René Frydman; Abdelwahab El Aly; Laetitia Hesters; Renato Fanchin; Gérard Tachdjian; Julie Steffann; Marc LeLorc’h; Nelly Achour-Frydman

2009-01-01

25

Preimplantation genetic diagnosis.  

PubMed

Preimplantation genetic diagnosis (PGD) has now been used in human fertility centers for a decade. To this end, diagnostic analysis is conducted on polar bodies or single blastomeres from biopsied embryos before the embryos are transferred, allowing the selection of normal embryos before a pregnancy has been established. Advances in technology available for PGD are described, including fluorescent in situ hybridization (FISH), interphase chromosome conversion, comparative genomic hybridization (CGH), fluorescent polymerase chain reaction (PCR), multiplex PCR, and whole genome amplification. These techniques support the diagnosis of a number of diseases at the single-cell level. PMID:12112960

Ouhibi, N; Olson, S; Patton, P; Wolf, D

2001-10-01

26

Preimplantation genetic diagnosis: patients' experiences and attitudes  

Microsoft Academic Search

BACKGROUND: This study aims to report the experiences and attitudes of patients who have undergone preimplantation genetic diagnosis (PGD). The extent to which this technique is acceptable to the individuals for whom it is intended is relatively unexplored, and remains a crucial issue that may ultimately determine the value of PGD as an alternative to prenatal diagnosis in high-risk couples.

S. A. Lavery; R. Aurell; C. Turner; C. Castellu; A. Veiga; P. N. Barri; R. M. Winston

2002-01-01

27

Clinical Value of Preimplantation Genetic Diagnosis  

Microsoft Academic Search

The clinical application of preimplantation genetic diagnosis (PGD) has provided an alternative approach for the prevention of affected pregnancies in couples at high reproductive risk. The frequent contribution of genetic factors to infertility problems makes PGD of particular value for assisted reproductive practices. In addition, the selection of euploid embryos for transfer has a strong impact on IVF efficiency as

L Gianaroli; M. C Magli; F Fiorentino; M Baldi; A. P Ferraretti

2003-01-01

28

Outcome of preimplantation genetic diagnosis of translocations  

Microsoft Academic Search

Objective: To review 35 cases of preimplantation genetic diagnosis (PGD) of translocations with several methods, including telomeric probes.Design: Retrospective study.Setting: Clinical IVF laboratory.Patient(s): Thirty-five couples with one partner carrying a chromosomal translocation.Intervention(s): PGD of translocation after polar-body or embryo biopsy.Main Outcome Measure(s): Pregnancy outcome.Result(s): Several trends were observed. First, PGD can achieve a statistically significant reduction in spontaneous abortion, from

Santiago Munné; Mireia Sandalinas; Tomas Escudero; Jingly Fung; Luca Gianaroli; Jacques Cohen

2000-01-01

29

Preimplantation genetic diagnosis for cancer predisposition  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) has recently been offered for couples with an inherited predisposition for late onset disorders. This paper presents the results of PGD for a group of couples at risk for producing children with cancer predisposition. Using a standard IVF procedure, oocytes or embryos were tested for different mutations predisposing to cancer, preselecting and transferring only mutation-free embryos

Svetlana Rechitsky; Oleg Verlinsky; Anna Chistokhina; Tatyana Sharapova; Seckin Ozen; Christina Masciangelo; Anver Kuliev; Yury Verlinsky

2002-01-01

30

Preimplantation genetic diagnosis in the mirror of ethics  

Microsoft Academic Search

Summary  \\u000a Legal and moral considerations hinder the introduction of preimplantation genetic diagnosis (PGD) in Germany. This article\\u000a presents and discusses the ethical arguments for and against PGD. In the autor's view neither the fact that PGD is not a well\\u000a established technique nor the danger that single-cell-analysis may lead to misdiagnosis convincingly demonstrates that PGD\\u000a is morally inacceptable. Inconsistencies in

Christian Netzer

1999-01-01

31

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

32

Advances in preimplantation genetic diagnosis  

Microsoft Academic Search

Strategies for preimplantation genetic diagnosis (PGD) have become increasingly complex. For single gene disorders it is now usual for several DNA fragments to be simultaneously amplified using multiplex-PCR. This allows redundant diagnostic loci to be analyzed, reducing the chance of misdiagnosis due to allele dropout (ADO). Additionally, hypervariable ‘fingerprinting’ loci can be amplified, revealing the presence of DNA contaminants. Chromosomal

Dagan Wells

2004-01-01

33

Preimplantation genetic diagnosis: present and future  

Microsoft Academic Search

Purpose: Preimplantation genetic diagnosis (PGD) was developed more than a decade ago and aims to identify embryos free of genetic\\u000a disease attributed either to gene mutations or chromosome errors. The purpose of this article is to provide an update on the\\u000a current status and future prospects of PGD.\\u000a \\u000a \\u000a Methods: Review of studies employing different strategies for the detection of single

Elpida Fragouli

2007-01-01

34

Strategies and clinical outcome of 250 cycles of Preimplantation Genetic Diagnosis for single gene disorders  

Microsoft Academic Search

BACKGROUND: We report on our experience with preimplantation genetic diagnosis (PGD) for single gene disorders (SGDs), from 1999 to 2004, describing strategies and overall clinical outcome of 250 cycles in 174 couples for 23 different genetic conditions. METHODS: PGD cycles included 15 for autosomal dominant, 148 for autosomal recessive and 19 for X-linked SGDs. In addition, 68 cycles of PGD

F. Fiorentino; A. Biricik; A. Nuccitelli; R. De Palma; S. Kahraman; M. Iacobelli; V. Trengia; D. Caserta; M. A. Bonu; A. Borini; M. Baldi

2005-01-01

35

Improved implantation after preimplantation genetic diagnosis of aneuploidy  

Microsoft Academic Search

The objective of this study was to assess the improvement in implantation rates after preimplantation genetic diagnosis (PGD) of numerical abnormalities for the sole indication of advanced maternal age when compared with a control group. Each PGD patient was matched to a control patient according to several parameters prior to obtaining pregnancy results. The diagnosis was based on the analysis

Santiago Munné; Mireia Sandalinas; Tomas Escudero; Esther Velilla; Renee Walmsley; Sasha Sadowy; Jacques Cohen; David Sable

2003-01-01

36

Ethical issues in new uses of preimplantation genetic diagnosis  

Microsoft Academic Search

The use of preimplantation genetic diagnosis (PGD) to screen embryos for aneuploidy and genetic disease is grow- ing. New uses of PGD have been reported in the past year for screening embryos for susceptibility to cancer, for late-onset diseases, for HLA-matching for existing children, and for gender. These extensions have raised questions about their ethical acceptability and the adequacy of

John A. Robertson

37

Preimplantation genetic diagnosis in cattle: a review.  

PubMed

Preimplantation Genetic Diagnosis (PGD) is reviewed and novel fields where it may be applied are investigated. Technical advances of PGD in cattle embryos have already enabled its integration as a part of the MOET (Multiple Ovulation Embryo Transfer) breeding system. PGD for well-defined selection targets can enhance cattle breeding and embryo trade. It allows embryo selection according to their sex, and it may be used to breed special cow lines, or top bulls, by selecting embryos for valuable production traits using Marker Assisted Selection (MAS). A good allelic profile and/or the insertion of a transgene can be detected by PGD. This review article presents the technical requirements for PGD, and shows that this biotechnological method has great economic potential. PMID:11402695

Bodó, S; Baranyai, B; Gócza, E; Dohy, J; Markkula, M

2001-01-01

38

Preimplantation genetic diagnosis for Down syndrome pregnancy  

Microsoft Academic Search

Objective  To evaluate the effect of preimplantation genetic diagnosis (PGD) conducted for women who had Down syndrome pregnancy previously.\\u000a \\u000a \\u000a \\u000a Methods  Trisomy 21 was diagnosed by using fluorescence in site hybridization (FISH) before embryo transfer in two women who had Down\\u000a syndrome pregnancies. Each received one or two PGD cycles respectively.\\u000a \\u000a \\u000a \\u000a Results  Case 1: one PGD cycle was conducted, two oocytes were fertilized and

Yu Zhang; Chen-ming Xu; Yi-min Zhu; Min-yue Dong; Yu-li Qian; Fan Jin; He-feng Huang

2007-01-01

39

Psychological impact of preimplantation genetic diagnosis: a review of the literature  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) was first reported as successful in humans in the early 1990s and nearly two decades later the psychological impact of PGD has not yet been clearly defined. As PGD requires the use of IVF, this paper provides a brief summary of literature related to the various psychological aspects of IVF followed by a review of the

J. C. Karatas; K. A. Strong; K. Barlow-Stewart; C. McMahon; B. Meiser; C. Roberts

2010-01-01

40

Prognostic role of preimplantation genetic diagnosis for aneuploidy in assisted reproductive technology outcome  

Microsoft Academic Search

BACKGROUND: Preimplantation genetic diagnosis (PGD) for aneuploidy is recommended to couples at risk of generating chromosomally abnormal embryos. The aim of this study was to demonstrate that PGD for aneuploidy has an important role in the prognosis of subsequent treatments. METHODS: A total of 389 couples underwent their first PGD for aneuploidy due to either female age >38 years (n

A. P. Ferraretti; M. C. Magli; L. Kopcow; L. Gianaroli

2004-01-01

41

Can preimplantation genetic diagnosis improve success rates in recurrent aborters with translocations?  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) for people suffering recurrent miscarriages is increasingly being performed worldwide. However, there is limited information on whether PGD can improve success rates in translocation carriers. We therefore compared pregnancy outcomes between PGD and natural pregnancy cases, reviewing the clinical research data- base. No improvement in the success rate at the first oocyte retrieval was evident in

Mayumi Sugiura-Ogasawara; Kaoru Suzumori

2005-01-01

42

First Successful Preimplantation Genetic Diagnosis in Singapore - Avoidance of ?-Thalassaemia Major  

Microsoft Academic Search

Introduction: We report on the fi rst successful preimplantation genetic diagnosis (PGD) in Singapore. Clinical Picture: A couple who are ?-thalassaemia carriers and have an affected daughter requested for PGD. Treatment: Two cycles of PGD were performed on the couple. ?-thalassaemia mutations were detected using a nested PCR and minisequencing strategy, and unaffected embryos were selected for transfer. Outcome: A

Christine Yap; Wen Wang; Mui Nee Lim; Samuel S Chong

43

Prenatal diagnosis yes, preimplantation genetic diagnosis no: a contradictory stance?  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) after IVF with subsequent selection of embryos is accepted and practised in a number of European countries. In others, it is not only controversial but also forbidden by law. Since in these countries prenatal diagnosis (PND) with subsequent termination of pregnancy is legal and widely practised, a consistency problem arises. How can the discrepancy in regulation

Dieter Birnbacher

2007-01-01

44

Preimplantation genetic diagnosis for gender selection in the United States  

Microsoft Academic Search

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

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

2009-01-01

45

Knowledge and attitudes towards preimplantation genetic diagnosis in Germany  

Microsoft Academic Search

BACKGROUND: Preimplantation genetic diagnosis (PGD) is a technique which is often related to emotional debates because of its ethical and social implications. Worldwide there are different forms of legislation; Germany constitutes an interesting case because of the historical background concerning eugenics and dealing with handi- capped persons at the time of national socialism. PGD is currently not legal but there

U. Meister; C. Finck; Y. Stobel-Richter; G. Schmutzer; E. Brahler

2004-01-01

46

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

47

Clinical application of multiple displacement amplification in preimplantation genetic diagnosis  

Microsoft Academic Search

Multiple displacement amplification (MDA) is a technique used in the amplification of very small amounts of DNA. MDA is reported to yield large quantities of high-quality DNA. The applicability of MDA to single cells was recently demonstrated as a potential technique for preimplantation genetic diagnosis (PGD). This paper shows the first clinical application of MDA in PGD. Two cycles of

Ali Hellani; Serdar Coskun; Abdelghhani Tbakhi; Saad Al-Hassan

2005-01-01

48

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

Microsoft Academic Search

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

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

2001-01-01

49

Preimplantation Genetic Diagnosis for Gender Selection in the United States.  

National Technical Information Service (NTIS)

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 w...

G. Olivera J. Weier L. Silver P. Colls T. Escudero

2009-01-01

50

Preimplantation genetic diagnosis: State of the ART 2011  

Microsoft Academic Search

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

Joyce C. Harper; Sioban B. SenGupta

51

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

52

Predictability of preimplantation genetic diagnosis of aneuploidy and translocations on prospective attempts  

Microsoft Academic Search

The aim of this study was to determine if the outcomes of aneuploidy and translocation testing by preimplantation genetic diagnosis (PGD) at the 8-cell stage have a predictive value for new genetic diagnosis cycles. In total, 83 cycles (39 patients) undergoing PGD of translocations and 378 cycles (176 patients) of aneuploidy were included. Predictability, defined as having similar rate (±20%)

S Munné; T Escudero; P Colls; Z Xuezhong; M Oter; M Garrisi; F Barnes; C Zouves; L Werlin; C Magli; J Cohen

2004-01-01

53

Over a decade of experience with preimplantation genetic diagnosis  

Microsoft Academic Search

The three respondents provide additional support for preimplantation genetic diagnosis (PGD) having the pivotal place it now has in prenatal genetic diagnosis: chromosomal abnormalities (e.g., unbalanced translocations), Mendelian disorders, and HLA typing for transfer of compatible, genetically normal, embryos. Transferring euploid embryos has decreased the clinical abortion rate and increased the implantation rate in assisted reproductive technologies (ART), but it

Yury Verlinsky; Jacques Cohen; Santiago Munne; Luca Gianaroli; Joe Leigh Simpson; Anna Pia Ferraretti; Anver Kuliev

2004-01-01

54

Social sex selection by preimplantation genetic diagnosis  

Microsoft Academic Search

A personal view is presented, exploring the issue of social sex selection by preimplantation genetic diagnosis from the dual perspectives of protecting the autonomy of the couple and the professional duty of care. It is concluded that sex selection by PGD is acceptable in certain circumstances.

Marcus Pembrey

2002-01-01

55

Social sex selection by preimplantation genetic diagnosis.  

PubMed

A personal view is presented, exploring the issue of social sex selection by preimplantation genetic diagnosis from the dual perspectives of protecting the autonomy of the couple and the professional duty of care. It is concluded that sex selection by PGD is acceptable in certain circumstances. PMID:12470579

Pembrey, Marcus

56

Preimplantation genetic diagnosis of structural abnormalities  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) of translocations can be achieved through a variety of methods. For female carriers, a possibility is by polar body biopsy and analysis of its metaphase chromosomes using painting probes. For male carriers or female carriers with terminal breakpoints, metaphase chromosomes can also be studied by fusing blastomeres to enucleated oocytes. Otherwise, interphase analysis of the translocation

Santiago Munne ´

2001-01-01

57

Preimplantation genetic diagnosis of pericentric inversions  

Microsoft Academic Search

Inversions are structural chromosome abnormalities that may be associated with infertility, multiple miscarriage and chromosomally unbalanced offspring. Preimplantation genetic diagnosis (PGD) with subtelomeric probes was used to select for transfer only those embryos that were normal or balanced for three pericentric inversions. In contrast to previous protocols the present procedure allows the detection of unbalanced embryos that might arise from

Michael Lee; John Stevens; Mireia Sandalinas

2001-01-01

58

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

Microsoft Academic Search

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

Timothy Krahn

2009-01-01

59

Whole genome amplification in preimplantation genetic diagnosis  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) refers to a procedure for genetically analyzing embryos prior to implantation, improving\\u000a the chance of conception for patients at high risk of transmitting specific inherited disorders. This method has been widely\\u000a used for a large number of genetic disorders since the first successful application in the early 1990s. Polymerase chain reaction\\u000a (PCR) and fluorescent in situ

Ying-ming Zheng; Ning Wang; Lei Li; Fan Jin

2011-01-01

60

Preimplantation genetic diagnosis: state of the art.  

PubMed

Preimplantation genetic diagnosis (PGD) is used to analyze embryos genetically before their transfer into the uterus. It was developed first in England in 1990, as part of progress in reproductive medicine, genetic and molecular biology. PGD offers couples at risk the chance to have an unaffected child, without facing termination of pregnancy. Embryos are obtained by in vitro fertilization with intracytoplasmic sperm injection (ICSI), and are biopsied mostly on day 3; blastocyst biopsy is mentioned as a possible alternative. The genetic analysis is performed on one or two blastomeres, by fluorescent in situ hybridization (FISH) for cytogenetic diagnosis, or polymerase chain reaction (PCR) for molecular diagnosis. Genetic analysis of the first or second polar body can be used to study maternal genetic contribution. Only unaffected embryos are transferred into the uterus. To improve the accuracy of the diagnosis, new technologies are emerging, with comparative genomic hybridization (CGH) and microarrays. In Europe, depending on national regulations, PGD is either prohibited, or allowed, or practiced in the absence of recommendations. The indications are chromosomal abnormalities, X-linked diseases or single gene disorders. The number of disorders being tested increases. In Europe, data collection from the year 2004 reports that globally 69.6% of cycles lead to embryo transfer and implantation rate is 17%. European results from the year 2004 show a clinical pregnancy rate of 18% per oocyte retrieval and 25% per embryo transfer, leading to 528 babies born. The cohort studies concerning the paediatric follow-up of PGD babies show developmental outcomes similar to children conceived after IVF-ICSI. Recent advances include human leucocyte antigen (HLA) typing for PGD embryos, when an elder sibling is affected with a genetic disorder and needs stem cell transplantation. The HLA-matched offspring resulting can give cord blood at birth. Preimplantation genetic screening (PGS) consists in euploid embryo selection; it could be used for advanced maternal age, repeated implantation failure, single embryo transfer or idiopathic recurrent pregnancy loss. These applications are controversial. PGD for inherited cancer predispositions is discussed and social sexing remains prohibited in Europe. PGD requires a close collaboration between obstetricians, fertility specialists, IVF laboratory and human geneticists. It needs intensive effort, expensive techniques and is demanding for the patients, but it offers tremendous opportunity for couples whose previous child has exhibited genetic abnormalities. The debate on certain indications is ongoing. PMID:19411132

Basille, Claire; Frydman, René; El Aly, Abdelwahab; Hesters, Laetitia; Fanchin, Renato; Tachdjian, Gérard; Steffann, Julie; LeLorc'h, Marc; Achour-Frydman, Nelly

2009-05-02

61

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

PubMed

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

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

2008-06-03

62

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

Microsoft Academic Search

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

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

2008-01-01

63

A CASE FOR GOVERNMENT SPONSORED MONITORING OF PREIMPLANTATION GENETIC DIAGNOSIS IN THE UNITED STATES  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD), a modified version of in vitro fertilization in which individual embryos are screened for specific genetic characteristics prior to implantation, provides a powerful way for parents suffering from infertility to increase their chances of having healthy children. In its various forms, PGD allows parents to screen for gender, providing a means for avoiding X-linked diseases, chromosomal

Aaron D. Levine

64

Preimplantation genetic diagnosis of haemophilia.  

PubMed

Preimplantation genetic diagnosis (PGD) aims to increase the number of options available to couples who could have a child affected with haemophilia and reduce the anxiety these couples often associate with reproduction. The female partner must undergo an in vitro fertilization cycle, and the eggs or embryos are then biopsied. Embryos which are unaffected by haemophilia can then be transferred to the uterus. The clear advantage of this technique is that the woman knows from the very beginning that the pregnancy is unaffected by haemophilia, and she can avoid conventional invasive prenatal diagnosis and the difficult decision on whether or not to terminate an affected pregnancy. Several strategies for this single cell genetic diagnosis have been described. These include embryonic sexing using polymerase chain reaction, embryonic sexing using fluorescent in situ hybridization, specific diagnosis using restriction enzymes, sequencing and haplotype analysis. Over the years, PGD has attracted much ethical commentary, both supportive and critical, regarding the fundamental principles of embryo selection and destruction. New scientific advances and their potential applications are considered. PMID:19036080

Lavery, Stuart

2008-11-22

65

Preimplantation genetic diagnosis--an overview.  

PubMed

Since the early 1990s, preimplantation genetic diagnosis (PGD) has been expanding in scope and applications. Selection of female embryos to avoid X-linked disease was carried out first by polymerase chain reaction, then by fluorescence in situ hybridization (FISH), and an ever-increasing number of tests for monogenic diseases have been developed. Couples with chromosome rearrangements such as Robertsonian and reciprocal translocations form a large referral group for most PGD centers and present a special challenge, due to the large number of genetically unbalanced embryos generated by meiotic segregation. Early protocols used blastomeres biopsied from cleavage-stage embryos; testing of first and second polar bodies is now a routine alternative, and blastocyst biopsy can also be used. More recently, the technology has been harnessed to provide PGD-AS, or aneuploidy screening. FISH probes specific for chromosomes commonly found to be aneuploid in early pregnancy loss are used to test blastomeres for aneuploidy, with the aim of replacing euploid embryos and increasing pregnancy rates in groups of women who have poor IVF success rates. More recent application of PGD to areas such as HLA typing and social sex selection have stoked public controversy and concern, while provoking interesting ethical debates and keeping PGD firmly in the public eye. PMID:15749997

Ogilvie, Caroline Mackie; Braude, Peter R; Scriven, Paul N

2005-03-01

66

Whole genome amplification in preimplantation genetic diagnosis*  

PubMed Central

Preimplantation genetic diagnosis (PGD) refers to a procedure for genetically analyzing embryos prior to implantation, improving the chance of conception for patients at high risk of transmitting specific inherited disorders. This method has been widely used for a large number of genetic disorders since the first successful application in the early 1990s. Polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH) are the two main methods in PGD, but there are some inevitable shortcomings limiting the scope of genetic diagnosis. Fortunately, different whole genome amplification (WGA) techniques have been developed to overcome these problems. Sufficient DNA can be amplified and multiple tasks which need abundant DNA can be performed. Moreover, WGA products can be analyzed as a template for multi-loci and multi-gene during the subsequent DNA analysis. In this review, we will focus on the currently available WGA techniques and their applications, as well as the new technical trends from WGA products.

Zheng, Ying-ming; Wang, Ning; Li, Lei; Jin, Fan

2011-01-01

67

The Benefits of Preimplantation Genetic Diagnosis for Chromosomal Aneuploidy  

Microsoft Academic Search

\\u000a Despite recent controversy, preimplantation genetic diagnosis (PGD) for aneuploidies is becoming a practical means in assisted\\u000a reproduction technology (ART) to select embryos with higher developmental potential for improving in vitro fertilization (IVF)\\u000a effectiveness. Available PGD experience for chromosomal disorders shows that at least half of the oocytes and embryos obtained\\u000a from poor prognosis IVF patients are aneuploid and clearly should

Anver Kuliev; Yury Verlinsky

68

Extending preimplantation genetic diagnosis: medical and non-medical uses.  

PubMed

New uses of preimplantation genetic diagnosis (PGD) to screen embryos prior to transfer raise ethical, legal, and policy issues that deserve close attention. Extensions for medical purposes, such as to identify susceptibility genes, late onset disease, and human leukocyte antigen (HLA) matching, are usually ethically acceptable. Whether embryo screening for gender, perfect pitch, or other non-medical characteristics are also acceptable depends upon the parental needs served and the harm posed to embryos, children, and society. Speculations about potential future uses of PGD should not prevent otherwise acceptable current uses of PGD. PMID:12930852

Robertson, J A

2003-08-01

69

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

Microsoft Academic Search

Although morally acceptable in theory, preimplantation genetic diagnosis (PGD) for mitochondrial DNA (mtDNA) disorders raises several ethical questions in clinical practice. This paper discusses the major conditions for good clinical practice. Our starting point is that PGD for mtDNA mutations should as far as possible be embedded in a scientific research protocol. For every clinical application of PGD for mtDNA

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

2009-01-01

70

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

PubMed Central

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

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

2013-01-01

71

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

Microsoft Academic Search

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

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

2001-01-01

72

The beneficial effects of preimplantation genetic diagnosis for aneuploidy support extensive clinical application  

Microsoft Academic Search

The aim of this study was to evaluate the clinical impact of preimplantation genetic diagnosis (PGD) for aneuploidy on 193 patients who subsequently achieved 208 clinical pregnancies, in relation to their reproductive history. The 208 clinical pregnancies included in the study resulted from 1029 assisted conception cycles in combination with PGD for aneuploidy in 740 couples with a history of

Luca Gianaroli; M Cristina Magli; Anna P Ferraretti; Carla Tabanelli; Vincenzo Trengia; Valeria Farfalli; Giorgio Cavallini

2005-01-01

73

Preimplantation genetic diagnosis in Saudi Arabia.  

PubMed

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

Abotalib, Zeinab

2013-04-30

74

Preimplantation genetic diagnosis in Saudi Arabia  

PubMed Central

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

Abotalib, Zeinab

2013-01-01

75

Preimplantation genetic diagnosis: recent triumphs and remaining challenges.  

PubMed

Over the last 20 years, preimplantation genetic diagnosis (PGD) has changed from being an experimental procedure to one that is carried out in specialized diagnostic centers worldwide. Genetic awareness and the rapid identification of germline mutations or chromosomal abnormalities enable individuals to know their risk of transmitting a genetic disease before they have children. This has created a demand for PGD from couples who wish to avoid terminations of affected pregnancies. Although PGD is expensive because it requires couples to go through IVF, there is a trend for diagnosis to move towards automation, which will reduce cost and the need for specialized expertise. This will allow diagnosis to be carried out in routine molecular diagnostic laboratories. PMID:22845479

SenGupta, Sioban B; Delhanty, Joy D A

2012-07-01

76

Ethical aspects of pre-implantation genetic diagnosis  

Microsoft Academic Search

Pre-implantation genetic diagnosis (PGD) presents several ethical dilemmas, some akin to those found in prenatal diagnosis, and others more specific to the technique, which requires in-vitro fertilisation and creates embryos in vitro. Here, the status of the embryo is central to the dilemmas concerning its selection, possible destruction or use in research, and the fate of carrier embryos. Furthermore, the

Françoise Shenfield

2008-01-01

77

Extending preimplantation genetic diagnosis: the ethical debate. Ethical issues in new uses of preimplantation genetic diagnosis.  

PubMed

The use of preimplantation genetic diagnosis (PGD) to screen embryos for aneuploidy and genetic disease is growing. New uses of PGD have been reported in the past year for screening embryos for susceptibility to cancer, for late-onset diseases, for HLA-matching for existing children, and for gender. These extensions have raised questions about their ethical acceptability and the adequacy of regulatory structures to review new uses. This article describes current and likely future uses of PGD, and then analyses the ethical issues posed by new uses of PGD to screen embryos for susceptibility and late-onset conditions, for HLA-matching for tissue donation to an existing child, and for gender selection. It also addresses ethical issues that would arise in more speculative scenarios of selecting embryos for hearing ability or sexual orientation. The article concludes that except for sex selection of the first child, most current extensions of PGD are ethically acceptable, and provides a framework for evaluating future extensions for nonmedical purposes that are still speculative. PMID:12615807

Robertson, John A

2003-03-01

78

Preimplantation Genetic Diagnosis—An Overview  

Microsoft Academic Search

Since the early 1990s, preimplantation genetic diagnosis (PGD) has been expanding in scope and applications. Selection of female embryos to avoid X-linked disease was carried out first by polymerase chain reaction, then by fluorescence in situ hybridization (FISH), and an ever-increasing number of tests for monogenic diseases have been developed. Couples with chromosome rearrangements such as Robertsonian and reciprocal translocations

Caroline Mackie Ogilvie; Peter R. Braude; Paul N. Scriven

2005-01-01

79

Views of internists towards uses of PGD.  

PubMed

Preimplantation genetic diagnosis (PGD) is increasingly available, but how physicians view it is unclear. Internists are gatekeepers and sources of information, often treating disorders for which PGD is possible. This quantitative study surveyed 220 US internists, who were found to be divided. Many would recommend PGD for cystic fibrosis (CF; 33.7%), breast cancer (BRCA; 23.4%), familial adenomatous polyposis (FAP; 20.6%) and familial hypertrophic cardiomyopathy (19.9%), but few for social sex selection (5.2%); however, in each case, >50% were unsure. Of those surveyed, 4.9% have suggested PGD to patients. Only 7.1% felt qualified to answer patient questions about it. Internists who would refer for PGD had completed medical training less recently and, for CF, were more likely to have privately insured patients (P<0.033) and patients who reported genetic discrimination (P<0.013). Physicians more likely to refer for BRCA and FAP were less likely to have patients ask about genetic testing. This study suggests that internists often feel they have insufficient knowledge about it and may refer for PGD based on limited understanding. They view possible uses of PGD differently, partly reflecting varying ages of onset and disease treatability. These data have critical implications for training, research and practice. Preimplantation genetic diagnosis (PGD) allows embryos to be screened prior to transfer to a woman's womb for various genetic markers. This procedure raises complex medical, social, psychological and ethical issues, but how physicians view it is unclear. Internists are gatekeepers and sources of information, often treating disorders for which PGD use is possible. We surveyed 220 US internists, who were found to be divided: many would recommend PGD for cystic fibrosis (CF; 33.7%), breast cancer (BRCA; 23.4%), familial adenomatous polyposis (FAP; 20.6%), and familial hypertrophic cardiomyopathy (FHC; 19.9%) and a few for sex selection (5.2%); but in each case, >50% were unsure. Of those surveyed, 4.9% have suggested PGD to patients. Only 7.1% felt qualified to answer patient questions. Internists who would refer for PGD completed medical training less recently and, for CF, were more likely to have privately insured patients and patients who reported genetic discrimination. Physicians more likely to refer for BRCA and FAP were less likely to have patients ask about genetic testing. This quantitative study suggests that internists often feel they have insufficient knowledge and may refer for PGD based on limited understanding. They view possible uses of PGD differently, partly reflecting varying ages of onset and disease treatability. Internists should be made aware of the potential benefit of PGD, but also be taught to refer patients, when appropriate, to clinical geneticists who could then refer the patient to an IVF/PGD team. These data thus have critical implications for training, research and practice. PMID:23276655

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

2012-11-21

80

Single intragenic microsatellite preimplantation genetic diagnosis for cystic fibrosis provides positive allele identification of all CFTR genotypes for informative couples  

Microsoft Academic Search

This study is part of a strategy aimed at using fluorescent polymerase chain reaction (PCR) on informative genetic microsatellite markers as a diagnostic tool in preimplantation genetic diagnosis (PGD) of severe monogenic disease. Two couples, both of whom had previously had children who were compound heterozygote for severe cystic fibrosis mutations, were offered PGD using fluorescent PCR of the highly

I. Eftedal; M. Schwartz; H. Bendtsen; A. N. Andersen; S. Ziebe

2001-01-01

81

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

Microsoft Academic Search

In the UK, the Human Fertilisation and Embryology Authority (HFEA) is responsible for licensing preimplantation genetic diagnosis (PGD). To date, licenses have been issued for the testing of about 70 genetic conditions, drawing on three key ‘ethical principles’. Following a public consultation, the HFEA has recently widened the scope for PGD to include susceptibility to late onset, lower penetrance conditions

Clare Williams; Kathryn Ehrich; Bobbie Farsides; Rosamund Scott

2007-01-01

82

Preimplantation Genetic Diagnosis in Marfan Syndrome  

PubMed Central

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

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

2013-01-01

83

Polar body-based preimplantation genetic diagnosis for Mendelian disorders.  

PubMed

Introduced >20 years ago, the use of polar bodies (PBs), involving sequential removal and genetic analysis of the first (PB1) and second (PB2) PB, provides the option for pre-embryonic diagnosis, when the objection to the embryo biopsy procedures makes preimplantation genetic diagnosis (PGD) non-applicable. PB-based approach has presently been utilized in PGD for genetic and chromosomal disorders, applied either separately, or together with embryo biopsy approaches, especially if there are two or more PGD indications. We present here the world's largest experience of 938 PGD cycles for single-gene disorders performed by PB testing for 146 different monogenic conditions, which resulted in the birth of 345 healthy children (eight pregnancies are still ongoing), providing strong evidence that PB-based PGD is a reliable and safe procedure, with an extremely high accuracy rate of over 99%. With application of microarray technology, PB-based approach will be utilized for increasing number of indications, involving simultaneous testing for 24 chromosomes and single-gene disorders. PMID:21320873

Kuliev, Anver; Rechitsky, Svetlana

2011-02-14

84

Genetic control of 6-phosphogluconate dehydrogenase (6-PGD) isozymes in cultivated wheat and rye  

Microsoft Academic Search

The 6-phosphogluconate dehydrogenase (6-PGD) zymogram phenotypes of wheat, rye and their aneuploid derivatives were determined. Two genes involved in the production of 6-PGD isozymes were located on chromosome arms CRL (4 RL) and FRL (6 RL) of “Imperial” rye. On the basis of differential interactions between wheat and rye chromosomes, evidence was obtained that genes located on chromosomes 6 A,

S. L. K. Hsam; F. J. Zeller; W. Huber

1982-01-01

85

Provision and quality assurance of preimplantation genetic diagnosis in Europe  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) is now well established and provided in many European countries. However, regulations, professional standards and accreditation requirements can differ notably. Furthermore, no comprehensive independent data exist either about practice and provision in Europe or about the quality assurance practices and procedures designed to optimize the quality of the results. Consequently, a study was launched to obtain

Anniek Corveleyn; Michael A Morris; Elisabeth Dequeker; Karen Sermon; James Lawford Davies; Guillermo Antiñolo; Andreas Schmutzler; Jiri Vanecek; Nick Nagels; Eleni Zika; Francesc Palau; Dolores Ibarreta

2008-01-01

86

Extending preimplantation genetic diagnosis: medical and non-medical uses  

Microsoft Academic Search

New uses of preimplantation genetic diagnosis (PGD) to screen embryos prior to transfer raise ethical, legal, and policy issues that deserve close attention. Extensions for medical purposes, such as to identify susceptibility genes, late onset disease, and human leukocyte antigen (HLA) matching, are usually ethically acceptable. Whether embryo screening for gender, perfect pitch, or other non-medical characteristics are also acceptable

J A Robertson

2003-01-01

87

Sex selection and preimplantation genetic diagnosis at The Farah Hospital  

Microsoft Academic Search

The issue of sex selection by using preimplantation genetic diagnosis (PGD) for non-medical reasons has been the subject of heated debate. Although the ethical arguments regarding this subject are complex, we would like to extend and express some views based on practical experience, with a special focus on individual needs in developing countries, taking into consideration: social, cultural, religious, financial

Z Kilani; L Haj Hassan

2002-01-01

88

Preimplantation genetic diagnosis for gender selection in the USA  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) for gender selection for non-medical reasons has been considered an unethical procedure by several authors and agencies in the Western society on the basis that it could disrupt the sex ratio, that it discriminates against women and that it leads to disposal of normal embryos of the non-desired gender. In this study, the analysis of a

P Colls; L Silver; G Olivera; J Weier; T Escudero; N Goodall; G Tomkin; S Munné

2009-01-01

89

Preimplantation genetic diagnosis for retinoblastoma: the first reported liveborn  

Microsoft Academic Search

PurposeTo develop an accurate mutation analysis procedure for retinoblastoma gene (RB1) mutation, which is sensitive at the single-cell level, and to use in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD) to achieve pregnancies without retinoblastoma.

Kangpu Xu; Zev Rosenwaks; Katherine Beaverson; Ina Cholst; Lucinda Veeck; David H. Abramson

2004-01-01

90

Preimplantation Genetic Diagnosis: Choosing the “Good Enough” Child  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) raises serious moral questions concerning the parent-child relationship. Good parents accept their children unconditionally: they do not reject\\/attack them because they do not have the features they want. There is nothing wrong with treating a child as someone who can help promote some other worthwhile end, providing the child is also respected as an end in

Helen Watt

2004-01-01

91

Meiotic and mitotic nondisjunction: lessons from preimplantation genetic diagnosis  

Microsoft Academic Search

Direct testing of the outcome of the first and second meiotic divisions has become possible with the introduction of preimplantation genetic diagnosis (PGD) for aneuploidies. Testing of oocytes by fluorescent in situ hybridization (FISH) analysis of the first and second polar bodies showed that more than half of oocytes from the IVF patients aged 35 years and older had chromosomal

Anver Kuliev; Yury Verlinsky

2004-01-01

92

Preimplantation Genetic Diagnosis for Severe Albright Hereditary Osteodystrophy  

Microsoft Academic Search

Context: Preimplantation genetic diagnosis (PGD) enables the selection of embryos without mu- tations for implantation and has not been described to our knowledge for mutations in GNAS. Phocomelia in a patient with Albright hereditary osteodystrophy (AHO) has also not been previ- ously described. Objective: The aim of this study was to identify a GNAS mutation in a patient with a

Steven A. Lietman; James Goldfarb; Nina Desai; Michael A. Levine

93

[Ten years' experience of preimplantation genetic diagnosis in Paris: remaining obstacles and potential solutions].  

PubMed

Preimplantation genetic diagnosis (PGD) has been authorized in France since 1999. Encouraging results have been obtained during the past 10 years in our Paris center, where 832 patients have undergone 1056 IVF-PGD procedures. With the advent of new techniques for the identification of genetic disease markers, our center can now offer PGD procedures for aneuploidy and 75 single-gene diseases. New indications for PGD have also been developed, such as mitochondrial DNA diseases, amyloid neuropathy, pulmonary arterial hypertension, and HLA typing The implantation rate is currently 29,6% and, by 31 December 2009, 151 healthy babies had been born. Unfortunately, demand for PGD procedures far outstrips available technical capacity, and the waiting period is longer than 18 months. Increased funding is urgently needed PMID:22375366

Frydman, René; Achour-Frydman, Nelly; Steffann, Julie; Lamazou, Fredéric; Fanchin, Renato; Burlet, Philippe; Gigarel, Nadine; Romana, Serge; Bonnefont, Jean-Paul; Le Lorch, Marc; Kerbrat, Violaine; Hesters, Laetitia; Munnich, Arnold; Vekemans, Michel

94

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

Microsoft Academic Search

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

Chantal Bouffard; Julie-Kim Godin; Bénédicte Bévière

2010-01-01

95

Multiple aneuploidies in the oocytes of balanced translocation carriers: a preimplantation genetic diagnosis study using first polar body  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) of first polar bod- ies (1PBs) has been used in carriers of balanced chromo- somal reorganizations and also for aneuploidy screening. Although an acceptable number of normal or balanced embryos is usually obtained using PGD in translocation carriers,thepregnancyrateisdisappointinglylow.Todeter- mine whether aneuploidy of chromosomes not involved in the chromosome rearrangements could be the cause of the low

A. Pujol; M. Durban; J. Benet; I. Boiso; J. M. C alafell; J. Egozcue; J. Navarro

2003-01-01

96

Preimplantation genetic diagnosis significantly improves the pregnancy outcome of translocation carriers with a history of recurrent miscarriage and unsuccessful pregnancies  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) for translocations has been shown to significantly reduce the risk of recurrent miscarriage, but because the majority of embryos produced are unbalanced, pregnancy rate is relatively low since 20% or more cycles have no normal or balanced embryos to transfer. The purpose of this study was to evaluate whether PGD could improve pregnancy outcome in translocation

Tetsuo Otani; Muriel Roche; Miho Mizuike; Pere Colls; Tomas Escudero; Santiago Munné

2006-01-01

97

Successful Preimplantation Genetic Diagnosis of Hb Bart's Hydrops Fetalis in Singapore after Fresh and Frozen Embryo Replacement Cycles  

Microsoft Academic Search

Introduction: We report the fi rst successful preimplantation genetic diagnosis (PGD) for Hb Bart's hydrops fetalis in Singapore, involving both fresh and frozen embryo replacement cycles. Clinical Picture: Two couples who were carriers of the Southeast Asian type double gene deletion (-- SEA deletion carriers) requested for PGD. Couple A had 2 previous affected pregnancies, while couple B have a

Christine Yap; Wen Wang; Wei Chin Tan; Mui Nee Lim; Samuel S Chong

98

FISH for pre-implantation genetic diagnosis.  

PubMed

Pre-implantation genetic diagnosis (PGD) is an established alternative to pre-natal diagnosis, and involves selecting pre-implantation embryos from a cohort generated by assisted reproduction technology (ART). This selection may be required because of familial monogenic disease (e.g. cystic fibrosis), or because one partner carries a chromosome rearrangement (e.g. a two-way reciprocal translocation). PGD is available for couples who have had previous affected children, and/or in the case of chromosome rearrangements, recurrent miscarriages, or infertility. Oocytes aspirated following ovarian stimulation are fertilized by in vitro immersion in semen (IVF) or by intracytoplasmic injection of individual spermatocytes (ICSI). Pre-implantation cleavage-stage embryos are biopsied, usually by the removal of a single cell on day 3 post-fertilization, and the biopsied cell is tested to establish the genetic status of the embryo.Fluorescence in situ hybridization (FISH) on the fixed nuclei of biopsied cells with target-specific DNA probes is the technique of choice to detect chromosome imbalance associated with chromosome rearrangements, and to select female embryos in families with X-linked disease for which there is no mutation-specific test. FISH has also been used to screen embryos for sporadic chromosome aneuploidy (also known as PGS or PGD-AS) in order to try and improve the efficiency of assisted reproduction; however, due to the unacceptably low predictive accuracy of this test using FISH, it is not recommended for routine clinical use.This chapter describes the selection of suitable probes for single-cell FISH, assessment of the analytical performance of the test, spreading techniques for blastomere nuclei, and in situ hybridization and signal scoring, applied to PGD in a clinical setting. PMID:20809319

Scriven, Paul N; Ogilvie, Caroline Mackie

2010-01-01

99

FISH for Pre-implantation Genetic Diagnosis  

PubMed Central

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

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

2011-01-01

100

PGD gender selection for non-Mendelian disorders with unequal sex incidence  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) was originally developed for couples whose potential offspring were at risk of severe Mendelian disorders, but has since been extended to other indications. One possible use of PGD is to perform gender selection for couples whose offspring are at increased risk of disorders that do not follow Mendelian inheri- tance, but which are substantially more common

David J. Amor; Carolyn Cameron

2008-01-01

101

Characterization of human PGD blastocysts with unbalanced chromosomal translocations and human embryonic stem cell line derivation  

Microsoft Academic Search

Novel embryonic stem cell lines derived from embryos carrying structural chromosomal abnormalities obtained after preimplantation genetic diagnosis (PGD) are of interest to study in terms of the influence of abnormalities on further development. A total of 22 unbalanced blastocysts obtained after PGD were analysed for structural chromosomal defects. Morphological description and chromosomal status of these blastocysts was established and they

N Frydman; O Féraud; C Bas; M Amit; R Frydman; A Bennaceur-Griscelli; G Tachdjian

2009-01-01

102

6Phosphogluconate dehydrogenase (PGD) genetics in the mouse: Linkage with metabolically related enzyme loci  

Microsoft Academic Search

An electrophoretic polymorphism of 6-phosphogluconate dehydrogenase (PGD) has been observed in the subspecies Mus musculus musculus from northern Denmark. M. m. musculus is interfertile with inbred strains of mice, and F1 hybrids with C57BL\\/6J show a three-banded phenotype. This pattern is consistent with a dimeric enzyme structure with codominant expression of alleles. In backcrosses and the F2 generation, PGD segregated

Verne M. Chapman

1975-01-01

103

[Embryonal genetic diagnosis and reproductive freedom in assisted procreation].  

PubMed

This article analyses the repercussions that the Preimplantational Genetic Diagnosis (PGD) has in the bioethical as well as legal fields in relation with the so-called "reproductive freedom" of the couple. Besides analysing the legal situation of this technique in Spain as well as other surrounding States, the article studies the problems associated with some scenarios of PGD, such as the use in the selection of sex, for therapeutic purposes for third parties, in relation with diseases of a possible late onset, multifactorial or of a variable phenotype expression and for the selection of embryos affected by a disease or disability. All are based on real clinical cases. PMID:17393795

Abellán, Fernando

104

Choosing between possible lives: legal and ethical issues in preimplantation genetic diagnosis.  

PubMed

This article critically appraises the current legal scope of the principal applications of preimplantation genetic diagnosis (PGD). This relatively new technique, which is available to some parents undergoing in vitro fertilization (IVF) treatment, aims to ensure that a child is not born with a seemingly undesirable genetic condition. The question addressed here is whether there should be serious reasons to test for genetic conditions in embryos in order to be able to select between them. The Human Fertilisation and Embryology Authority and the Human Genetics Commission have decided that there should be such reasons by broadly aligning the criteria for PGD with those for selective abortion. This stance is critically explored, as are its implications for the possible use of PGD to select either against or for marginal features or for significant traits. The government is currently reviewing the legal scope and regulation of PGD. PMID:17340769

Scott, Rosamund

2006-01-01

105

Preimplantation genetic diagnosis for monogenic diseases: overview and emerging issues.  

PubMed

Preimplantation genetic diagnosis (PGD) is an established reproductive option for couples at risk of conceiving a pregnancy affected with a known genetic disease, who wish to avoid an (additional) affected child, termination of pregnancy or recurrent miscarriages. Early technologies concentrated on different approaches to direct mutation testing for monogenic diseases using single cell PCR protocols, or sex selection by fluorescent in situ hybridization for X-linked monogenic disease. Development of multiplex fluorescent PCR allowed simultaneously testing of linked markers alongside the mutation test, increasing the accuracy by controlling for contamination and identifying allele drop-out. The advent of highly effective whole genome amplification methods has opened the way for new technologies such as preimplantation genetic haplotyping and microarrays, thus increasing the number of genetic defects that can be detected in preimplantation embryos; the number of cases carried out and the new indications tested increases each year. Different countries have taken very different approaches to legislating and regulating PGD, giving rise to the phenomenon of reproductive tourism. PGD is now being performed for scenarios previously not undertaken using prenatal diagnosis, some of which raise significant ethical concerns. While PGD has benefited many couples aiming to have healthy children, ethical concerns remain over inappropriate use of this technology. PMID:17187482

Renwick, Pamela; Ogilvie, Caroline Mackie

2007-01-01

106

Preimplantation genetic diagnosis: an overview of socio-ethical and legal considerations.  

PubMed

Preimplantation genetic diagnosis (PGD) permits the selection of embryos of a particular genotype prior to implantation. As a reproductive technology involving embryo selection, PGD has become associated with considerable controversy. This review examines some of the ethical, legal, and social issues raised by PGD. Relevant ethical considerations include the status of the embryo and the interests and duties of the parents. On a social policy level, considerations of access as well as the impact of this technology on families, women, and physician's duties also warrant consideration. An analysis of these issues in the context of using PGD for selecting embryos unaffected by a serious disorder and for sex selection is presented. We also present a brief survey of PGD-related regulatory schemes in several countries, including the United Kingdom and the United States. PMID:16724879

Knoppers, Bartha M; Bordet, Sylvie; Isasi, Rosario M

2006-01-01

107

Results of preimplantation genetic diagnosis in patients with Klinefelter's syndrome  

Microsoft Academic Search

With the application of preimplantation genetic diagnosis (PGD), a possible genetic contribution of spermatozoa obtained from 47,XXY non-mosaic Klinefelter patients on preimplantation embryos was analysed in eight couples. Interpretable fluorescence in-situ hybridization results were obtained for 28 out of 33 embryos biopsied (84.8%) and 23 blastomeres were analysed for chromosomes 13, 18, 21, X and Y. Nine out of 23

S Kahraman; N Findikli; H Berkil; E Bakircioglu; E Donmez; S Sertyel; A Biricik

2003-01-01

108

The decision to cancel a preimplantation genetic diagnosis cycle.  

PubMed

It has been suggested that a minimum number (six) of cumulus-oocyte complexes (COCs) should be retrieved for fertilization to offer enough chances to ensure a pregnancy after a preimplantation genetic diagnosis (PGD) procedure. Therefore a decision to cancel a PGD cycle should be adequately weighted to offer the patients the highest chances to obtain a pregnancy. We describe a case where, after retrieving only three COCs suitable for fertilization, a triplet pregnancy was obtained. This case suggests that, although low numbers of COCs can reduce the effectiveness of the PGD procedure, other factors are involved in its final result. Thus, the opportunity of routinely cancelling such cycles should be reconsidered. In addition, this is, to our knowledge, the first case where sex selection was carried out to prevent the birth of carriers of the abnormal gene, and not of affected offspring. PMID:10913955

Santaló, J; Grossmann, M; Giménez, C; Marina, F; Egozcue, J; Marina, S; Vidal, F

2000-07-01

109

Strategies and outcomes of PGD of familial adenomatous polyposis  

Microsoft Academic Search

Owing to adult onset of hereditary cancer, prenatal diagnosis (PND) raises numerous ethical issues on the acceptability to termi- nate an affected pregnancy (TOP). PND for these disorders is often considered as unacceptable by couples as well as geneticists and legal or ethical authorities, but preimplantation genetic diagnosis (PGD), even if subject to controversy, seems to be a more acceptable

C. Moutou; N. Gardes; J.-C. Nicod; S. Viville

2007-01-01

110

Preimplantation genetic diagnosis, an alternative to conventional prenatal diagnosis of the hemoglobinopathies.  

PubMed

Prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) both represent highly important reproductive choices for couples with a high risk of transmitting a severe disease, such as a severe hemoglobinopathy. Conventional PND for hemoglobinopathies based on molecular analysis of trophoblast or amniocyte DNA has been applied for around 30 years, but the major disadvantages with this approach include 'invasive' fetal sampling, and the potential involvement of pregnancy termination when affected. In comparison, the major advantage of PGD over conventional PND is that it supports the initiation of unaffected pregnancies, avoiding the need to terminate affected pregnancies. However, it is a multistep technically demanding procedure requiring the close collaboration of experts from several fields. PGD is also limited by the need to involve assisted reproduction, even in couples without fertility problems. Furthermore, even for fertile couples, pregnancy rates rarely surpass 30-35%. Both PND and PGD have advantages and drawbacks. Before embarking on either procedure, couples should be carefully counseled by experts so that they can select the option most appropriate for them. Finally, whatever their choice, it is paramount that both prenatal and PGD be applied with the highest standards of clinical, laboratory, and ethical practice. PMID:23551498

Traeger-Synodinos, J

2013-04-01

111

Preimplantation genetic diagnosis: development and regulation.  

PubMed

Pre-implantation genetic diagnosis (PGD) is used to biopsy and analyse embryos created through in vitro fertilisation (IVF) to avoid implanting an embryo affected by a mutation or chromosomal abnormality associated with serious illness. It reduces the chance that the parents will be faced with a difficult decision of whether to terminate the pregnancy, if the disorder is detected during the course of gestation. PGD is widely accepted for this purpose although there have been suggestions that such procedures have the effect of de-valuing persons in the community with disabilities. PGD potentially has other more controversial purposes, including the selection of the sex of the baby for personal preferences such as balancing the family, rather than to avoid a sex-linked disorder. Recently PGD has become available to create a donor child who is Human Leukocyte Antigen (HLA) matched with a sibling in need of stem cell transplant. In most cases the intention is to utilise the cord blood. However, an HLA-matched child could potentially be required to be a donor of tissues and organs throughout life. This may arise should the initial cord blood donation fail for any one of several reasons, such as inadequate cord blood cell dose, graft failure after cord blood transplant, or the recipient child experiencing a recurrence of the original illness after transplant. However, such on-going demands could also arise if a HLA-matched child was fortuitously conceived by natural means. As such, the issue is not PGD, but rather whether to harvest bone marrow or a solid organ from a child. This raises the question of whether there should be limits and procedures to protect such children from exploitation until they achieve sufficient competence to be able to make mature and autonomous decisions about whether to donate, even if the consequence may in some cases be that it is too late to save the sibling. Additionally, the parents may not be able to make a dispassionate decision, when they have a conflict of interests between their children. As such, parents may not be the best proxy decision-makers in this area and the decision might be better made by an independent authority or court. This paper considers ethical and legal issues arising from PGD. It will compare the willingness of the HFEA in the United Kingdom to allow this process to be used even in cases where the condition suffered by the sibling is non-heritable, with the more restrictive guidelines in New Zealand and questions the constitutional basis on which ethics committees develop policy in the absence of a legislative framework. PMID:16929812

Thomas, C

2006-06-01

112

Impact of preimplantation genetic diagnosis on IVF outcome in implantation failure patients  

Microsoft Academic Search

Implantation failure (IF) is defined as three or more failed IVF attempts, and preimplantation genetic diagnosis (PGD) is being used in these patients to improve IVF outcome. PGD was performed in 49 implantation failure patients with a mean number of 4.2 ± 1.6 previous IVF failures, and in nine fertile controls. Fluorescence in-situ hybridization (FISH) on blastomeres from biopsied day

T Pehlivan; C Rubio; L Rodrigo; J Romero; J Remohi; C Simón; A Pellicer

2003-01-01

113

[Preimplantation genetic diagnosis--developments to expect?].  

PubMed

Preimplantation genetic diagnosis (PGD) has been practiced for over 20 years. It prevents the birth of children with serious genetic diseases by selecting healthy embryos before pregnancy. In France, the initial indications of PGD have been extended in two directions: on the one hand, to allow identification of a mutation combined with embryo's HLA typing, to obtain, at birth, stem cells for therapeutic purposes, and on the other hand, to avoid transmission of late onset diseases without having to test the at-risk parent. Other applications are practiced worldwide but are not allowed in our country, such as social sexing. Technological developments can enable more complex diagnosis, research of several diseases or other genetic traits. It may be useful, for example, to use this possibility to add screening for Down's syndrome at any PDG in older women, when the risk is high. Other objectives were considered but presenting difficulties in their application, not only for regulatory and technical reasons, but also from an ethical point of view. PMID:23085048

Gosset, P

2012-10-22

114

Preimplantation genetic diagnosis: the ethics of intermediate cases.  

PubMed

According to the current guiding principle regarding preimplantation genetic diagnosis (PGD), the technique should focus on the diagnosis of genetic defects which (may) affect the health of this particular potential child--the so-called 'medical model'. I argue in favour of a more permissive view, also allowing PGD of characteristics which may be relevant for the health of 'third parties'. Two cases are analysed: PGD/HLA typing in order to save a sib, and PGD/sex selection in order to prevent the birth of healthy female carriers of X-linked recessive disorders, who are at high risk of conceiving affected sons. While these cases are at odds with the medical model stricto sensu, they do have a link with health problems. In the first case, the health benefit hoped for is intrafamilial, in the second case the health benefit is transgenerational. These cases illustrate that the traditional dichotomy between the medical model on the one hand and the 'designer' or autonomy model on the other hand is simplistic--they represent an intermediate category. PMID:16123097

de Wert, Guido

2005-08-25

115

Gender Eugenics? The Ethics of PGD for Intersex Conditions.  

PubMed

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

Sparrow, Robert

2013-10-01

116

Ethical considerations on preimplantation genetic diagnosis for HLA typing to match a future child as a donor of haematopoietic stem cells to a sibling  

Microsoft Academic Search

Recently, several requests were made by couples with an affected child who wanted preimplantation genetic diagnosis (PGD) to select embryos in the hope of conceiving an HLA identical donor sibling. This article considers the ethical arguments for and against the application of PGD for this goal. Only embryos HLA matched with an existing sibling in need of a compatible donor

G. Pennings; R. Schots; I. Liebaers

2002-01-01

117

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

Microsoft Academic Search

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

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

2004-01-01

118

New tools for preimplantation genetic diagnosis of Huntington's disease and their clinical applications  

Microsoft Academic Search

Huntington's disease (HD) is a late-onset neurodegenerative disorder transmitted as an autosomal dominant trait. The causative mutation was characterised in 1993. For HD carriers willing to create a family, prenatal diagnosis (PND) or preimplantation genetic diagnosis (PGD) based on the mutation identification can be offered. For at-risk persons who do not want to undergo presymptomatic testing (PT), an exclusion test

Céline Moutou; Nathalie Gardes; Stéphane Viville

2004-01-01

119

Multiplex Nested PCR for Preimplantation Genetic Diagnosis of Spinal Muscular Atrophy  

Microsoft Academic Search

Objective: Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder caused in most patients by homozygous deletion of the SMN1 gene. For a carrier couple at a 25% risk of affected offspring, preimplantation genetic diagnosis (PGD) offers an alternative to prenatal diagnosis and termination of affected pregnancies. Our objective was to develop an accurate and reliable single-cell multiplex

Mira Malcov; Tamar Schwartz; Nava Mei-Raz; Dalit Ben Yosef; Ami Amit; Joseph B. Lessing; Ruth Shomrat; Avi Orr-Urtreger; Yuval Yaron

2004-01-01

120

A retrospective study of paediatric health and development following pre-implantation genetic diagnosis and screening  

Microsoft Academic Search

Pre-implantation genetic diagnosis and screening (PGD and PGS) are treatments for patients that have (or are carriers of) an inherited genetic disorder, or who have had a history of miscarriage, problems with embryo implantation, etc. Often conducted alongside assisted reproductive technologies (ART), a number of embryos are produced, and the DNA and chromosomes of each are tested for various disorders

Mark Olive; Alison Lashwood; Tony Solomonides

2011-01-01

121

Results on single cell PCR for Huntington's gene and WAVE™ product analysis for preimplantation genetic diagnosis  

Microsoft Academic Search

Triple repeat base pair amplification is the basis for a number of prevalent genetic diseases such as Huntington's, Fragile X, Myotonic Dystrophy and others. We have chosen to investigate the use of PCR to amplify a portion of the Huntington's gene in single cells in order to develop a clinical test system for preimplantation genetic diagnosis (PGD). Amplification of CAG

Kenneth C Drury; M. C Liu; S Lilleberg; S Kipersztok; R. S Williams

2001-01-01

122

The Case for a Parental Duty to Use Preimplantation Genetic Diagnosis for Medical Benefit  

Microsoft Academic Search

This article explores the possibility that there is a parental duty to use preimplantation genetic diagnosis (PGD) for the medical benefit of future children. Using one genetic disorder as a paradigmatic example, we find that such a duty can be supported in some situations on both ethical and legal grounds. Our analysis shows that an ethical case in favor of

Janet Malek; Judith Daar

2012-01-01

123

Reduced allele dropout in single-cell analysis for preimplantation genetic diagnosis of cystic fibrosis  

Microsoft Academic Search

Background: For couples at risk of transmitting a known single-gene defect, preimplantation genetic diagnosis (PGD) allows the identification and transfer of only unaffected embryos followingin vitro fertilisation (IVF), single-cell biopsy at about the eight-cell stage, and genetic analysis by PCR. This technique therefore avoids the risk of terminating an affected pregnancy diagnosed later in gestation.

PIERRE F. RAYj; Robert M. L. Winston; Alan H. Handyside

1996-01-01

124

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

Microsoft Academic Search

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

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

2011-01-01

125

Sex selection and preimplantation genetic diagnosis at The Farah Hospital.  

PubMed

The issue of sex selection by using preimplantation genetic diagnosis (PGD) for non-medical reasons has been the subject of heated debate. Although the ethical arguments regarding this subject are complex, we would like to extend and express some views based on practical experience, with a special focus on individual needs in developing countries, taking into consideration: social, cultural, religious, financial and scientific aspects. PMID:12470356

Kilani, Z; Haj Hassan, L

126

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

Microsoft Academic Search

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

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

2009-01-01

127

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

128

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

Microsoft Academic Search

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

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

129

Polymorphism at the G6pd and 6Pgd loci in Drosophila melanogaster . IV. Genetic factors modifying enzyme activity  

Microsoft Academic Search

Different homozygous lines of similar genotype with respect to G6pd and 6Pgd were shown to have different enzyme activities for G6PD and 6PGD. Crosses between high and low lines suggested that there were modifying genes present on the autosomes, while others were probably located on the X chromosome. Allelic variation within each electrophoretic class of G6pd and 6Pgd might, however,

R. Bijlsmal

1980-01-01

130

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

Microsoft Academic Search

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

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

2007-01-01

131

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

PubMed Central

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

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

2013-01-01

132

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

PubMed

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

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

2013-09-05

133

Moral attitudes and beliefs among couples pursuing PGD for sex selection  

Microsoft Academic Search

This article reports the results from a study of couples participating in a research protocol in which IVF\\/preimplantation genetic diagnosis (PGD) was available for non-medical sex selection. The study sought to characterize the moral attitudes and beliefs of couples actively pursuing IVF\\/PGD solely for purposes related to sex selection. Eighteen couples participated in ethnographic interviews from November 2005 to April

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

2010-01-01

134

PGD for all cystic fibrosis carrier couples: novel strategy for preventive medicine and cost analysis  

Microsoft Academic Search

Over 1000 children affected with cystic fibrosis (CF) are born annually in the USA. Since IVF with preimplantation genetic diagnosis (PGD) is an alternative to raising a sick child or to aborting an affected fetus, a cost–benefit analysis was performed for a national IVF–PGD program for preventing CF. The amount spent to deliver healthy children for all CF carrier-couples by

I. Tur-Kaspa; G. Aljadeff; S. Rechitsky; H. E. Grotjan; Y. Verlinsky

2010-01-01

135

The use of preimplantation genetic diagnosis in sex selection for family balancing in India  

Microsoft Academic Search

This paper describes the use of preimplantation genetic diagnosis (PGD) in sexing embryos for family balancing in a private IVF clinic in India from April 1999 to April 2001. Embryos were biopsied and analysed on day 3, cultured in sequential media and then transferred on day 4 or day 5 after morphological selection of the best embryos. From a total

A Malpani; D Modi

2002-01-01

136

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

Microsoft Academic Search

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

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

137

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

Microsoft Academic Search

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

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

2002-01-01

138

Polar Body-Based Preimplantation Genetic Diagnosis for N-Acetylglutamate Synthase Deficiency  

Microsoft Academic Search

Objective: We describe a sensitive and highly reliable preimplantation genetic diagnosis (PGD) assay for N-acetylglutamate synthetase (NAGS) deficiency using polar body (PB) analysis in conjunction with multiple markers flanking the gene. This rare autosomal recessive mitochondrial disorder is characterized by hyperammonemia, uncontrollable movements, developmental delay, visual impairment, failure to thrive and vomiting and is caused by mutations in the NAGS

G. Altarescu; B. Brooks; T. Eldar-Geva; E. J. Margalioth; A. Singer; E. Levy-Lahad; P. Renbaum

2008-01-01

139

Clinical aspects of preimplantation genetic diagnosis for single gene disorders combined with HLA typing  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) for single gene disorders combined with human leukocyte antigen (HLA) matching has recently emerged as a therapeutic tool for stem cell transplantation in couples bearing an affected offspring. There may exist, however, several patient- or cycle-specific limitations for certain couples. This article documents data regarding experience of single gene disorders combined with HLA matching obtained at

S Kahraman; G Karlikaya; S Sertyel; H Karadayi; N Findikli

2004-01-01

140

Will preimplantation genetic diagnosis assist patients with a poor prognosis to achieve pregnancy?  

Microsoft Academic Search

ductive techniques may be related to the high rates of chromo- somal disorders which are routinely observed in oocytes 3 To whom correspondence should be addressed obtained from stimulated cycles or during early cleavage events PGD (preimplantation genetic diagnosis) of aneuploidy for (Plachot and Mandelbaum, 1990; Pellestor, 1991; Delhanty and chromosomes X, Y, 13, 18 and 21 was carried out

L. Gianaroli; M. C. Magli; S. Munne; A. Fiorentino; N. Montanaro; A. P. Ferraretti

1997-01-01

141

Analysis of chromosome segregation during preimplantation genetic diagnosis in both male and female translocation heterozygotes  

Microsoft Academic Search

Individuals carrying translocations suffer from reduced fertility or spontaneous abortions and seek help in form of assisted reproductive technology (ART) and preimplantation genetic diagnosis (PGD). While most translocations are relatively easy to detect in metaphase cells, the majority of embryonic cells biopsied in the course of in vitro fertilization (IVF) procedures are in interphase. These nuclei are thus unsuitable for

S. Munné

2005-01-01

142

Blastomere fixation techniques and risk of misdiagnosis for preimplantation genetic diagnosis of aneuploidy  

Microsoft Academic Search

One of the most critical steps in preimplantation genetic diagnosis (PGD) studies is the fixation required to obtain good fluorescence in-situ hybridization (FISH) nuclear quality without losing any of the cells analysed. Different fixation techniques have been described. The aim of this study was to compare three fixation methods (1, acetic acid\\/methanol; 2, Tween 20; 3, Tween 20 and acetic

Esther Velilla; Tomas Escudero; Santiago Munné

2002-01-01

143

Preimplantation diagnosis for immunodeficiencies  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) has become an established procedure for the detection of single gene disorders, and has recently been performed together with human leukocyte antigen (HLA) typing for couples with children affected by genetic disorders that require HLA-identical stem cell transplantation therapy. For these couples, PGD can ensure the birth of an unaffected child, and because HLA-matched stem cell

Yury Verlinsky; Svetlana Rechitsky; Tatyana Sharapova; Katya Laziuk; Irina Barsky; Oleg Verlinsky; Ilan Tur-Kaspa; Anver Kuliev

2007-01-01

144

A clinical perspective on ethical arguments around prenatal diagnosis and preimplantation genetic diagnosis for later onset inherited cancer predispositions  

Microsoft Academic Search

Prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) for later onset and\\/or reduced penetrance inherited cancer\\u000a predispositions, e.g. familial adenomatous polyposis, hereditary non-polyposis colorectal cancer\\/Lynch syndrome and hereditary\\u000a breast and ovarian cancer, raise a number of ethical issues. Some of these are the same as for conditions which present early\\u000a in childhood, are fully penetrant and for which no\\/limited treatment

Tara Clancy

2010-01-01

145

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

Microsoft Academic Search

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

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

2003-01-01

146

Preimplantation Diagnosis of Thalassemias  

Microsoft Academic Search

Purpose:Preimplantation genetic diagnosis (PGD) is an important option for couples at risk of having children with ß-globin mutations to avoid selective abortions of affected fetuses following prenatal diagnosis.

A. Kuliev; S. Rechitsky; O. Verlinsky; V. Ivakhnenko; S. Evsikov; G. Wolf; M. Angastiniotis; D. Georghiou; V. Kukharenko; C. Strom; Y. Verlinsky

1998-01-01

147

More than 10 years after the first 'savior siblings': parental experiences surrounding preimplantation genetic diagnosis.  

PubMed

Preimplantation genetic diagnosis (PGD) to create a healthy donor for a sibling's hematopoetic stem cell transplantation for a child with Fanconi Anemia (FA) was first reported in 2001. Yet we know little about the experiences of parents who have encountered decision making surrounding PGD and human leukocyte antigen (HLA)-typing. The first aim of this study was to understand parents' awareness, perceptions and beliefs about reproductive decision-making including emotional, cognitive, moral dimensions as well as regret surrounding the use of this technology. The second aim was to describe the experiences and rationale of parents of children with a single gene disorder regarding the factors that influenced their decision making surrounding the use of natural pregnancy and/or PGD and HLA-typing. Parents from two national FA support networks in the US and Canada responded to an emailed survey about reproductive decision making and outcomes surrounding natural pregnancy and PGD and HLA-typing. Descriptive statistics and Pearson's Chi-Square tests were used to describe and compare data. Our results indicate that the most important factors in the PGD decision making process were the health of the child and cognitive appraisals followed by emotional responses and then moral judgments. A significant difference was noted in parents considering natural pregnancy before and after 2001 (p?=?0.01). Unexpected findings were that less than 35 % of parents were offered PGD by any health care professional and only 70 % were aware PGD with HLA-typing was a reproductive option. Our research suggests that the option of PGD and HLA-typing may influence parents' reproductive decision making choices. PMID:23624741

Zierhut, Heather; Macmillan, Margaret L; Wagner, John E; Bartels, Dianne M

2013-04-28

148

Pregnancy after preimplantation genetic diagnosis for Ataxia Telangiectasia.  

PubMed

Ataxia Telangiectasia (AT) is an autosomal recessive disorder with an incidence estimated at 1 in 40 000 to 1 in 100 000 live births. More than 100 different somatic and germ-line mutations have been identified in the AT gene, the majority of which cause premature protein truncation. The immense size of the AT gene (66 exons) complicates the detection of mutations. A Saudi family with three affected children suffering from AT consulted our IVF centre for preimplantation genetic diagnosis (PGD). Despite advanced maternal age and unknown mutation, the family was screened for AT mutations. A large deletion in the gene was found to be responsible for the phenotype of AT. The mutation detection permitted us to perform PGD on AT for the first time. Single cell PCR consisted of amplifying one of the deleted exons, exon 19. Homozygous affected embryos show an absence of the exon, while in heterozygous or normal embryos the exon is amplified successfully. After ICSI, three embryos were suitable for embryo biopsy. After biopsy only one embryo showed exon amplification and was transferred. A singleton pregnancy ensued and prenatal diagnosis confirmed the presence of exon 19. This report demonstrates that PGD is feasible despite advanced maternal age and poor response to follicle stimulation. PMID:12149412

Hellani, Ali; Laugé, Anthony; Ozand, Pinard; Jaroudi, Kamal; Coskun, Serdar

2002-08-01

149

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.

Theodosiou, Anastasia A.; Johnson, Martin H.

2011-01-01

150

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

PubMed

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

2011-01-24

151

ESHRE PGD Consortium data collection IV: May-December 2001.  

PubMed

The ESHRE PGD Consortium was formed in 1997 to survey the practice of preimplantation genetic diagnosis (PGD). Since then, three reports have been published giving an overview on PGD from an ever-increasing number of centres and reporting on an increasing number of PGD cycles and pregnancies and babies born after PGD. After these initial influential publications, important shortcomings were identified primarily on the method of data collection, i.e. with Excel spreadsheets, and in the timing of the collection (cycles were collected in a different time frame from pregnancies and babies, making the follow-up of cycles very difficult). This is why the Steering Committee has made a major investment in developing and implementing a new database in FileMaker Pro 6. It was also decided that cycles would be collected from one calendar year, as well as the pregnancies and babies ensuing from that particular calendar year. This gave us the opportunity to take a closer look at the data collected earlier, and to attempt to improve their quality. This is a report on the corrected data from the first three data collections (I-III) as well as the result of the last data collection (IV) that was completely carried out using the new database. PMID:15550497

Sermon, K; Moutou, C; Harper, J; Geraedts, J; Scriven, P; Wilton, L; Magli, M C; Michiels, A; Viville, S; De Die, C

2004-11-18

152

An update of preimplantation genetic diagnosis in gene diseases, chromosomal translocation, and aneuploidy screening  

PubMed Central

Preimplantation genetic diagnosis (PGD) is gradually widely used in prevention of gene diseases and chromosomal abnormalities. Much improvement has been achieved in biopsy technique and molecular diagnosis. Blastocyst biopsy can increase diagnostic accuracy and reduce allele dropout. It is cost-effective and currently plays an important role. Whole genome amplification permits subsequent individual detection of multiple gene loci and screening all 23 pairs of chromosomes. For PGD of chromosomal translocation, fluorescence in-situ hybridization (FISH) is traditionally used, but with technical difficulty. Array comparative genomic hybridization (CGH) can detect translocation and 23 pairs of chromosomes that may replace FISH. Single nucleotide polymorphisms array with haplotyping can further distinguish between normal chromosomes and balanced translocation. PGD may shorten time to conceive and reduce miscarriage for patients with chromosomal translocation. PGD has a potential value for mitochondrial diseases. Preimplantation genetic haplotyping has been applied for unknown mutation sites of single gene disease. Preimplantation genetic screening (PGS) using limited FISH probes in the cleavage-stage embryo did not increase live birth rates for patients with advanced maternal age, unexplained recurrent abortions, and repeated implantation failure. Polar body and blastocyst biopsy may circumvent the problem of mosaicism. PGS using blastocyst biopsy and array CGH is encouraging and merit further studies. Cryopreservation of biopsied blastocysts instead of fresh transfer permits sufficient time for transportation and genetic analysis. Cryopreservation of embryos may avoid ovarian hyperstimulation syndrome and possible suboptimal endometrium.

Chang, Li-Jung; Chen, Shee-Uan; Tsai, Yi-Yi; Hung, Chia-Cheng; Fang, Mei-Ya

2011-01-01

153

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

PubMed

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

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

2007-07-01

154

Simplified PGD of common determinants of haemoglobin Bart’s hydrops fetalis syndrome using multiplex-microsatellite PCR  

Microsoft Academic Search

The high incidence of double-gene deletions in ?-thalassaemia increases the risk of having pregnancies with homozygous ?0-thalassaemia, the cause of the lethal haemoglobin (Hb) Bart’s hydrops fetalis syndrome. Preimplantation genetic diagnosis (PGD) has played an important role in preventing such cases. However, the current gap-PCR based PGD protocol for deletional ?-thalassaemia requires specific primer design for each specific deletion. A

Wen Wang; Christine H. A. Yap; Seong Feei Loh; Arnold S. C. Tan; Mui Nee Lim; Ethiraj B. Prasath; Melinda L. H. Chan; Wei Chin Tan; Boran Jiang; Gare Hoon Yeo; Joyce Mathew; Angela Ho; Sherry S. Y. Ho; Peng Cheang Wong; Mahesh A. Choolani; Samuel S. Chong

2010-01-01

155

Novel One-Step Multiplex PCR-Based Method for HLA Typing and Preimplantational Genetic Diagnosis of ?-Thalassemia  

PubMed Central

Preimplantation genetic diagnosis (PGD) of single gene disorders, combined with HLA matching (PGD-HLA), has emerged as a tool for couples at risk of transmitting a genetic disease to select unaffected embryos of an HLA tissue type compatible with that of an existing affected child. Here, we present a novel one-step multiplex PCR to genotype a spectrum of STRs to simultaneously perform HLA typing and PGD for ?-thalassemia. This method is being routinely used for PGD-HLA cycles in our department, with a genotyping success rate of 100%. As an example, we present the first successful PGD-HLA typing in Spain, which resulted in the birth of a boy and subsequent successful HSC transplantation to his affected brother, who is doing well 4 years following transplantation. The advantage of our method is that it involves only a round of single PCR for multiple markers amplification (up to 10 markers within the HLA and 6 markers at the ?-globin loci). This strategy has allowed us to considerably reduce the optimization of the PCR method for each specific PGD-HLA family as well as the time to obtain molecular results in each cycle.

Fernandez, Raquel M.; Pecina, Ana; Lozano-Arana, Maria Dolores; Garcia-Lozano, Juan Carlos; Borrego, Salud; Antinolo, Guillermo

2013-01-01

156

Novel one-step multiplex PCR-based method for HLA typing and preimplantational genetic diagnosis of ?-Thalassemia.  

PubMed

Preimplantation genetic diagnosis (PGD) of single gene disorders, combined with HLA matching (PGD-HLA), has emerged as a tool for couples at risk of transmitting a genetic disease to select unaffected embryos of an HLA tissue type compatible with that of an existing affected child. Here, we present a novel one-step multiplex PCR to genotype a spectrum of STRs to simultaneously perform HLA typing and PGD for ?-thalassemia. This method is being routinely used for PGD-HLA cycles in our department, with a genotyping success rate of 100%. As an example, we present the first successful PGD-HLA typing in Spain, which resulted in the birth of a boy and subsequent successful HSC transplantation to his affected brother, who is doing well 4 years following transplantation. The advantage of our method is that it involves only a round of single PCR for multiple markers amplification (up to 10 markers within the HLA and 6 markers at the ?-globin loci). This strategy has allowed us to considerably reduce the optimization of the PCR method for each specific PGD-HLA family as well as the time to obtain molecular results in each cycle. PMID:23710452

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

2013-04-04

157

Derivation of new human embryonic stem cell lines from preimplantation genetic screening and diagnosis-analyzed embryos  

Microsoft Academic Search

In this study, we focused on the derivation of human embryonic stem cell (hESC) from preimplantation genetic screening (PGS)-analyzed\\u000a and preimplantation genetic diagnosis (PGD)-analyzed embryos. Out of 62 fresh PGD\\/PGS-analyzed embryos, 22 embryos reached\\u000a the blastocyst stage. From 12 outgrowth blastocysts, we derived four hESC lines onto a feeder layer. Surprisingly, karyotype\\u000a analysis showed that hESC lines derived from aneuploid

Adeleh Taei; Hamid Gourabi; Ali Seifinejad; Mehdi Totonchi; Ebrahim Shahbazi; Mojtaba Rezazadeh Valojerdi; Poopak Eftekhari; Leila Karimian; Hossein Baharvand

2010-01-01

158

Preimplantation genetic diagnosis for neurofibromatosis type 1  

Microsoft Academic Search

PGD is an alternative to prenatal diagnosis that circumvents therapeutic abortion. Diagnosis is carried out on single cells obtained from three-day-old embryos, and only those that are free of the disease under consideration are transferred to the mother. Neurofibromatosis type 1 (NF1) is a common neurocutaneous disorder, inherited as an autosomal dominant trait and caused by mutations in the NF1

C. Spits; M. De Rycke; N. Van Ranst; H. Joris; W. Verpoest; W. Lissens; P. Devroey; A. Van Steirteghem; I. Liebaers; K. Sermon

2005-01-01

159

Controlling misdiagnosis errors in preimplantation genetic diagnosis: a comprehensive model encompassing extrinsic and intrinsic sources of error  

Microsoft Academic Search

We have developed a mathematical model to explore accuracy of preimplantation genetic diagnosis (PGD) using single cell polymerase chain reaction (PCR). The model encompasses both extrinsic technical errors and intrinsic errors related to nuclear and chromosomal abnormalities. Using estimates for these errors, we have calculated the probability of a serious error (affected embryo diagnosed as unaffected) using a variety of

C. M. Lewis; T. Pinel; J. C. Whittaker; A. H. Handyside

2001-01-01

160

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

161

Successful Hematopoietic Stem Cell Transplantation for Fanconi Anemia from an Unaffected HLA Genotypically Identical Sibling Selected Using Preimplantation Genetic Diagnosis  

Microsoft Academic Search

The only proven cure for Fanconi anemia (FA)-associated bone marrow failure is successful allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT with donors other than HLA-identi- cal siblings is associated with high mor- bidity and poor survival. Therefore, we used preimplantation genetic diagnosis (PGD) to select an embryo produced by in vitro fertilization (IVF) that was unaffected by FA and

Jeffrey P Kahn; Margaret L MacMillan; Norma KC Ramsay; John E Wagner

2003-01-01

162

Preimplantation genetic diagnosis for ?-thalassaemia using sequencing of single cell PCR products to detect mutations and polymorphic loci  

Microsoft Academic Search

In order to carry out preimplantation genetic diagnosis (PGD) for ?-thalassaemia, we have applied direct sequencing of single cell PCR products to detect mutations and polymorphic loci within the ?-globin gene. Conventional duplex PCR was used to amplify two regions of the ?-globin gene with an amplification efficiency of 79% for blastomeres. Sequencing data were obtained for 100% of amplified

Nicole D. Hussey; Tenielle Davis; Jenny R. Hall; Michael F. Barry; Rogan Draper; Robert J. Norman; Zbigniew Rudzki

2002-01-01

163

Development and clinical application of a strategy for preimplantation genetic diagnosis of single gene disorders combined with HLA matching  

Microsoft Academic Search

Preimplantation HLA matching has recently emerged as a tool for couples desiring to conceive a potential donor progeny for transplantation in a sibling with a life-threatening disorder. In this paper we describe a strategy optimized for preimplantation genetic diagnosis (PGD) of haemoglobinopathies combined with HLA matching. This procedure involves a minisequencing- based genotyping of HLA regions A, B, C and

F. Fiorentino; A. Biricik; H. Karadayi; H. Berkil; G. Karlikaya; S. Sertyel; D. Podini; M. Baldi; M. C. Magli; L. Gianaroli; S. Kahraman

2004-01-01

164

The case for a parental duty to use preimplantation genetic diagnosis for medical benefit.  

PubMed

This article explores the possibility that there is a parental duty to use preimplantation genetic diagnosis (PGD) for the medical benefit of future children. Using one genetic disorder as a paradigmatic example, we find that such a duty can be supported in some situations on both ethical and legal grounds. Our analysis shows that an ethical case in favor of this position can be made when potential parents are aware that a possible future child is at substantial risk of inheriting a serious genetic condition. We further argue that a legal case for a duty to use PGD for medical benefit can be made in situations in which potential parents have chosen to conceive through in vitro fertilization and know that any children conceived are at substantial risk of having a serious genetic condition. PMID:22452463

Malek, Janet; Daar, Judith

2012-01-01

165

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.

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

2012-01-01

166

PGD of ?-thalassaemia and HLA haplotypes using OmniPlex whole genome amplification  

Microsoft Academic Search

A strategy was developed using the OmniPlex technology of whole genome amplification for preimplantation genetic diagnosis (PGD) of single gene diseases and human leukocyte antigen (HLA) haplotypes. The amplified genomic DNA library was subsequently examined separately for mutation analysis with mini-sequence and for short tandem repeat (STR) markers within the HLA loci. To evaluate the reliability of the protocol prior

Shee-Uan Chen; Yi-Ning Su; Mei-Ya Fang; Li-Jung Chang; Yi-Yi Tsai; Li-Ting Lin; Chien-Nan Lee; Yu-Shih Yang

2008-01-01

167

Effect of PGD on implantation and ongoing pregnancy rates in cases with predominantly macrocephalic spermatozoa  

Microsoft Academic Search

Although its occurrence is rare, the presence of large headed or macrocephalic spermatozoa and increased chromosomal abnormality has recently been reported by several groups. Moreover, when intracytoplasmic sperm injection (ICSI) was performed with samples containing macrocephalic spermatozoa, lower fertilization and implantation rates result in poor clinical outcome. In order to evaluate the impact of preimplantation genetic diagnosis (PGD) on implantation

S Kahraman; S Sertyel; N Findikli; Y Kumtepe; N Oncu; S Melil; S Unal; H Yelke; P Vanderzwalmen

2004-01-01

168

Which patients with recurrent implantation failure after IVF benefit from PGD for aneuploidy screening?  

Microsoft Academic Search

Patients with recurrent IVF failure are defined as patients who are younger than 37 years and who had at least three consecutive unsuccessful IVF\\/intracytoplasmic sperm injection (ICSI) cycles with good quality embryos. These patients might be predisposed to chromosome errors in their embryos and therefore might benefit from preimplantation genetic diagnosis for aneuploidy screening (PGD-AS). This technique is, however, expensive

P Platteau; C Staessen; A Michiels; A Van Steirteghem; I Liebaers; P Devroey

2006-01-01

169

Micromanipulation of cryopreserved embryos and cryopreservation of micromanipulated embryos in PGD  

Microsoft Academic Search

The possibility to employ cryopreservation in Preimplantation Genetic Diagnosis (PGD) should enlarge the opportunities for research and clinical activity. For these purposes, we tried three kinds of approaches on human abnormal embryos: (1) cryopreservation of biopsied embryos; (2) biopsy of thawed embryos; and (3) biopsy of embryos derived from thawed oocytes. Our preliminary results show that: (1) biopsy of thawed

P. M. Ciotti; C. Lagalla; A. S. Ricco; R. Fabbri; A. Forabosco; E. Porcu

2000-01-01

170

Rapid and powerful decaplex and dodecaplex PGD protocols for Duchenne muscular dystrophy  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD) is a common childhood lethal X-linked recessive disorder, resulting from deletions, duplications and point mutations in the dystrophin gene. Single-cell protocols for preimplantation genetic diagnosis (PGD) still remain challenging due to the enormous size of the gene and the high risk of intragenic recombination, limitations that often lead to sex determination and selection of female embryos.

A Girardet; C Fernandez; M Claustres

2009-01-01

171

Perinatal genetics: Diagnosis and treatment  

SciTech Connect

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

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

1986-01-01

172

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

Microsoft Academic Search

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

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

2003-01-01

173

Preimplantation genetic diagnosis of spinocerebellar ataxia 3 by (CAG)n repeat detection  

Microsoft Academic Search

Spinocerebellar ataxia 3 (SCA3) is an autosomal dominant neurodegenerative disorder characterized by variable expression and a variable age of onset. SCA3\\/MJD (Machado-Joseph disease) is caused by an expansion of a (CAG)n repeat in the MJD1 gene on chromosome 14q32.1. A single cell PCR protocol has been developed for preimplantation genetic diagnosis (PGD) of SCA3 to select unaffected embryos on the

M. Drusedau; J. C. F. M. Dreesen; C. de Die-Smulders; K. Hardy; M. Bras; J. C. M. Dumoulin; J. L. H. Evers; H. J. M. Smeets; J. P. M. Geraedts; J. Herbergs

2004-01-01

174

Identification of embryonic chromosomal abnormality using FISH-based preimplantaion genetic diagnosis  

Microsoft Academic Search

Objective: Embryonic chromosomal abnormality is one of the main reasons for in vitro fertilization (IVF) failure. This study\\u000a aimed at evaluating the value of Fluorescence in-situ Hybridization (FISH)-based Preimplantation Genetic Diagnosis (PGD) in\\u000a screening for embryonic chromosomal abnormality to increase the successful rate of IVF. Method: Ten couples, four with high\\u000a risk of chromosomal abnormality and six infertile couples, underwent

Ying-hui Ye; Chen-ming Xu; Fan Jin; Yu-li Qian

2004-01-01

175

Pregnancy following intracytoplasmic sperm injection and preimplantation genetic diagnosis after the conservative management of endometrial cancer  

Microsoft Academic Search

A rare case of a patient with conservatively treated endometrial carcinoma who conceived and delivered a healthy baby after the transfer of embryos with intracytoplasmic sperm injection (ICSI) and preimplantation genetic diagnosis (PGD) is presented. A 41-year-old woman had an office hysteroscopy in the infertility work-up and stage I endometrial adenocarcinoma was diagnosed. After conservative treatment, the patient underwent ICSI

A Demirol; M Bahce; A Ayhan; T Gurgan

2005-01-01

176

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

PubMed

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

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

2010-09-26

177

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

PubMed Central

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

Hershberger, Patricia E.; Pierce, Penny F.

2009-01-01

178

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

PubMed Central

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

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

2012-01-01

179

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

PubMed

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

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

2012-12-26

180

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

PubMed

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

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

2011-09-22

181

Preimplantation genetic diagnosis, reproductive freedom, and deliberative democracy.  

PubMed

In this paper I argue that the account of deliberative democracy advanced by Amy Gutmann and Dennis Thompson (1996, 2004) is a useful normative theory that can help enhance our deliberations about public policy in morally pluralistic societies. More specifically, I illustrate how the prescriptions of deliberative democracy can be applied to the issue of regulating non-medical uses of pre-implantation genetic diagnosis (PGD), such as gender selection. Deliberative democracy does not aim to win a philosophical debate among rival first-order theories, such as libertarianism, egalitarianism or feminism. Rather, it advances a second-order analysis that strives to help us determine what would constitute a reasonable balance between the conflicting fundamental values that arise in the context of regulating PGD. I outline a theoretical model (called the Reasonable Genetic Intervention Model) that brings these issues to the fore. Such a model incorporates the concern for both procedural and substantive principles; and it does so in way that takes provisionality seriously. PMID:19251775

Farrelly, Colin

2009-02-27

182

Preimplantation genetic diagnosis: understanding what parents plan to tell their children about their conception.  

PubMed

Over 10,000 babies have been born by PGD and PGS worldwide (Simpson, Prenatal Diagnosis 30(7): 682-695 2010). The experience of parents who have undergone this procedure and their children's well-being are documented, but no research to date has explored whether parents intend to tell their children how they were conceived and whether this raises special issues for them. PGD practitioners recommend research in this area as parents of children born by PGD increasingly ask questions pertaining to disclosure. We conducted 30 in-depth interviews with couples who have had a baby conceived by PGD. We explored what couples plan to tell their children about how they were conceived, when they plan to do this, and issues they anticipate may arise. The couples had a family history of a monogenic disorder or chromosome rearrangement. Six themes emerged which highlight key issues: (1) To tell or not to tell? (2) Primary reason for undergoing PGD, (3) The ideal time to tell, (4) Situations which may warrant earlier disclosure, (5) Words which parents might choose, and (6) Issues which parents anticipate may arise. We conclude that parents are likely to inform their children about PGD because there is an affected sibling or relative about whom they ask questions, and/or their children are carriers of a condition their parents feel obliged to tell them about. Parents felt they would benefit from access to a genetic counsellor at the time of disclosure and are optimistic about the future of reproductive technology for their children. PMID:23613153

Kosicka-Slawinska, Monika; Clarke, Angus; Lashwood, Alison

2013-04-24

183

ESHRE PGD Consortium data collection V: cycles from January to December 2002 with pregnancy follow-up to October 2003.  

PubMed

The fifth report of the ESHRE PGD Consortium is presented (data collection V). For the first time, the cycle data were collected for one calendar year (2002) in the following October, so that data collection was complete for pregnancies and babies. The data were collected using a Filemaker Pro database and divided into referrals, cycles, pregnancies and babies. There are currently 66 active centres registered with the consortium; however, the data presented here were obtained from 43 centres and included 1603 referrals, 2219 cycles, 485 pregnancies and 382 babies born. The cycle data were divided into preimplantation genetic diagnosis (PGD) for inherited disorders (including chromosome abnormalities, sexing for X-linked disease and monogenic disorders), aneuploidy screening (PGS) and the use of PGD for social sexing. Data collection V is compared with the previous cumulative data collection (I-IV), which comprised 4058 PGD/PGS cycles that reached oocyte retrieval. PMID:16172150

Harper, J C; Boelaert, K; Geraedts, J; Harton, G; Kearns, W G; Moutou, C; Muntjewerff, N; Repping, S; SenGupta, S; Scriven, P N; Traeger-Synodinos, J; Vesela, K; Wilton, L; Sermon, K D

2005-09-19

184

Averting abnormal inheritance: potential of gene therapy and preimplantation diagnosis  

Microsoft Academic Search

Serious inherited disease in children can be averted by preimplantation genetic diagnosis (PGD) and potentially by gene therapy in addition to prenatal diagnosis. PGD is now well established and provides a secure, if expensive and complex form of care. Gene therapy has been practised only in animals, although its success in alleviating various conditions in adults and newborns, together with

Adrian J. Thrasher; Robert G Edward

2004-01-01

185

Preimplantation genetic diagnosis of ?-thalassemia using real-time polymerase chain reaction with fluorescence resonance energy transfer hybridization probes  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) is employed increasingly to allow transfer of embryos to the uterus in assisted reproduction procedures. There are three stages of biopsy: polar bodies, one or two blastomeres from the cleavage-stage embryos, and trophectoderm cells (?5cells) from the blastocyst-stage embryos. Validation of polymerase chain reaction (PCR)-based assays are challenging because only limited genetic material can be obtained

Chia-Cheng Hung; Shee-Uan Chen; Shin-Yu Lin; Mei-Ya Fang; Li-Jung Chang; Yi-Yi Tsai; Li-Ting Lin; Yu-Shih Yang; Chien-Nan Lee; Yi-Ning Su

2010-01-01

186

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

PubMed

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

Roberts, Jason C

2002-07-23

187

Pregnancy after preimplantation genetic diagnosis for Sanjad-Sakati syndrome.  

PubMed

Sanjad-Sakati syndrome (SSS) is an autosomal recessive disorder characterized by congenital hypoparathyroidism, growth and mental retardation. In Saudi Arabia, the disease is caused by a deletion of 12 bp (155-166nt) in the tubulin-specific chaperone E gene. In a family with two affected siblings with SSS, preimplantation genetic diagnosis (PGD) was performed. Fluorescent PCR (F-PCR) was utilized to check the heterozygosity and the homozygosity status of the parents and the affected children, respectively. F-PCR was then optimized for single-cell analysis by using peripheral blood lymphocytes. The patient underwent a cycle with intra-cytoplasmic sperm injection. A total of 11 embryos were obtained and biopsied. There were five heterozygous, three homozygous affected and three normal embryos. One heterozygous and one normal embryo were transferred because of their very good quality (morula). A singleton pregnancy was obtained, and amniosynthesis confirmed the presence of the heterozygous fetus. These results show for the first time, the feasibility of PGD for SSS. PMID:15065107

Hellani, Ali; Aqueel, Aida; Jaroudi, Kamal; Ozand, Pinar; Coskun, Serdar

2004-04-01

188

Preimplantation genetic diagnosis for gender selection in the USA.  

PubMed

Preimplantation genetic diagnosis (PGD) for gender selection for non-medical reasons has been considered an unethical procedure by several authors and agencies in the Western society on the basis that it could disrupt the sex ratio, that it discriminates against women and that it leads to 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 USA 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 embryos transferred of the non-desired gender, this fact being strongly linked to cultural and ethnic 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. PMID:19891844

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

2009-01-01

189

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

190

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

PubMed

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

2012-11-14

191

PGD synthase and PGD2 in immune resposne.  

PubMed

PGD(2) is formed from arachidonic acid by successive enzyme reactions: oxygenation of arachidonic acid to PGH(2), a common precursor of various prostanoids, catalyzed by cyclooxygenase, and isomerization of PGH(2) to PGD(2) by PGD synthases (PGDSs). PGD(2) can be either pro- or anti-inflammatory depending on disease process and etiology. The anti-inflammatory and immunomodulatory attributes of PGDS/PGD(2) provide opportunities for development of novel therapeutic approaches for resistant infections and refractory inflammatory diseases. This paper highlights the role of PGD synthases and PGD2 in immune inflammatory response. PMID:22791937

Joo, Myungsoo; Sadikot, Ruxana T

2012-06-25

192

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

PubMed

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

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

2012-03-07

193

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

PubMed Central

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

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

2012-01-01

194

Queerin' the PGD clinic : human enhancement and the future of bodily diversity.  

PubMed

Disability activists influenced by queer theory and advocates of "human enhancement" have each disputed the idea that what is "normal" is normatively significant, which currently plays a key role in the regulation of pre-implantation genetic diagnosis (PGD). Previously, I have argued that the only way to avoid the implication that parents have strong reasons to select children of one sex (most plausibly, female) over the other is to affirm the moral significance of sexually dimorphic human biological norms. After outlining the logic that generates this conclusion, I investigate the extent to which it might also facilitate an alternative, progressive, opening up of the notion of the normal and of the criteria against which we should evaluate the relative merits of different forms of embodiment. This paper therefore investigates the implications of ideas derived from queer theory for the future of PGD and of PGD for the future of queerness. PMID:23468396

Sparrow, Robert

2013-06-01

195

Comparison of blastocyst transfer with or without preimplantation genetic diagnosis for aneuploidy screening in couples with advanced maternal age: a prospective randomized controlled trial  

Microsoft Academic Search

BACKGROUND: It is generally accepted that the age-related increased aneuploidy rate is correlated with reduced implantation and a higher abortion rate. Therefore, advanced maternal age (AMA) couples are a good target group to assess the possible benefit of preimplantation genetic diagnosis for aneuploidy screening (PGD-AS) on the outcome after assisted reproductive technology (ART). METHODS: A prospective randomized controlled clinical trial

Catherine Staessen; Peter Platteau; Elvire Van Assche; An Michiels; Herman Tournaye; Michel Camus; Paul Devroey; Inge Liebaers; AndreVan Steirteghem

2004-01-01

196

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

197

Preimplantation diagnosis of genetic diseases.  

PubMed

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

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

198

Heterozygosity assessment of five STR loci located at 5q13 region for preimplantation genetic diagnosis of spinal muscular atrophy.  

PubMed

Preimplantation genetic diagnosis (PGD) has been considered as an alternative to prenatal diagnosis for prevention of genetic disorders while avoiding the subsequent termination of pregnancy. However, the limited amount of template DNA available in a single diploid cell used for PGD leads to number of problems including an increased incidence of detectable contamination; amplification failure and allele drop out. Due to their highly polymorphic and amplifiable characteristics, short tandem repeat (STR) analysis has been proposed as a mean to overcome these limitations. Heterozygosity of the applied STRs is of paramount importance in their informativity, and should therefore be studied in any certain population. Here, for the first time, we report on the heterozygosity analysis of five STR markers (D5S1408, D5S1417, D5S610, D5S629 and D5S637) flanking to SMA gene region, to examine their applicability in the PGD for SMA disease. We have also investigated other statistical features of these markers and found that all of the five studied STRs were informative and four meet the Hardy-Weinberg equilibrium for the studied population. Furthermore, our results propose that similar approaches can be used for the PGD of other single gene disorders. PMID:23132709

Korzebor, Asghar; Derakhshandeh-Peykar, Pupak; Meshkani, Mohsen; Hoseini, Azadeh; Rafati, Maryam; Purhoseini, Marzieh; Ghaffari, Saeed Reza

2012-11-07

199

[Molecular genetics and prenatal diagnosis].  

PubMed

Recombinant DNA techniques have provided new insight into genetic and prenatal diagnosis during the last 10 years. Human gene mapping data are increasing exponentially due to molecular biology advances. Most analyses are possible from chorionic villi biopsy specimens as early as the 10th week of fetal life. When the gene is known and cloned, the diagnosis is regularly made by using the polymerase chain reaction technique; when the gene is unknown but mapped, the restriction fragment length polymorphism technique is used. However, these methods for prenatal assessment require a reliable diagnosis of index case disease and a preliminary familial DNA study. PMID:1359503

Lyonnet, S; Rozet, J M; Martin, C; Munnich, A

1992-01-01

200

Prenatal Diagnosis of Genetic Disorders  

Microsoft Academic Search

Sampling of amniotic fluid, visualization of the fetus, fetal blood sampling, and screening of maternal blood represent successive approaches to the diagnosis of specific genetic disorders in the second trimester of pregnancy. Clinical and ethical concerns about the appropriateness, safety, and efficacy of the techniques have led to multidisciplinary assessments at an early stage. A major growth in demand for

Gilbert S. Omenn

1978-01-01

201

First successful double-factor PGD for Lynch syndrome: monogenic analysis and comprehensive aneuploidy screening.  

PubMed

Preimplantation genetic diagnosis (PGD) has been applied worldwide for a great variety of single-gene disorders over the last 20?years. The aim of this work was to perform a double-factor preimplantation genetic diagnosis (DF-PGD) protocol in a family at risk for Lynch syndrome. The family underwent a DF-PGD approach in which two blastomeres from each cleavage-stage embryo were biopsied and used for monogenic and comprehensive cytogenetic analysis, respectively. Fourteen embryos were biopsied for the monogenic disease and after multiple displacement amplification (MDA), 12 embryos were diagnosed; 5 being non-affected and 7 affected by the disease. Thirteen were biopsied to perform the aneuploidy screening by short-comparative genomic hybridization (CGH). The improved DF-PGD approach permitted the selection of not only healthy but also euploid embryos for transfer. This has been the first time a double analysis of embryos has been performed in a family affected by Lynch syndrome, resulting in the birth of two healthy children. The protocol described in this work offers a reliable alternative for single-gene disorder assessment together with a comprehensive aneuploidy screening of the embryos that may increase the chances of pregnancy and birth of transferred embryos. PMID:22998423

Daina, G; Ramos, L; Obradors, A; Rius, M; Martinez-Pasarell, O; Polo, A; Del Rey, J; Obradors, J; Benet, J; Navarro, J

2012-10-17

202

First clinical application of comparative genomic hybridization and polar body testing for preimplantation genetic diagnosis of aneuploidy  

Microsoft Academic Search

Objective: To develop a preimplantation genetic diagnosis (PGD) protocol that allows any form of chromosome imbalance to be detected.Design: Case report employing a method based on whole-genome amplification and comparative genomic hybridization (CGH).Setting: Clinical IVF laboratory.Patient(s): A 40-year-old IVF patient.Intervention(s): Polar body and blastomere biopsy.Main Outcome Measure(s): Detection of aneuploidy.Result(s): Chromosome imbalance was detected in 9 of 10 polar bodies.

Dagan Wells; Tomas Escudero; Brynn Levy; Kurt Hirschhorn; Joy D. A Delhanty; Santiago Munné

2002-01-01

203

Simultaneous enumeration of chromosomes 13, 18, 21, X, and Y in interphase cells for preimplantation genetic diagnosis of aneuploidy  

Microsoft Academic Search

A fluorescence in situ hybridization (FISH) protocol to simultaneously enumerate chromosomes 13, 18, 21, X, and Y in interphase cell nuclei for application in preimplantation genetic diagnosis (PGD) of aneuploidy was tested. Strict scoring criteria were developed to minimize recording errors. The protocol used optimized probes for chromosome-specific DNA repeat and single-copy loci and showed a significantly higher efficiency (95%)

S. Munné; H.-U. G. Weier

1996-01-01

204

Healthy births and ongoing pregnancies obtained by preimplantation genetic diagnosis in patients with advanced maternal age and recurrent implantation failure  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) and subsequent embryo development was evaluated in 72 couples presenting at our centre for intracytoplasmic sperm injection (ICSI) due to severe male factor. The embryo biopsies were performed in Ca2\\/Mg2-free medium. These patients were further divided into those with advanced maternal age (AMA, n 49) and those with recurrent implantation failure (RIF, n 23). Fluorescence in-situ

S. Kahraman; M. Bahce; H. Samlõ; N. I úmirzalõog ùlu; K. Yakõsn; G. Cengiz; E. Donmez

2000-01-01

205

The use of preimplantation genetic diagnosis in sex selection for family balancing in India.  

PubMed

This paper describes the use of preimplantation genetic diagnosis (PGD) in sexing embryos for family balancing in a private IVF clinic in India from April 1999 to April 2001. Embryos were biopsied and analysed on day 3, cultured in sequential media and then transferred on day 4 or day 5 after morphological selection of the best embryos. From a total of 42 cycles started, 14 clinical pregnancies and nine live births have been achieved so far, with five ongoing pregnancies. The benefits of delayed transfer 24-48 h after the embryo biopsy are that PGD centres could use the extra time available to confirm the diagnosis or introduce additional diagnostic tests for the same embryo. The selection of blastocysts for transfer should also permit the transfer of fewer embryos, thus reducing the risk of multiple gestations and increasing the pregnancy rate as a consequence of the expected higher implantation rate. This is the first report of the use of PGD in sex selection for family balancing in India, where couples place a premium on having baby boys, and the social and ethical aspects of the use of this technology in this setting are briefly discussed. PMID:12470347

Malpani, A; Malpani, A; Modi, D

206

Platelet PGD Test System (2009)  

Center for Biologics Evaluation and Research (CBER)

... Platelet PGD Test System (2009). Applicant: Verax Biomedical Incorporated. 510(k) number: BK090028. Product: Platelet PGD Test System. ... More results from www.fda.gov/biologicsbloodvaccines/bloodbloodproducts/approvedproducts

207

Preimplantation genetic haplotyping a new application for diagnosis of translocation carrier’s embryos preliminary observations of two robertsonian translocation carrier families  

Microsoft Academic Search

Purpose  Preimplantation genetic diagnosis using fluorescence in-situ hybridization (PGD-FISH) is currently the most common reproductive\\u000a solution for translocation carriers. However, this technique usually does not differentiate between embryos carrying the balanced\\u000a form of the translocation and those carrying the homologous normal chromosomes. We developed a new application of preimplantation\\u000a genetic haplotyping (PGH) that can identify and distinguish between all forms of

Jana Shamash; Shlomit Rienstein; Haike Wolf-Reznik; Elon Pras; Michal Dekel; Talia Litmanovitch; Masha Brengauz; Boleslav Goldman; Hagith Yonath; Jehoshua Dor; Jacob Levron; Ayala Aviram-Goldring

2011-01-01

208

SNP array-based copy number and genotype analyses for preimplantation genetic diagnosis of human unbalanced translocations  

PubMed Central

Preimplantation genetic diagnosis (PGD) for chromosomal rearrangements (CR) is mainly based on fluorescence in situ hybridisation (FISH). Application of this technique is limited by the number of available fluorochromes, the extensive preclinical work-up and technical and interpretative artefacts. We aimed to develop a universal, off-the-shelf protocol for PGD by combining single-nucleotide polymorphism (SNP) array-derived copy number (CN) determination and genotyping for detection of unbalanced translocations in cleavage-stage embryos. A total of 36 cleavage-stage embryos that were diagnosed as unbalanced by initial PGD FISH analysis were dissociated (n=146) and amplified by multiple displacement amplification (MDA). SNP CNs and genotypes were determined using SNP array. Epstein-Barr Virus-transformed cell lines with known CR were used for optimising the genomic smoothing (GS) length setting to increase signal to noise ratio. SNP CN analysis showed 23 embryos (64%) that were unbalanced in all blastomeres for the chromosomes involved in the translocation, 5 embryos (14%) that were normal or balanced in all blastomeres and 8 embryos (22%) that were mosaic. SNP genotyping, based on analysis of informative SNP loci with opposing homozygous parental genotypes, confirmed partial monosomies associated with inheritance of unbalanced translocation in surplus embryos. We have developed a universal MDA-SNP array technique for chromosome CN analysis in single blastomeres. SNP genotyping could confirm partial monosomies. This combination of techniques showed improved diagnostic specificity compared with FISH and may provide more reliable PGD analysis associated with higher embryo transfer rate.

van Uum, Chris MJ; Stevens, Servi JC; Dreesen, Joseph CFM; Drusedau, Marion; Smeets, Hubert J; Hollanders-Crombach, Bertien; Die-Smulders, Christine EM de; Geraedts, Joep PM; Engelen, John JM; Coonen, Edith

2012-01-01

209

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

PubMed

Many couples are now seeking preimplantation genetic diagnosis (PGD) and fluorescence in-situ hybridization (FISH) as an alternative approach to avoid spontaneous abortion by ensuring transfer of presumed chromosomally normal embryos. This case report describes unexpected findings in a couple having three spontaneous abortions and two failed IVF cycles. In two IVF PGD cycles, four of 13 (30.8%) embryos (blastomeres) demonstrated duplication involving the Down syndrome critical region, detectable by a locus specific chromosome 21 probe. The same duplication was subsequently detected by FISH in 66 of 1002 (6.6%) sperm nuclei, demonstrating paternal gonadal mosaicism. Cytogenetic studies of peripheral blood revealed normal karyotypes in both the male and female partners. This identification of paternal germ cell or gonadal mosaicism suggests that analysis of sperm nuclei prior to undergoing IVF with PGD may be of value in patients with recurrent spontaneous abortions or multiple failed IVF. PMID:15333256

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

2004-08-01

210

Single-cell polymerase chain reaction-based pre-implantation genetic diagnosis using fragment analysis for ?-thalassemia in an Indian couple with ?-globin gene mutations.  

PubMed

Despite advances in diagnostic techniques, approximately 10,000 babies with ?-thalassemia major are born annually in India. Pre-implantation genetic diagnosis (PGD), an alternative to prenatal diagnosis, helps in negative selection of affected embryos prior to implantation. Hereby, we report the first successful ?-thalassemia PGD pregnancy in an Indian carrier couple. ?-Thalassemia mutation analysis by Amplification-Refractory Mutation Sequence (ARMS)-polymerase chain reaction (PCR) in the parents, followed by PGD for ?-thalassemia mutation in embryos in two consequent in vitro fertilization (IVF) cycles, with transfer for three ?-thalassemia minor embryos, resulted in singleton successful pregnancy, the results of which were confirmed on prenatal diagnosis. With advances in assisted reproductive techniques and molecular diagnosis, PGD for monogenic diseases is feasible in high-risk couples. The methodology in the current study included two rounds of PCR using fluorescently labeled primers, fragment analysis using the ABI 3100 nucleotide sequencer and the GeneMapper software, purification, and concentration of PCR product, which enabled distinct clear peaks making the analysis and interpretation non-ambiguous. PMID:23532358

Gada Saxena, Shailaja; Saranath, Dhananjaya

2012-09-01

211

Rapid and powerful decaplex and dodecaplex PGD protocols for Duchenne muscular dystrophy.  

PubMed

Duchenne muscular dystrophy (DMD) is a common childhood lethal X-linked recessive disorder, resulting from deletions, duplications and point mutations in the dystrophin gene. Single-cell protocols for preimplantation genetic diagnosis (PGD) still remain challenging due to the enormous size of the gene and the high risk of intragenic recombination, limitations that often lead to sex determination and selection of female embryos. This study describes direct and rapid decaplex and dodecaplex polymerase chain reaction protocols enabling the analysis of five or seven exons and four microsatellite markers scattered along the dystrophin gene, chosen to be located in the two deletion hotspots, and the analysis of amelogenin sequences for gender determination. The dodecaplex protocol may be applied to most of the couples requesting PGD for DMD in whom the female partner is a carrier of a deletion. This generic approach will allow prompt response to the PGD referrals by reducing the pre-clinical PGD work-up. It was successfully applied in three DMD families, resulting in the birth of a girl as well as in a healthy ongoing pregnancy. PMID:20031025

Girardet, A; Fernandez, C; Claustres, M

2009-12-01

212

Single-cell DNA and FISH analysis for application to preimplantation genetic diagnosis.  

PubMed

Preimplantation genetic testing, which includes preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS), is a form of a very early prenatal testing. The goal of this method is to avoid transfer of embryos affected with a specific genetic disease or condition. This unit describes the steps involved in amplifying DNA from a single blastomere and specific assays for detecting a variety of DNA mutations. For some assays, whole-genome amplification by primer-extension preamplification (PEP) is performed prior to analysis. Support protocols describe the biopsy of one or two blastomeres from the developing preimplantation embryo, isolation for further investigation of all blastomeres from embryos shown to have the mutant allele, and isolation of single lymphocytes or lymphoblastoid cells as models for single-cell DNA analysis. A procedure for FISH analysis on single interphase blastomeres is provided along with support protocols for probe preparation and probe validation, which is recommended as a preliminary step before performing any PGD or PGS FISH analysis. PMID:20063266

Chong, Samuel S; Gore-Langton, Robert E; Hughes, Mark R; Weremowicz, Stanislawa

2010-01-01

213

Assessing congenital anomalies after preimplantation genetic diagnosis  

Microsoft Academic Search

Background: Preimplantation genetic diagnosis is an exciting advance in prenatal diagnosis. However, the safety of embryo biopsy must be determined with respect to both pregnancy rate and cogenital anomalies.

Joe Leigh Simpson; Inge Liebaers

1996-01-01

214

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

2013-05-04

215

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

PubMed

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

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

2013-07-25

216

Single cell co-amplification of polymorphic markers for the indirect preimplantation genetic diagnosis of hemophilia A, X-linked adrenoleukodystrophy, X-linked hydrocephalus and incontinentia pigmenti loci on Xq28  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) first consisted of the selection of female embryos for patients at risk of transmitting X-linked recessive diseases. Advances in molecular biology now allow the specific diagnosis of almost any Mendelian disease. For families with an identified X-linked recessive disease-causing mutation, non-specific diagnosis by sex identification can be considered as a sub-standard method, since it involves the

Nadine Gigarel; Nelly Frydman; Philippe Burlet; Violaine Kerbrat; Julie Steffann; René Frydman; Arnold Munnich; Pierre F. Ray

2004-01-01

217

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

PubMed

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

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

2007-11-01

218

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

219

Derivation of new human embryonic stem cell lines from preimplantation genetic screening and diagnosis-analyzed embryos.  

PubMed

In this study, we focused on the derivation of human embryonic stem cell (hESC) from preimplantation genetic screening (PGS)-analyzed and preimplantation genetic diagnosis (PGD)-analyzed embryos. Out of 62 fresh PGD/PGS-analyzed embryos, 22 embryos reached the blastocyst stage. From 12 outgrowth blastocysts, we derived four hESC lines onto a feeder layer. Surprisingly, karyotype analysis showed that hESC lines derived from aneuploid embryos had diploid female karyotype. One hESC line was found to carry a balanced Robertsonian translocation. All the cell lines showed hESC markers and had the pluripotent ability to differentiate into derivatives of the three embryonic germ layers. The established lines had clonal propagation with 22-31% efficiency in the presence of ROCK inhibitor. These results further indicate that hESC lines can be derived from PGD/PGS-analyzed embryos that are destined to be discarded and can serve as an alternative source for normal euploid lines. PMID:20177993

Taei, Adeleh; Gourabi, Hamid; Seifinejad, Ali; Totonchi, Mehdi; Shahbazi, Ebrahim; Valojerdi, Mojtaba Rezazadeh; Eftekhari, Poopak; Karimian, Leila; Baharvand, Hossein

2010-02-23

220

A versatile strategy for preimplantation genetic diagnosis of haemophilia A based on F8-gene sequencing.  

PubMed

Preimplantation genetic diagnosis (PGD) of hemophilia A (HA) and other X-linked diseases through sex selection implies that male embryos will be systematically discarded, even though 50% are unaffected. The objective of the present work was to develop a PGD protocol for direct mutation identification that could be applied to first polar bodies (1PBs) in several HA clinical cases. Single buccal cells from controls and patients, and 1PBs were subjected to primer extension preamplification (PEP) PCR followed by amplification of F8 gene coding and intronic flanking regions, and direct sequencing. Moreover, multiplex fluorescent amplification of four short tandem repeats was adapted to a single cell preamplification in order to rule out contamination and allele drop-out, and for confirmatory indirect diagnosis. A couple at risk of HA transmission, with a familial mutation characterized as a 41-bp duplication in exon 14 of the F8 gene, was selected for the first clinical study. After optimizing the protocol, the complete F8 gene coding sequence was obtained from single cells to demonstrate the sensitivity of our methodology although in any clinical case only the relevant region, not the whole gene, must be amplified. The woman enrolled in the first clinical case has completed the first in-vitro fertilization cycle, and seven oocytes were analyzed with concordant results by both linkage analysis and direct sequencing method. Only one oocyte, among those diagnosed as mutation free, developed to embryo at day 3. It was transferred but pregnancy was not achieved. This PGD procedure enables non-affected and noncarrier embryo selection in families with any point or small-range mutation in the F8 gene, without the need for further custom-made modifications. PMID:17139381

Sánchez-García, Jorge F; Gallardo, Dominique; Navarro, Joaquima; Márquez, Carmen; Gris, Josep Maria; Sánchez, Maria Angeles; Altisent, Carme; Vidal, Francisco

2006-12-01

221

Non-informative results and monosomies in PGD: the importance of a third round of re-hybridization  

Microsoft Academic Search

The incidence of non-informative results after fluorescence in-situ hybridization (FISH) was analysed in preimplantation genetic diagnosis (PGD). FISH was performed on seven chromosomes (13, 16, 18, 21, 22, X, and Y) in two rounds of hybridization (one biopsied blastomere per day 3 embryo). A third round with telomeric probes was performed in order to analyse the chromosome(s) in question. A

Petr Uher; Petra Baborova; Milena Kralickova; Mathias H. Zech; Yury Verlinsky; Nicolas H. Zech

2009-01-01

222

Preimplantation Genetic Diagnosis for Aneuploidy and Translocations Using Array Comparative Genomic Hybridization  

PubMed Central

At least 50% of human embryos are abnormal, and that increases to 80% in women 40 years or older. These abnormalities result in low implantation rates in embryos transferred during in vitro fertilization procedures, from 30% in women <35 years to 6% in women 40 years or older. Thus selecting normal embryos for transfer should improve pregnancy results. The genetic analysis of embryos is called Preimplantation Genetic Diagnosis (PGD) and for chromosome analysis it was first performed using FISH with up to 12 probes analyzed simultaneously on single cells. However, suboptimal utilization of the technique and the complexity of fixing single cells produced conflicting results. PGD has been invigorated by the introduction of microarray testing which allows for the analysis of all 24 chromosome types in one test, without the need of cell fixation, and with staggering redundancy, making the test much more robust and reliable. Recent data published and presented at scientific meetings has been suggestive of increased implantation rates and pregnancy rates following microarray testing, improvements in outcome that have been predicted for quite some time. By using markers that cover most of the genome, not only aneuploidy can be detected in single cells but also translocations. Our validation results indicate that array CGH has a 6Mb resolution in single cells, and thus the majority of translocations can be analyzed since this is also the limit of karyotyping. Even for translocations with smaller exchanged fragments, provided that three out of the four fragments are above 6Mb, the translocation can be detected.

Munne, Santiago

2012-01-01

223

A molecular strategy for routine preimplantation genetic diagnosis in both reciprocal and Robertsonian translocation carriers.  

PubMed

Preimplantation genetic diagnosis (PGD) for structural chromosome abnormalities traditionally uses fluorescence in situ hybridization (FISH) techniques. Although relatively straight forward, FISH is technically demanding with several process problems which include cell loss, cell overlap, variable cell fixation and hybridization as well as sample mosaicism. Increasingly, alternative techniques for chromosome analysis in embryos are being investigated in an attempt to improve on current test outcomes. Here, we report on the first routine application of a polymerase chain reaction (PCR)-based protocol for translocation analysis utilizing multiplexed short tandem repeat (STR) markers located on both segments of the translocated chromosomes. Resulting STR profiles permit the analysis of qualitative dosage of each chromosomal segment to identify translocation malsegregants from the balanced/normal chromosome complements. A total of 29 patients have undergone clinical PGD testing of 78 embryos using this method. The proportion of alternate segregations (i.e. balanced carrier and non-carriers) detected for reciprocal and Robertsonian translocation carriers was 33% and 77%, respectively. Fetal heart pregnancy rates per embryo transferred was 46% for reciprocal carriers and 40% for Robertsonian carriers (mean number of embryos transferred was 1.0). This novel approach can be applied easily within any existing PGD PCR laboratory and allows for a significant improvement in the identification of segregation types when compared with the standard FISH protocol using combinations of distal and proximal probes. This approach increases test robustness and reliability with improved interpretation of segregation outcomes, decreased analysis time and also enables the straight forward combining of structural chromosome analysis with monogenic testing. PMID:20172975

Traversa, M V; Carey, L; Leigh, D

2010-02-19

224

Diagnosis of genetic disease using recombinant DNA  

Microsoft Academic Search

Recombinant DNA technology promises to make an important contribution to the analysis and diagnosis of inherited human disease. Direct detection and analysis of various genetic defects at the DNA level are now possible using cloned gene or oligonucleotide probes. In addition, the use of restriction fragment length polymorphisms associated with linked DNA segments should permit not only the diagnosis of

D. N. Cooper; J. Schmidtke

1986-01-01

225

Successful PGD cycles for mosaic Robertsonian translocation carriers provide insights into the mechanism of formation of the derivative chromosomes.  

PubMed

Preimplantation genetic diagnosis (PGD) has been carried out for two couples with different mosaic Robertsonian translocations. Two PGD cycles for a mosaic 13;13 homologous Robertsonian translocation carrier resulted in the birth of a healthy child in each cycle, illustrating the importance of scanning G-banded preparations from homologous Robertsonian carriers for the presence of a normal cell line. One couple was referred for PGD because the male partner carried a mosaic 14;15 Robertsonian translocation with a normal cell line. A single PGD cycle resulted in the birth of a healthy child. Follow-up studies and extended FISH analysis of the carrier's lymphocytes detected three cell lines, two carrying different 14;15 Robertsonian chromosomes and one normal cell line. The two 14;15 Robertsonian chromosomes had different breakpoints in the proximal short arm regions. We suggest that the presence of the D15Z1 polymorphism on the short arm of one chromosome 14 mediated the post-zygotic formation of the two different Robertsonian chromosomes. PMID:23401053

Bint, Susan M; Scriven, Paul N; Ogilvie, Caroline Mackie

2013-02-07

226

PGD gender selection for non-Mendelian disorders with unequal sex incidence.  

PubMed

Preimplantation genetic diagnosis (PGD) was originally developed for couples whose potential offspring were at risk of severe Mendelian disorders, but has since been extended to other indications. One possible use of PGD is to perform gender selection for couples whose offspring are at increased risk of disorders that do not follow Mendelian inheritance, but which are substantially more common in one sex than another (unequal sex incidence). Here, we examine the clinical and ethical issues to be considered prior to offering PGD gender selection to reduce the risk of a child being affected by a non-Mendelian condition with unequal sex incidence. Factors to be considered include: the risk that a child of either sex will be affected by the condition; the overall reduction in risk provided by gender selection and the potential harms of the procedure. Consideration should also be given to the interests of the family and the child to be born, the seriousness of the condition and the couple's procreative autonomy. To illustrate these issues we use the example of autism, a non-Mendelian disorder that is considerably more common in males than in females. PMID:18222917

Amor, David J; Cameron, Carolyn

2008-01-24

227

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

228

Successful Live Birth following Preimplantation Genetic Diagnosis for Phenylketonuria in Day 3 Embryos by Specific Mutation Analysis and Elective Single Embryo Transfer.  

PubMed

Phenylketonuria (PKU) is an autosomal recessive inherited metabolic disorder caused by a complete or near-complete deficiency of the liver enzyme phenylalanine hydroxylase (PAH), which converts the amino acid phenylalanine to tyrosine, leading to the increase of blood and tissue concentration of phenylalanine to toxic levels. PKU is not life threatening but is treated through lifelong dietary management. If untreated, it can lead to severe learning disability, brain function abnormalities, behavioural and neurological problems. The non-life threatening nature of PKU has until now caused some debate on whether to licence its detection by preimplantation genetic diagnosis (PGD). We report the first successful live birth in the UK following single cell embryo biopsy and PGD for the detection of two different mutations in the (PAH) gene. This case highlights both an important scientific development as well as the ethical challenge in offering couples who carry PKU this new reproductive option when starting their family. PMID:23430494

Lavery, Stuart; Abdo, Dima; Kotrotsou, Mara; Trew, Geoff; Konstantinidis, Michalis; Wells, Dagan

2012-03-31

229

DNA diagnosis of human genetic individuality  

Microsoft Academic Search

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

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

1995-01-01

230

BK070044, Platelet PGD Test System  

Center for Biologics Evaluation and Research (CBER)

Text Version... INCORPORATED Platelet PGD ® Test ... The Platelet PGD Test should not be used in determining suitability for release of LRAP for transfusion. ... More results from www.fda.gov/downloads/biologicsbloodvaccines/bloodbloodproducts

231

Preimplantation genetic screening: do we need a degree of caution?  

Microsoft Academic Search

Preimplantation genetic diagnosis (PGD) is a form of very early prenatal diagnosis. The technique combines assisted reproductive technology with molecular and cyto-genetics to allow the identification of abnormalities in embryos prior to implantation. Advancing maternal age is associated with a reduction in oocyte quality due to an increase in meiotic errors, possibly compounded by poor follicular vascularisation, oxidative damage and

Stuart Lavery

2007-01-01

232

Preimplantation Genetic Diagnosis for Stargardt Disease  

PubMed Central

Purpose To report the first use of in vitro fertilization (IVF) and preimplantation genetic diagnosis to achieve an unaffected pregnancy in an autosomal-recessive retinal dystrophy. Design Case report. Methods An affected male with Stargardt disease and his carrier wife underwent IVF. Embryos obtained by intracytoplasmic sperm injection underwent single-cell DNA testing via polymerase chain reaction and restriction enzyme analysis to detect the presence of ABCA4 mutant alleles. Embryos were diagnosed as being either affected by or carriers for Stargardt disease. A single carrier embryo was implanted. Results Chorionic villus sampling performed during the first trimester verified that the fetus possessed only one mutant paternal allele and one normal maternal allele, thus making her an unaffected carrier of the disease. A healthy, live-born female was delivered. Conclusion IVF and preimplantation genetic diagnosis can assist couples with an affected spouse and a carrier spouse with recessive retinal dystrophies to have an unaffected child.

Sohrab, Mahsa A.; Allikmets, Rando; Guarnaccia, Michael M.; Smith, R. Theodore

2010-01-01

233

Plasmonic DNA: Towards Genetic Diagnosis Chips  

Microsoft Academic Search

The present paper summarizes some of our activities in the field of plasmonic DNA and genetic diagnosis, presenting our system\\u000a and its capabilities before showing data related to the design and use of functionalized biochips of increasing complexity\\u000a along with various experimental hybridization conditions, including solutions containing one type of purified synthetic short\\u000a oligonucleotides or PCR-amplified DNA samples from patients.

Jérôme Hottin; Julien Moreau; Gisèle Roger; Jolanda Spadavecchia; Marie-Claude Millot; Michel Goossens; Michael Canva

2007-01-01

234

Genetic diagnosis of hyperkinetic movement disorders.  

PubMed

Introduction: People with hyperkinetic movements have always attracted the attention of the public and professionals. Alert colleagues noticed families in which a disease passed from generation to generation around Lake Maracaibo in Venezuela. This study led in 1993 to the localization of the gene for Huntington disease on chromosome 4. The genetic basis of many other familial and sporadic diseases has been identified on human DNA. Areas covered: The clinical presentation of hyperkinesias remains the starting point for diagnosis, but differential diagnosis is a long, difficult process, the first step being to differentiate between inherited and non-inherited forms. The need to know the diagnosis is of major importance for patient and family. Knowledge about the cause limits the number of extra diagnostics. This review of the literature presents the most frequently occurring genetically-determined forms of hyperkinesias, mainly chorea and dystonia and tries to give some practical guidelines. Expert opinion: The final part of the review will offer some thoughts and views for future development in a world which probably has more knowledge than we can handle. The drive to find a diagnosis is rewarded by the patient but one also needs to reflect on the use of medical care. PMID:23480808

Roos, Raymund Ac

2012-07-13

235

Genetic issues in the diagnosis of dystonias.  

PubMed

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

2013-04-10

236

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.

Ehrich, Kathryn; Williams, Clare; Farsides, Bobbie

2008-01-01

237

Identification of embryonic chromosomal abnormality using FISH-based preimplantaion genetic diagnosis  

Microsoft Academic Search

Objective: Embryonic chromosomal abnormality is one of the main reasons for in vitro fertilization (IVF) failure. This study aimed at evaluating the value of Fluorescence in-situ Hybridization (FISH)-based Preimplantation Ge- netic Diagnosis (PGD) in screening for embryonic chromosomal abnormality to increase the successful rate of IVF. Method: Ten couples, four with high risk of chromosomal abnormality and six infertile couples,

YE Ying-hui; XU Chen-ming; QIAN Yu-li

238

Molecular genetic methods in diagnosis and treatment.  

PubMed

During the past 20 yr, molecular biology and molecular genetics have provided techniques and procedures that allow the precise diagnoses of leukemias and lymphomas (for a review, see ref. 1). These methodologies have provided powerful, robust, and precise characterizations of genetic mutations and gene rearrangements (both normal and abnormal) that have been applied to the diagnosis and treatment of these malignancies. In this chapter we discuss methodologies currently utilized within the molecular diagnostic laboratory of cancer centers and major academic hospitals. We introduce these methodologies in both general terms and within the context of a differential diagnosis of leukemia/lymphoma. The long-term goal of the molecular hematologist/oncologist is to describe all mutations that occur within a given type or subtype of leukemia/lymphoma. This involves the discovery of new somatic and possibly hereditary mutations that contribute to the genesis of these hematologic malignancies. However, for this information to be useful in treatment regimens, therapies that target or affect these growth-dysregulating mutations must be found. Because diagnosis of mutation and gene rearrangement in the hematologic malignancies is far ahead of therapeutic modalities, we also discuss new research tools that will have impact on the experimental hematologist. PMID:21312105

Ward, P; Kinniburgh, A

2001-01-01

239

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

PubMed

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

Sills, E Scott; Palermo, Gianpiero D

2002-09-01

240

Use of preimplantation genetic diagnosis for serious adult onset conditions: a committee opinion.  

PubMed

PGD for adult-onset conditions is ethically justified when the condition is serious and no safe, effective interventions are available. It is ethically allowed for conditions of lesser severity or penetrance. The Committee strongly recommends that an experienced genetic counselor play a major role in counseling patients considering such procedures. PMID:23477677

2013-03-07

241

Personal desires of patients and social obligations of geneticists: applying preimplantation genetic diagnosis for non-medical sex selection.  

PubMed

The arguments against the use of preimplantation genetic diagnosis (PGD) for non-medical sex selection are analysed. It is concluded that the distinction between medical and non-medical reasons is difficult to maintain, that the disproportionality of means and end is not a decisive counterargument and that the fear of damage to the reputation of PGD does not justify the refusal of controversial applications. Moreover, since non-medical sex selection does not belong to basic health care, it should not be equally accessible to all. The position defended in this article is founded on two basic principles: (1). medical reasons have priority on non-medical reasons, and (2). personal reasons do not qualify for public funding. In order to respect both principles, it is proposed that restrictions should be installed to control the number of requests for social sexing and that a tax should be imposed on these elective services. The tax should compensate the society for the investment it made in the training and education of the physician. PMID:12454971

Pennings, Guido

2002-12-01

242

Healthy births and ongoing pregnancies obtained by preimplantation genetic diagnosis in patients with advanced maternal age and recurrent implantation failure.  

PubMed

Preimplantation genetic diagnosis (PGD) and subsequent embryo development was evaluated in 72 couples presenting at our centre for intracytoplasmic sperm injection (ICSI) due to severe male factor. The embryo biopsies were performed in Ca(2+)/Mg(2+)-free medium. These patients were further divided into those with advanced maternal age (AMA, n = 49) and those with recurrent implantation failure (RIF, n = 23). Fluorescence in-situ hybridization (FISH) was carried out on 329 blastomeres (91.3%) with probes for the X, Y, 13, 18 and 21 chromosomes. The chromosomal abnormality rate was 41.3% with no significant difference between the AMA and RIF groups. Aneuploidy accounted for the majority (72.8%) of chromosomal abnormalities. Out of 329 embryos, 84.2% had cleaved after 24 h and 15.1% had arrested. Embryos were transferred in 70 patients and 22 pregnancies were achieved (31.4% with an ongoing pregnancy rate of 28.5%). There were no significant differences between the pregnancy rates of the AMA and RIF groups (32.5 and 30% respectively). Therefore PGD should be offered to patients with AMA and RIF. Furthermore, the use of Ca(2+)/Mg(2+)-free medium during the blastomere biopsy facilitates the procedure, while further embryo cleavage, ongoing pregnancies and healthy births are possible. PMID:10967004

Kahraman, S; Bahçe, M; Samli, H; Imirzalio?lu, N; Yakisn, K; Cengiz, G; Dönmez, E

2000-09-01

243

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

PubMed Central

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

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

2012-01-01

244

Characterization of human PGD blastocysts with unbalanced chromosomal translocations and human embryonic stem cell line derivation?  

PubMed

Novel embryonic stem cell lines derived from embryos carrying structural chromosomal abnormalities obtained after preimplantation genetic diagnosis (PGD) are of interest to study in terms of the influence of abnormalities on further development. A total of 22 unbalanced blastocysts obtained after PGD were analysed for structural chromosomal defects. Morphological description and chromosomal status of these blastocysts was established and they were used to derive human embryonic stem cell (ESC) lines. An outgrowth of cells was observed for six blastocysts (6/22; 27%). For two blastocysts, the exact morphology was unknown since they were at early stage, and for four blastocysts, the inner cell mass was clearly visible. Fifteen blastocysts carried an unbalanced chromosomal defect linked to a reciprocal translocation, resulting in a positive outgrowth of cells for five blastocysts. One human ESC line was obtained from a blastocyst carrying a partial chromosome-21 monosomy and a partial chromosome-1 trisomy. Six blastocysts carried an unbalanced chromosomal defect linked to a Robertsonian translocation, and one showed a positive outgrowth of cells. One blastocyst carried an unbalanced chromosomal defect linked to an insertion and no outgrowth was observed. The efficiency of deriving human ESC lines with constitutional chromosomal disorders was low and probably depends on the initial morphological aspect of the blastocysts and/or the type of the chromosomal disorders. PMID:20034412

Frydman, N; Féraud, O; Bas, C; Amit, M; Frydman, R; Bennaceur-Griscelli, A; Tachdjian, G

2009-01-01

245

Prenatal diagnosis: molecular genetics and cytogenetics.  

PubMed

The technologies developed for the Human Genome Project, the recent surge of available DNA sequences resulting from it and the increasing pace of gene discoveries and characterization have all contributed to new technical platforms that have enhanced the spectrum of disorders that can be diagnosed prenatally. The importance of determining the disease-causing mutation or the informativeness of linked genetic markers before embarking upon a DNA-based prenatal diagnosis is, however, still emphasized. Different fluorescence in situ hybridization (FISH) technologies provide increased resolution for the elucidation of structural chromosome abnormalities that cannot be resolved by more conventional cytogenetic analyses, including microdeletion syndromes, cryptic or subtle duplications and translocations, complex rearrangements involving many chromosomes, and marker chromosomes. Interphase FISH and the quantitative fluorescence polymerase chain reaction are efficient tools for the rapid prenatal diagnosis of selected aneuploidies, the latter being considered to be most cost-effective if analyses are performed on a large scale. There is some debate surrounding whether this approach should be employed as an adjunct to karyotyping or whether it should be used as a stand-alone test in selected groups of women. PMID:12475544

Bui, The-Hung; Blennow, Elisabeth; Nordenskjöld, Magnus

2002-10-01

246

Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management.  

PubMed

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

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

2012-01-10

247

Singling out genetic disorders and disease.  

PubMed

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

De Rycke, Martine

2010-10-06

248

Studying potential donors' views on embryonic stem cell therapies and preimplantation genetic diagnosis  

PubMed Central

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

HAIMES, ERICA; LUCE, JACQUELYNE

2008-01-01

249

Successful birth with preimplantation genetic diagnosis using single-cell allele-specific PCR and sequencing in a woman with hypochondroplasia due to FGFR3 mutation (c.1620C>A, p.N540K)  

PubMed Central

Hypochondroplasia (HCH) is an autosomal dominant inherited skeletal dysplasia, usually caused by a heterozygous mutation in the fibroblast growth factor receptor 3 gene (FGFR3). A 27-year-old HCH woman with a history of two consecutive abortions of HCH-affected fetuses visited our clinic for preimplantation genetic diagnosis (PGD). We confirmed the mutation in the proband (FGFR3:c.1620C>A, p.N540K), and established a nested allele-specific PCR and sequence analysis for PGD using single lymphocyte cells. We performed this molecular genetic analysis to detect the presence of mutation among 20 blastomeres from 18 different embryos, and selected 9 embryos with the wild-type sequence (FGFR3:c.1620C). A successful pregnancy was achieved through a frozen-thawed cycle and resulted in the full-term birth of a normal neonate. To the best of our knowledge, this is the first report of a successful pregnancy and birth using single-cell allele-specific PCR and sequencing for PGD in an HCH patient.

Park, Kyung Eui; Kim, Sung Ah; Kang, Moon Joo; Kim, Hee Sun; Cho, Sung Im; Yoo, Kyoung Won; Kim, So Yeon; Lee, Hye Jun; Oh, Sun Kyung; Seong, Moon-Woo; Ku, Seung-Yup; Jun, Jong Kwan; Park, Sung Sup; Moon, Shin Yong

2013-01-01

250

Successful birth with preimplantation genetic diagnosis using single-cell allele-specific PCR and sequencing in a woman with hypochondroplasia due to FGFR3 mutation (c.1620C>A, p.N540K).  

PubMed

Hypochondroplasia (HCH) is an autosomal dominant inherited skeletal dysplasia, usually caused by a heterozygous mutation in the fibroblast growth factor receptor 3 gene (FGFR3). A 27-year-old HCH woman with a history of two consecutive abortions of HCH-affected fetuses visited our clinic for preimplantation genetic diagnosis (PGD). We confirmed the mutation in the proband (FGFR3:c.1620C>A, p.N540K), and established a nested allele-specific PCR and sequence analysis for PGD using single lymphocyte cells. We performed this molecular genetic analysis to detect the presence of mutation among 20 blastomeres from 18 different embryos, and selected 9 embryos with the wild-type sequence (FGFR3:c.1620C). A successful pregnancy was achieved through a frozen-thawed cycle and resulted in the full-term birth of a normal neonate. To the best of our knowledge, this is the first report of a successful pregnancy and birth using single-cell allele-specific PCR and sequencing for PGD in an HCH patient. PMID:23614116

Park, Kyung Eui; Kim, Sung Ah; Kang, Moon Joo; Kim, Hee Sun; Cho, Sung Im; Yoo, Kyoung Won; Kim, So Yeon; Lee, Hye Jun; Oh, Sun Kyung; Seong, Moon-Woo; Ku, Seung-Yup; Jun, Jong Kwan; Park, Sung Sup; Choi, Young Min; Moon, Shin Yong

2013-03-31

251

New methods in genetic diagnosis including prenatal diagnosis.  

PubMed

Recent advances in newborn screening and molecular genetics are transforming our understanding of the genetic basis of diseases that affect individuals of all ages. It is essential for clinicians to understand the methods and goals of newborn screening (NBS), the principles of genetics, and the methods of molecular analysis including Southern blots, PCR amplification, DNA sequence analysis, Reverse Transcriptase PCR, Multiplex Ligation- dependent Probe Amplification analysis, Fluorescence in Situ Hybridization, Comparative Genomic Hybridization, as well as Fetal Ultrasonography. This understanding and applications of these tools can lead to genetic diagnoses by identifying risks from newborn screening results or family histories, selecting appropriate tests and understanding the implications of test results to the patient and their families. To facilitate this understanding we will review newborn screening, basic genetics, inheritance and examples of established and new methods used in genetic testing. It is our hope that this material will facilitate clinician's abilities to consider and detect genetic disorders so that earlier interventions and optimal outcomes can occur. PMID:17551462

Cogan, Joy D; Phillips, John A

2006-08-01

252

Molecular genetic analysis of single cells.  

PubMed

Preimplantation genetic diagnosis (PGD) has experienced a considerable technical evolution since its first application in the early 1990s. The technology for single-cell genetic analysis has reached an extremely high level of accuracy and enabled the possibility of performing multiple diagnoses from one cell. Diagnosis of a monogenic disease can now be combined with aneuploidy screening, human leukocyte antigen typing, and DNA fingerprinting. New technologies such as microarrays are opening the way for an increasing number of serious genetic defects to be detected in preimplantation embryos. The new PGD techniques will empower patients and clinicians to screen for almost any kind of genetic problem in embryos, with the potential to change completely the manner in which parents approach and manage genetic disease. PMID:22723008

Fiorentino, Francesco

2012-06-21

253

The ethics of using genetic engineering for sex selection.  

PubMed

It is quite likely that parents will soon be able to use genetic engineering to select the sex of their child by directly manipulating the sex of an embryo. Some might think that this method would be a more ethical method of sex selection than present technologies such as preimplantation genetic diagnosis (PGD) because, unlike PGD, it does not need to create and destroy "wrong gendered" embryos. This paper argues that those who object to present technologies on the grounds that the embryo is a person are unlikely to be persuaded by this proposal, though for different reasons. PMID:15681683

Liao, S Matthew

2005-02-01

254

Preimplantation genetic diagnosis: strategies and surprises  

Microsoft Academic Search

Several inherited diseases can now be diagnosed by genetic analysis of single cells biopsied from human eggs and preimplantation embryos following in vitro fertilization (IVF). ‘At risk’ couples can, therefore, have only unaffected embryos replaced in the uterus and avoid the possibility of terminating a pregnancy that might only be diagnosed as affected later in gestation. Single-cell genetic analysis has

Alan H. Handyside; Joy D. A. Delhanty

1997-01-01

255

Translational genetics for diagnosis of human disorders of sex development.  

PubMed

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

Baxter, Ruth M; Vilain, Eric

2013-07-15

256

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

Microsoft Academic Search

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

S. Munne; J. Cohen; J. Grifo

1994-01-01

257

Prenatal diagnosis--principles of diagnostic procedures and genetic counseling.  

PubMed

The frequency of inherited malformations as well as genetic disorders in newborns account for around 3-5%. These frequency is much higher in early stages of pregnancy, because serious malformations and genetic disorders usually lead to spontaneous abortion. Prenatal diagnosis allowed identification of malformations and/or some genetic syndromes in fetuses during the first trimester of pregnancy. Thereafter, taking into account the severity of the disorders the decision should be taken in regard of subsequent course of the pregnancy taking into account a possibilities of treatment, parent's acceptation of a handicapped child but also, in some cases the possibility of termination of the pregnancy. In prenatal testing, both screening and diagnostic procedures are included. Screening procedures such as first and second trimester biochemical and/or ultrasound screening, first trimester combined ultrasound/biochemical screening and integrated screening should be widely offered to pregnant women. However, interpretation of screening results requires awareness of both sensitivity and predictive value of these procedures. In prenatal diagnosis ultrasound/MRI searching as well as genetic procedures are offered to pregnant women. A variety of approaches for genetic prenatal analyses are now available, including preimplantation diagnosis, chorion villi sampling, amniocentesis, fetal blood sampling as well as promising experimental procedures (e.g. fetal cell and DNA isolation from maternal blood). An incredible progress in genetic methods opened new possibilities for valuable genetic diagnosis. Although karyotyping is widely accepted as golden standard, the discussion is ongoing throughout Europe concerning shifting to new genetic techniques which allow obtaining rapid results in prenatal diagnosis of aneuploidy (e.g. RAPID-FISH, MLPA, quantitative PCR). PMID:18292841

Stembalska, Agnieszka; Slezak, Ryszard; Pesz, Karolina; Gil, Justyna; Sasiadek, Maria

2007-01-01

258

Prenatal diagnosis: molecular genetics and cytogenetics  

Microsoft Academic Search

The technologies developed for the Human Genome Project, the recent surge of available DNA sequences resulting from it and the increasing pace of gene discoveries and characterization have all contributed to new technical platforms that have enhanced the spectrum of disorders that can be diagnosed prenatally. The importance of determining the disease-causing mutation or the informativeness of linked genetic markers

Elisabeth Blennow; Magnus Nordenskjöld

2002-01-01

259

A pregnancy following PGD for X-linked dominant [correction of X-linked autosomal dominant] incontinentia pigmenti (Bloch-Sulzberger syndrome): case report.  

PubMed

Incontinentia Pigmenti (Bloch-Sulzberger syndrome) is a rare multisystem, ectodermal disorder associated with dermatological, dental and ocular features, and in <10% of cases, severe neurological deficit. Pedigree review suggests X-linked dominance with lethality in affected males. Presentation in female carriers is variable. Following genetic counselling, a mildly affected female carrier diagnosed in infancy with a de novo mutation was referred for preimplantation sexing, unusually selecting for male gender, with an acceptance of either normality or early miscarriage in an affected male. Following standard in-vitro fertilization and embryo biopsy, fluorescence in situ hybridization (FISH) unambiguously identified two male and two female embryos. A single 8-cell, grade 4 male embryo was replaced. A positive pregnancy test was reported 2 weeks after embryo transfer, although ultrasonography failed to demonstrate a viable pregnancy. Post abortive fetal tissue karyotyping diagnosed a male fetus with trisomy 16. This is an unusual report of preimplantation genetic diagnosis (PGD) being used for selection of males in an X-linked autosomal dominant disorder and demonstrates the value of PGD where amniocentesis or chorion villus sampling followed by abortion is not acceptable to the patient. This case also demonstrates the importance of follow-up prenatal diagnosis. PMID:11098039

Pettigrew, R; Kuo, H C; Scriven, P; Rowell, P; Pal, K; Handyside, A; Braude, P; Ogilvie, C M

2000-12-01

260

Lactose intolerance: diagnosis, genetic, and clinical factors  

PubMed Central

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

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

2012-01-01

261

Structural chromosomal anomalies detected by prenatal genetic diagnosis: our experience.  

PubMed

The prenatal diagnosis is currently widely spread and facilitates the acquiring of important genetic information about the fetus by a rate extremely accelerate and considered without precedent. In this paper, we like to present our experience concerning the genetic diagnosis and counseling offered for pregnancies in which a structural chromosomal aberration was found. The study group is formed by 528 prenatal samples of amniotic fluid and chorionic villi, received by our laboratory from 2006 through October 2012 for cytogenetic diagnosis. The appropriate genetic investigation was selected based on the indications for prenatal diagnosis. The cases with structural chromosomal anomalies and polymorphic variants were analyzed as regard to the maternal age, gestational age, referral indications and type of chromosomal anomaly found. A total number of 21 structural chromosomal anomalies and polymorphic variants were identified in the study group. Out of 21 structural chromosomal anomalies and polymorphic variants, six deletions and microdeletions, four situations with abnormal long "p" arm of acrocentric chromosomes, two duplications, two reciprocal translocations, two inversions, two additions, one Robertsonian translocation associating trisomy 13, one 9q heteromorphism and one complex chromosome rearrangement were noticed. To the best of our knowledge, this is the first Romanian study in which the diagnostic strategies and the management of the prenatal cases with structural rearrangements are presented. The data provided about the diagnosis strategy and the management of the prenatal cases with structural chromosomal anomalies represents a useful tool in genetic counseling of pregnancies diagnosed with rare structural chromosomal anomalies. PMID:23771085

Farca?, Simona; Cri?an, C D; Andreescu, Nicoleta; Stoian, Monica; Motoc, A G M

2013-01-01

262

Candidate Biomarkers for Genetic and Clinicopathological Diagnosis of Endometrial Cancer  

PubMed Central

The recent increase in the frequency of endometrial cancer has emphasized the need for accurate diagnosis and improved treatment. The current diagnosis is still based on conventional pathological indicators, such as clinical stage, tumor differentiation, invasion depth and vascular invasion. However, the genetic mechanisms underlying endometrial cancer have gradually been determined, due to developments in molecular biology, leading to the possibility of new methods of diagnosis and treatment planning. New candidate biomarkers for endometrial cancer include those for molecular epigenetic mutations, such as microRNAs. These biomarkers may permit earlier detection of endometrial cancer and prediction of outcomes and are likely to contribute to future personalized therapy for endometrial cancer.

Banno, Kouji; Nogami, Yuya; Kisu, Iori; Yanokura, Megumi; Umene, Kiyoko; Masuda, Kenta; Kobayashi, Yusuke; Yamagami, Wataru; Susumu, Nobuyuki; Aoki, Daisuke

2013-01-01

263

Candidate biomarkers for genetic and clinicopathological diagnosis of endometrial cancer.  

PubMed

The recent increase in the frequency of endometrial cancer has emphasized the need for accurate diagnosis and improved treatment. The current diagnosis is still based on conventional pathological indicators, such as clinical stage, tumor differentiation, invasion depth and vascular invasion. However, the genetic mechanisms underlying endometrial cancer have gradually been determined, due to developments in molecular biology, leading to the possibility of new methods of diagnosis and treatment planning. New candidate biomarkers for endometrial cancer include those for molecular epigenetic mutations, such as microRNAs. These biomarkers may permit earlier detection of endometrial cancer and prediction of outcomes and are likely to contribute to future personalized therapy for endometrial cancer. PMID:23743825

Banno, Kouji; Nogami, Yuya; Kisu, Iori; Yanokura, Megumi; Umene, Kiyoko; Masuda, Kenta; Kobayashi, Yusuke; Yamagami, Wataru; Susumu, Nobuyuki; Aoki, Daisuke

2013-06-06

264

[Genetic diagnosis of familial dilated cardiomyopathy].  

PubMed

The definition of familial dilated cardiomyopathy (DCM) is clinically based on the presence, in the same family, of at least two members proven as affected. The prevalence of familial forms is about 25-30%. The approach to define the prevalence of familial diseases and to identify asymptomatic subjects is based on a clinical, non-invasive screening of family members of consecutive index patients. Familial DCM is commonly inherited as autosomal dominant trait; less frequently it is autosomal recessive, X-linked or matrilinear. The disease is clinically and genetically heterogeneous. Genes causally linked to this phenotype include dystrophin, dystrophin-associated glycoproteins, actin, desmin, beta-miosin heavy chain, cardiac troponin T, and mitochondrial DNA genes, mostly transfer RNAs. A peculiar phenotype is DCM associated with atrioventricular block, an autosomal dominant disorder that is causally linked to lamin A/C gene defects in a high proportion of cases. Although the knowledge on molecular genetics of DCM is progressively increasing, at present, the number of molecular diagnoses that can be provided to patients is limited to a few X-linked, autosomal dominant and matrilinear DCMs (overall, about 10% of DCMs). The new clinical approach to familial DCM studies, based on the screening of family members, will bring to the cardiologist's attention both patients and relatives, with extension of the clinical evaluation to subjects who are still healthy. On the other hand, molecular genetists will face a complex molecular field, for both high heterogeneity and poor phenotypical specificity. Therefore, interdisciplinary clinical and research projects are especially needed, hopefully coordinated by scientific societies. PMID:12025381

Pasotti, Michele; Repetto, Alessandra; Pisani, Angela; Arbustini, Eloisa

2002-04-01

265

Chronic Pancreatitis: Diagnosis, Classification, and New Genetic Developments  

Microsoft Academic Search

The utilization of recent advances in molecular and genomic technologies and progress in pancreatic imaging techniques provided remarkable insight into genetic, environmental, immunologic, and pathobiological factors leading to chronic pancreatitis. Translation of these advances into clinical practice demands a reassessment of current approaches to diagnosis, classification, and staging. We conclude that an adequate pancreatic biopsy must be the gold standard

Babak Etemad; David C. Whitcomb

2001-01-01

266

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

PubMed Central

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

Hepburn, E R

1996-01-01

267

Hyperinsulinaemic Hypoglycaemia: Genetic Mechanisms, Diagnosis and Management  

PubMed Central

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

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

2012-01-01

268

Genetic diagnosis in pediatric cardiomyopathy: clinical application and research perspectives  

PubMed Central

There has been tremendous growth in the application of genetics to the clinical practice of pediatric cardiomyopathy. The identification of the genetic basis for cardiomyopathies is important for establishing a causal diagnosis, providing definitive identification of at risk family members, and providing cost-effective screening and surveillance. Additional research is needed to better understand the genetic heterogeneity of cardiomyopathy in children, the implications of specific genotypes, the best approach to cardiac surveillance and genetic testing, and the utility of genotyping for individual risk stratification. As the technology for evaluation of the human genome continues to improve, there is an increasing need for assessment of clinical relevance and utility. This is coupled with an ongoing need for education and training of professionals to interpret and implement genomics in a clinical setting.

Ware, Stephanie M.

2011-01-01

269

Analysis using fish of sperm and embryos from two carriers of rare rob(13;21) and rob(15;22) robertsonian translocation undergoing PGD.  

PubMed

The majority of fluorescence in situ hybridization (FISH) studies on the meiotic segregation of Robertsonian translocations focus on the most common types, rob(13; 14) and rob(14; 21). Here we report the first study for carriers of rare Robertsonian translocations rob(13; 21) and rob(15; 22) combining analysis of meiotic segregation in sperm and blastomeres following pre-implantation genetic diagnosis (PGD). Dual-colour FISH was applied to nuclei from spermatozoa and blastomeres from PGD embryos using two subterminal contig probes for each translocation, and a second round with probes for chromosomes 16 and 18. Patient 1 had a rob(13; 21) and patient 2 had a rob(15; 22), and 86.3% and 87.5% of gametes respectively were consistent with meiotic segregation resulting in a normal or balanced chromosome complement. Analysis of embryos showed that for patient 1 and 2 respectively, 25% and 46% were balanced, and of the unbalanced embryos, 50% and 31% were mosaic or chaotic. Our patients with a rob(13; 21) and rob(15; 22) were found to have a similar meiotic segregation pattern to that for male carriers of the common Robertsonian translocations. The observed rate in unbalanced embryos being mosaic or chaotic may result in an increased risk of chromosomal abnormalities. Our results may help to improve the genetic counseling for carriers of rare Robertsonian translocations. PMID:22406402

Bernicot, Izabel; Schneider, Anouck; Mace, Alexandra; Hamamah, Samir; Hedon, Bernard; Pellestor, Franck; Anahory, Tal

2012-02-22

270

Role of genetics in the diagnosis and treatment of epilepsy.  

PubMed

Epilepsy is a heterogeneous group of multifactorial diseases, the vast majority determined by interactions between many genes and environmental factors; however, there are rare epilepsy syndromes that can be caused by a single gene mutation and are inherited according to classical mendelian genetic principles. Finding disease-causing genetic mutations in epilepsy has provided new opportunities for aiding diagnosis and developing therapies. Thus, the discovery of KCNQ2 mutations in benign familial neonatal convulsions, SCN1A mutations in severe myoclonic epilepsy of infancy and in generalized epilepsy with febrile seizures plus, and CHRA4 and CHRB2 mutations in autosomal-dominant nocturnal frontal lobe epilepsy, has led to the establishment of epilepsy as a disorder of ion channel function and, furthermore, has led to the introduction of genetic tests that are available clinically to aid in diagnosis and treatment. At the present time, clinical use of genetic testing in epilepsy is greatest in suspected cases of severe myoclonic epilepsy of infancy, generalized epilepsy with febrile seizures plus, atypical cases of benign familial neonatal convulsions and 'occult' cases of autosomal-dominant nocturnal frontal lobe epilepsy without a family history. Overall, clinical use is limited by the low number of documented disease-associated mutations and the uncertain clinical significance of many test results. Further elucidation of the relationship between gene mutations and channel function will add value to genetic testing in the future, as will better characterization of the association between gene mutations and clinical phenotypes. PMID:17181426

Ferraro, Thomas N; Dlugos, Dennis J; Buono, Russell J

2006-12-01

271

Prospect of preimplantation genetic diagnosis for heritable mitochondrial DNA diseases  

Microsoft Academic Search

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

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

2003-01-01

272

[Genetic diagnosis and molecular pathology of inherited neuropathy].  

PubMed

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

Takashima, Hiroshi

2012-01-01

273

Molecular diagnosis of genetic iron-overload disorders.  

PubMed

Genetic iron overload has long been confined to the picture of classical hemochromatosis related to the HFE C282Y mutation (type 1 hemochromatosis). C282Y homozygosity affects approximately three people out of 1000 of the Caucasian population, representing one of the most frequent genetic predispositions. It has, however, rapidly become clear that the HFE C282Y mutation is not the sole culprit in genetic iron overload. Several novel mutations in HFE and other genes have been discovered and related to various entities, which are now known as types 2, 3 and 4 hemochromatosis. These diseases are far less frequent than the classical type 1 hemochromatosis but, by contrast, are not limited to the Caucasian population. Molecular diagnosis obviously plays a key role in the diagnostic strategy. In the future, it will undoubtedly enable not only identification of new diagnostic markers, but also provide potential molecular targets for pathophysiologically based innovative therapeutic approaches. PMID:20843199

Brissot, Pierre; Bardou-Jacquet, Edouard; Troadec, Marie-Bérengère; Mosser, Annick; Island, Marie-Laure; Detivaud, Lénaïck; Loréal, Olivier; Jouanolle, Anne-Marie

2010-09-01

274

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

275

Single cell co-amplification of polymorphic markers for the indirect preimplantation genetic diagnosis of hemophilia A, X-linked adrenoleukodystrophy, X-linked hydrocephalus and incontinentia pigmenti loci on Xq28.  

PubMed

Preimplantation genetic diagnosis (PGD) first consisted of the selection of female embryos for patients at risk of transmitting X-linked recessive diseases. Advances in molecular biology now allow the specific diagnosis of almost any Mendelian disease. For families with an identified X-linked recessive disease-causing mutation, non-specific diagnosis by sex identification can be considered as a sub-standard method, since it involves the unnecessary disposal of healthy male embryos and reduces success rate by diminishing the pool of embryos eligible for transfer. The most telomeric part of the X-chromosome long arm is a highly gene-rich region encompassing disease genes such as haemophilia A, X-linked adrenoleukodystrophy, X-linked hydrocephalus and incontinentia pigmenti. We developed five single-cell triplex amplification protocols with microsatellite markers DXS1073, DXS9901 (BGN), G6PD, DXS1108, DXS8087 and F8C-IVS13 located in this Xq terminal region. These tests allow the diagnosis of all diseases previously mentioned providing that the genetic material allowing the identification of the morbid allele can be obtained. The choice of the microsatellite set to use depends on the localisation of the gene responsible for the diagnosed pathology and on the informativity of the markers in particular families. Single-cell amplification efficiency was assessed on single lymphocytes. Amplification rate of the different markers ranged from 89-97% with an allele drop out rate of 2-19%. So far PGD has been carried out for three carrier females at risk of transmitting X-linked adrenoleukodystrophy, X-linked hydrocephalus and hemophilia A. The latter one is now pregnant. PMID:14673643

Gigarel, Nadine; Frydman, Nelly; Burlet, Philippe; Kerbrat, Violaine; Steffann, Julie; Frydman, René; Munnich, Arnold; Ray, Pierre F

2003-12-12

276

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

277

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

278

Critical Issues for Dentistry: PGD Program Directors Respond  

Microsoft Academic Search

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

Kathryn A. Atchison; Susan E. Cheffetz

279

Multiple displacement amplification improves PGD for fragile X syndrome  

Microsoft Academic Search

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

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

2006-01-01

280

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

Microsoft Academic Search

Deleterious mutations in the BRCA1\\/BRCA2 genes elevate lifetime risk of breast and ovarian cancer. Each child of a mutation-positive parent has a 50% chance of inheriting it. Preimplantation genetic diagnosis (PGD) permits prospective parents to avoid the birth of a BRCA-mutation-positive child, introducing predictability into a process historically defined by chance. This investigation explored how BRCA1\\/2 mutation carriers understand genetic

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

2012-01-01

281

Molecular strategies for pre-implantation genetic diagnosis of single gene and chromosomal disorders.  

PubMed

Pre-implantation genetic diagnosis is used to analyse pre-implantation stage embryos or oocytes for genetic defects, generally for severe Mendelian disorders and chromosome abnormalities. New but controversial indications for pre-implantation genetic diagnosis include identifying human leukocyte antigen compatible embryos suitable as donor, sex selection and adult-onset disorders, particularly cancer. Pre-implantation genetic screening is a variant of pre-implantation genetic diagnosis to improve outcomes of in-vitro fertilisation. Array comparative genomic hybridisation is replacing fluorescence in-situ hybridisation for aneuploidy screening. Besides technical advancement of array platform, the success of pre-implantation genetic screening is strongly related to the embryonic biological nature of chromosomal mosaicism. Having been applied for more than 20 years, pre-implantation genetic diagnosis is recognised as an important alternative to prenatal diagnosis. Diagnosis from a single cell, however, remains a technically challenging procedure, and the risk of misdiagnosis cannot be eliminated. PMID:22858134

Jiang, Boran; Tan, Arnold S C; Chong, Samuel S

2012-08-01

282

Genetic counseling and "molecular" prenatal diagnosis of holoprosencephaly (HPE).  

PubMed

Holoprosencephaly (HPE) is a structural anomaly of the developing brain in which the forebrain fails to divide into two separate hemispheres and ventricles. The poor prognosis in the most severe forms justifies the importance of genetic counseling in affected families. The genetic counseling requires a thorough clinical approach given the extreme variability of phenotype and etiology. The karyotype is an essential diagnostic tool. Since mutations in the four major genes (SHH, ZIC2, SIX3, and TGIF) have been identified in HPE patients, molecular study is performed routinely in nonsyndromic HPE. New molecular tools, such as array-CGH analysis, are now part of the diagnostic process. Prenatal diagnosis is based primarily on fetal imaging, but "molecular" prenatal diagnosis can be performed if a mutation has been previously identified in a proband. Interpretations of molecular diagnosis must be given with caution, given the lack of strict genotype-phenotype correlation, and should be offered in addition to fetal imaging, using ultrasound followed by fetal MRI. We report on our experience of 15 molecular prenatal diagnoses from chorionic villi or amniotic fluid sampling. In eight instances, we were able to reassure the parents after taking into account the absence of the mutation in the fetus, previously identified before in a parent and/or a proband. Fetal RMI was normal later in pregnancy, and no child had medical problems after birth. The mutation was found in the seven other cases: four children were born, either without brain malformation and asymptomatic, or had a less severe form than the index case. PMID:20104616

Mercier, Sandra; Dubourg, Christèle; Belleguic, Marion; Pasquier, Laurent; Loget, Philippe; Lucas, Josette; Bendavid, Claude; Odent, Sylvie

2010-02-15

283

[Diagnosis of the peripheral hereditary neuropathies and its molecular genetics].  

PubMed

Peripheral neuropathies include a wide range of pathological disorders characterized by damage of peripheral nerves. Among them, peripheral hereditary neuropathies are a group of frequent illnesses and early evolution. They have been named hereditary motor and sensory neuropathy (HMSN) or peripheral hereditary neuropathies type Charcot-Marie-Tooth (CMT). The most frequent types are CMT1, CMT2 and CMTX. Approximately 70% of the cases correspond to subtype CMT1A, associated with tandem duplication of a 1.5 Mb DNA fragment on chromosome 17p11.2-p12 that codifies the peripheral myelin protein PMP22. So far, there five different types of CMT (1,2,3,4,X) with approximately 32 subtypes, associated with more than 30 genes. Have been reported genetic heterogeneity and expression variability of the illness makes it necessary to carry on diagnostic strategies that integrate clinical study for determining genetic clinical history, family history, complete physical exploration, muscular strength, physical deformities, reflexes and sensitivity, and molecular studies allow detection of different types of mutations and help establish a correct diagnosis and an adequate genetic counseling. PMID:18979992

Hernández-Zamora, Edgar; Arenas-Sordo, María de la Luz

284

What is the Impact of Genetic Counseling and Prenatal Diagnosis in Genetic Diseases Prevention in an Arab Muslim Population?  

Microsoft Academic Search

Genetic counseling remains the best and the most efficient action for genetic diseases prevention. Based on families' education, and sometimes followed by prenatal or preimplantation diagnosis, genetic counseling is relevant by reducing the incidence of hereditary and congenital disorders. The development of medical care, the accumulation of laboratory techniques and the legality of pregnancy termination will help largely to decrease

Habiba Chaabouni Bouhamed; Myriam Chaabouni; Imen Chelly; Ines Ouertani; Lamia Ben Jemaa; Ridha Mrad; Faouzi Maazoul

285

Improving the reliability of heuristic multiple fault diagnosis via the EC-based Genetic Algorithm  

Microsoft Academic Search

Engineered Conditioning (EC) is a Genetic Algorithm operator that works together with the typical genetic algorithm operators: mate selection, crossover, and mutation, in order to improve convergence toward an optimal multiple fault diagnosis. When incorporated within a typical genetic algorithm, the resulting hybrid scheme produces improved reliability by exploiting the global nature of the genetic algorithm as well as “local”

Walter D. Potter; John A. Miller; Bruce E. Tonn; Ravi V. Gandham; Chito N. Lapena

1992-01-01

286

Three-dimensional partial zona dissection for preimplantation genetic diagnosis and assisted hatching  

Microsoft Academic Search

Objective: To develop a new approach to partial zona dissection of oocytes and embryos for facilitating preimplantation genetic sampling and assisted hatching.Design: Controlled clinical study.Setting: Preimplantation genetic diagnosis and IVF program, Reproductive Genetics Institute\\/IVF Illinois, Chicago, Illinois.Patient(s): Three hundred forty patients undergoing IVF in whom preimplantation genetic diagnosis or assisted hatching was required.Intervention(s): Three-dimensional partial zona dissection and conventional partial

Jeanine Cieslak; Victor Ivakhnenko; Georg Wolf; Svetlana Sheleg; Yury Verlinsky

1999-01-01

287

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

PubMed

Hereditary forms of colorectal cancer, as is the case with virtually all forms of hereditary cancer, show extensive phenotypic and genotypic heterogeneity, a phenomenon discussed throughout this special issue of Familial Cancer. Clearly, the family physician, oncology specialist, genetic counselor, and cancer geneticist must know fully the complexity of hereditary cancer syndromes, their differential diagnosis, in order to establish a diagnosis, direct highly-targeted surveillance and management, and then be able to communicate effectively with the molecular geneticist so that an at-risk patient's DNA can be tested in accord with the syndrome of concern. Thus, a family with features of the Lynch syndrome will merit microsatellite instability testing, consideration for immunohistochemistry evaluation, and mismatch repair gene testing, while, in contrast, a patient with FAP will require APC testing. However, other germline mutations, yet to be identified, may be important should testing for these mutations prove to be absent and, therein, unrewarding to the patient. Nevertheless, our position is that if the patient's family history is consistent with one of these syndromes, but a mutation is not found in the family, we still recommend the same surveillance and management strategies for patients from families with an established cancer-causing germline mutation. Our purpose in this paper is to provide a concise coverage of the major hereditary colorectal cancer syndromes, to discuss genetic counseling, molecular genetic evaluation, highly targeted surveillance and management, so that cancer control can be maximized for these high hereditary cancer risk patients. PMID:17999161

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

2007-11-13

288

Preimplantation genetic diagnosis for gender selection for family balancing: a view from India.  

PubMed

The use of PGD for sex selection arouses considerable debate, especially in countries like India that have a marked cultural preference for boys. It is argued that using PGD for sex selection is a treatment option that can be ethically offered to couples who desire to use this technology to plan their families. PMID:12470342

Malpani, A; Malpani, A

289

Preimplantation genetic diagnosis for gender selection for family balancing: a view from India  

Microsoft Academic Search

The use of PGD for sex selection arouses considerable debate, especially in countries like India that have a marked cultural preference for boys. It is argued that using PGD for sex selection is a treatment option that can be ethically offered to couples who desire to use this technology to plan their families.

A Malpani

2002-01-01

290

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

Microsoft Academic Search

The current state of molecular diagnosis of some common genetic diseases, including cystic fibrosis, Duchenne muscular dystrophy, haemophilia A and B, phenylketonuria, and thalassaemia, in Russia and elsewhere in the former USSR is reviewed. Data on carrier detection and prenatal diagnosis are presented and some objective problems and obstacles hampering efficient molecular diagnosis in Russia are discussed. The necessity for

V S Baranov

1993-01-01

291

Real-time PCR for prenatal and preimplantation genetic diagnosis of monogenic diseases  

Microsoft Academic Search

The provision of prenatal diagnosis requires the highest standards in laboratory practice to ensure an accurate result. In preimplantation genetic diagnosis protocols additionally have to address the need to achieve an accurate result from 1 to 2 cells within a limited time. Emerging protocols of “non-invasive” prenatal diagnosis, which are based on analysis of free fetal DNA in the circulation

Joanne Traeger-Synodinos

2006-01-01

292

PGD training and its impact on general dentist practice patterns.  

PubMed

This study compares the practice patterns of general dentists with and without formal advanced training in AGED or GPR programs. The UCLA School of Dentistry surveyed a random selection of dentists from graduating years 1989, 1993, and 1997 as part of a Health Resources Services Administration (HRSA)-supported evaluation of the impact of federal funding on postgraduate general dentistry (PGD) programs. Using a sample drawn by the American Dental Association (ADA), 6,725 dentists were surveyed about their practice, advanced training, patients served, and services provided. Of the 2,029 dentists (30 percent) who responded, 49 percent were practicing dentists with no formal advanced training in general dentistry or one of the eight ADA specialties; 7 percent had Advanced Education in General Dentistry (AEGD) experience; 20 percent trained in a General Practice Residency (GPR); and 24 percent were specialists. Additionally, 7 percent of respondents had PGD training and a clinical specialty. GPR-trained dentists were significantly more likely to be on a hospital staff and to treat medically compromised patients even after ten years of practice. PGD dentists were less likely to seek specialty training. Major reasons for seeking PGD training were increasing treatment speed, learning to treat medically compromised patients, and wanting hospital experience. Primary reasons for not selecting training were starting a practice and having a great practice opportunity. Our conclusion is that PGD training has an enduring impact on practice patterns and improves access to dental care for underserved populations. PMID:12521061

Atchison, Kathryn A; Mito, Ronald S; Rosenberg, Dara Jean; Lefever, Karen H; Lin, Sylvia; Engelhardt, Rita

2002-12-01

293

Impacts of massively parallel sequencing for genetic diagnosis of neuromuscular disorders.  

PubMed

Neuromuscular disorders (NMD) such as neuropathy or myopathy are rare and often severe inherited disorders, affecting muscle and/or nerves with neonatal, childhood or adulthood onset, with considerable burden for the patients, their families and public health systems. Genetic and clinical heterogeneity, unspecific clinical features, unidentified genes and the implication of large and/or several genes requiring complementary methods are the main drawbacks in routine molecular diagnosis, leading to increased turnaround time and delay in the molecular validation of the diagnosis. The application of massively parallel sequencing, also called next generation sequencing, as a routine diagnostic strategy could lead to a rapid screening and fast identification of mutations in rare genetic disorders like NMD. This review aims to summarize and to discuss recent advances in the genetic diagnosis of neuromuscular disorders, and more generally monogenic diseases, fostered by massively parallel sequencing. We remind the challenges and benefit of obtaining an accurate genetic diagnosis, introduce the massively parallel sequencing technology and its novel applications in diagnosis of patients, prenatal diagnosis and carrier detection, and discuss the limitations and necessary improvements. Massively parallel sequencing synergizes with clinical and pathological investigations into an integrated diagnosis approach. Clinicians and pathologists are crucial in patient selection and interpretation of data, and persons trained in data management and analysis need to be integrated to the diagnosis pipeline. Massively parallel sequencing for mutation identification is expected to greatly improve diagnosis, genetic counseling and patient management. PMID:23224362

Vasli, Nasim; Laporte, Jocelyn

2012-12-07

294

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.

2012-01-01

295

Fluorescent PCR: A new technique for PGD of sex and single-gene defects  

Microsoft Academic Search

Background: For single-cell diagnosis, particularly preimplantation genetic diagnosis to be successful four main criteria must be achieved: sensitivity, reliability, accuracy, and identification\\/elimination of contamination.

Ian Findlay; Philip Quirke; June Hall; Anthony Rutherford

1996-01-01

296

Reduction in signal overlap results in increased FISH efficiency: Implications for preimplantation genetic diagnosis  

Microsoft Academic Search

Background: In the absence of mosaicism, one of the problems of preimplantation genetic diagnosis with FISH is the occurrence of false-negative hybridization results. It has been hypothesized that missing signals are produced by spatial overlap of signals.

Santiago Munné; Theresa Dailey; Michelle Finkelstein; Heinz-Ulrich G. Weier

1996-01-01

297

Genetics on stage: public engagement in health policy development on preimplantation genetic diagnosis.  

PubMed

Arts-based approaches to public engagement offer unique advantages over traditional methods of consultation. Here we describe and assess our use of theatre as a method of public engagement in the development of health policy on preimplantation genetic diagnosis, a controversial method for selecting the genetic characteristics of embryos created through in vitro fertilization. Funding from the Canadian Institutes for Health Research and Health Canada supported 16 performances of the play Orchids in Vancouver, Toronto, and Montréal and post-performance discussion in English and French (with Hubert Doucet) in 2005. A total of 741 individuals attended. The methods used to assess audience engagement and elicit policy-relevant dialogue included in-theatre observation of audience responses, moderated post-performance large audience discussion and focus groups, audience feedback forms and researcher fieldnotes. Emphasizing process and context over emerging outcomes, we reflect on the distinctive contributions of theatre in stimulating public engagement and the need to utilize multiple methods to adequately assess these contributions. We suggest continued dialogue about the possible uses of theatre in health policy development and conclude that greater clarity is needed with regard to citizens' (as well as specific stakeholders, policy makers' and sponsors') desired outcomes if there is to be a suitably nuanced and reflexive basis for assessing the effectiveness of various strategies for public engagement. PMID:19233530

Cox, Susan M; Kazubowski-Houston, Magdalena; Nisker, Jeff

2009-02-21

298

Personalized medicine: genetic diagnosis for inherited cardiomyopathies/channelopathies.  

PubMed

Major advances in the field of molecular genetics have expanded our ability to identify genetic substrates underlying the pathogenesis of various disorders that follow Mendelian inheritance patterns. Included among these disorders are the potentially lethal and heritable channelopathies and cardiomyopathies for which the underlying genetic basis has been identified and is now better understood. Clinical and genetic heterogeneity are hallmark features of these disorders, with thousands of gene mutations being implicated within these divergent cardiovascular diseases. Genetic testing for several of these heritable channelopathies and cardiomyopathies has matured from discovery to research-based genetic testing to clinically/commercially available diagnostic tests. The purpose of this review is to provide the reader with a basic understanding of human medical genetics and genetic testing in the context of cardiovascular diseases of the heart. We review the state of clinical genetic testing for the more common channelopathies and cardiomyopathies, discuss some of the pertinent issues that arise from genetic testing, and discuss the future of personalized medicine in cardiovascular disease. Full English text available from:www.revespcardiol.org/en. PMID:23484907

Ackerman, Michael J; Marcou, Cherisse A; Tester, David J

2013-02-26

299

A Hybrid Genetic-Fuzzy Expert System for Effective Heart Disease Diagnosis  

Microsoft Academic Search

\\u000a This paper presents a genetic algorithm (GA)-based fuzzy logic approach for computer aided disease diagnosis scheme. The aim\\u000a is to design a fuzzy expert system for heart disease diagnosis. The designed system is based on Cleveland Heart Disease database.\\u000a Originally there were thirteen attributes involved in predicting the heart disease. In this work genetic algorithm is used\\u000a to determine the

E. P. Ephzibah

300

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

301

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

302

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

303

PGD2-CRTH2 pathway promotes tubulointerstitial fibrosis.  

PubMed

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

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

2012-09-20

304

PGD2-CRTH2 Pathway Promotes Tubulointerstitial Fibrosis  

PubMed Central

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

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

2012-01-01

305

PGD for dystrophin gene deletions using fluorescence in situ hybridization.  

PubMed

Duchenne muscular dystrophy and Becker muscular dystrophy (DMD and BMD) are caused by mutations in the dystrophin gene (Xp21). In two-thirds of DMD/BMD cases, the mutation is a large deletion of one or several exons. We have established PGD for DMD/BMD using interphase fluorescence in situ hybridization (FISH) analysis on single nuclei from blastomeres for the detection of deletions of specific exons in the dystrophin gene. We performed PGD for two carrier females; one had a deletion of exons 45-50 (DMD), and the other had a deletion of exons 45-48 (BMD). An exon 45-specific probe was used in combination with probes for the X and Y centromeres. Using this straightforward approach, we can distinguish affected and unaffected male embryos as well as carrier female and normal female embryos. Three cycles were performed for each patient, which resulted in a pregnancy and the birth of a healthy girl. To the best of our knowledge, this approach for PGD has not been previously reported. The use of interphase FISH is an attractive alternative to sexing or PCR-based mutation detection for PGD patients with known deletions of the dystrophin gene. PMID:16608904

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

2006-04-11

306

Application of genetic algorithms to fault diagnosis in nuclear power plants  

Microsoft Academic Search

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

Zhou Yangping; Zhao Bingquan; Wu DongXin

2000-01-01

307

Male and female meiotic behaviour of an intrachromosomal insertion determined by preimplantation genetic diagnosis  

Microsoft Academic Search

BACKGROUND: Two related family members, a female and a male balanced carrier of an intrachromosomal insertion on chromosome 7 were referred to our centre for preimplantation genetic diagnosis. This presented a rare opportunity to investigate the behaviour of the insertion chromosome during meiosis in two related carriers. The aim of this study was to carry out a detailed genetic analysis

Leoni Xanthopoulou; Anna Mantzouratou; Anastasia Mania; Suzanne Cawood; Alpesh Doshi; Domenico M Ranieri; Joy DA Delhanty

2010-01-01

308

Investigation of Genetic Algorithms for Computer-Aided Diagnosis.  

National Technical Information Service (NTIS)

Computer-aided diagnosis has the potential of substantially increasing diagnostic accuracy in mammography. Using a computer to double-check a radiologist's findings is becoming more popular and more important as the public learns that the best defense aga...

M. A. Kupinski

2000-01-01

309

Investigation of Genetic Algorithms for Computer-Aided Diagnosis.  

National Technical Information Service (NTIS)

Computer-aided diagnosis has the potential of substantially increasing diagnostic accuracy in mammography. Using a computer to double-check a radiologist's findings is becoming more popular and more important as the public learns that the best defense aga...

M. A. Kupinski

1999-01-01

310

Investigation of Genetic Algorithms for Computer-Aided Diagnosis.  

National Technical Information Service (NTIS)

Computer-aided diagnosis has the potential of substantially increasing diagnostic accuracy in mammography. Using a computer to double-check a radiologist's findings is becoming more popular and more important as the public learns that the best defense aga...

M. A. Kupinski

1998-01-01

311

A Case Report of Fanconi Anemia Diagnosed by Genetic Testing Followed by Prenatal Diagnosis  

PubMed Central

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

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

2012-01-01

312

Genetic information in the diagnosis and treatment of hypertension  

Microsoft Academic Search

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

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

2006-01-01

313

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

PubMed

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, V A; Lee, H; Sánchez, F J; Délot, E C; Sandberg, D E; Grody, W W; Nelson, S F; Vilain, E

2012-05-01

314

A genetic algorithm approach to multi-disorder diagnosis  

Microsoft Academic Search

One of the common limitations of expert systems for medical diagnosis is that they make an implicit assumption that multiple disorders do not co-occur in a single patient. The need for this simplifying assumption stems from the fact that finding minimal sets of disorders that cover all symptoms for a given patient is generally computationally intractable (NP-hard). In this paper,

Staal A. Vinterbo; Lucila Ohno-machado

2000-01-01

315

Centrifuge modeling of PGD response of buried pipe  

NASA Astrophysics Data System (ADS)

A new centrifuge based method for determining the response of continuous buried pipe to PGD is presented. The physical characteristics of the RPI's 100 g-ton geotechnical centrifuge and the current lifeline experiment split-box are described: The split-box contains the model pipeline and surrounding soil and is manufactured such that half can be offset, in flight, simulating PGD. In addition, governing similitude relations which allow one to determine the physical characteristics, (diameter, wall thickness and material modulus of elasticity) of the model pipeline are presented. Finally, recorded strains induced in two buried pipes with prototype diameters of 0.63 m and 0.95 m (24 and 36 inch) subject to 0.6 and 2.0 meters (2 and 6 feet) of full scale fault offsets and presented and compared to corresponding FE results.

O'Rourke, Michael; Gadicherla, Vikram; Abdoun, Tarek

2005-06-01

316

Hereditary deafness: lessons for developmental studies and genetic diagnosis  

Microsoft Academic Search

Hereditary deafness is highly heterogeneous genetically, with over 100 loci so far identified. Routine diagnostic mutation screening can be done only when a candidate gene has been identified, and preferably a candidate mutation. For syndromic forms of hearing loss it is often possible to predict the gene involved. Non-syndromic loss is much more intractable to diagnostic mutation screening because of

Andrew P. Read

2000-01-01

317

Phosphogluconat-Dehydrogenase (PGD). Stichprobe aus der Berliner Bevölkerung  

Microsoft Academic Search

Summary The findings during a study of human red cell phosphogluconate dehydrogenase polymorphism in the population of West-Berlin are reported. Application of a discontinuous citrate-phosphate buffer system makes possible the combined detection of PGD- and AK-phenotypes in a single electrophoretical run. The results in the Berlin-survey supports the hypothesis of two allele genes with codominant autosomal transmission. The significance in

M. Smerling

1971-01-01

318

PGD Training and Its Impact on General Dentist Practice Patterns  

Microsoft Academic Search

Abstract: This study compares,the practice patterns of general dentists with and without formal advanced,training in AGED or GPR programs. The UCLA School of Dentistry surveyed a random selection of dentists from graduating years 1989, 1993, and 1997 as part of a Health Resources Services Administration (HRSA)-supportedevaluation of the impact of federal funding on postgraduate general dentistry (PGD) programs. Using a

Kathryn A. Atchison; Fds Rcs; Dara Jean Rosenberg; Sylvia Lin; Rita Engelhardt

319

PGD for dystrophin gene deletions using fluorescence in situ hybridization  

Microsoft Academic Search

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

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

2006-01-01

320

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

PubMed

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

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

2011-08-03

321

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

PubMed Central

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

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

2012-01-01

322

Prenatal diagnosis of genetic syndromes may be facilitated by serendipitous findings at fetal blood sampling.  

PubMed

Two women without a specific risk had fetuses with multiple malformations diagnosed by ultrasound; extensive biochemical investigations on fetal blood revealed clues which would have allowed the correct diagnosis of a genetic condition: Pallister-Killian syndrome in one with increased fetal LDH, and Smith-Lemli-Opitz type II syndrome in the other with low fetal cholesterolaemia. When compared with chorionic villus sampling and amniocentesis, rapid karyotyping in women with multiple fetal malformations by fetal blood sampling allows the collection of additional data which may lead to the diagnosis of specific genetic syndromes. PMID:9742573

Lalatta, F; Salmona, S; Fogliani, R; Rizzuti, T; Nicolini, U

1998-08-01

323

High-efficiency derivation of human embryonic stem cell lines following pre-implantation genetic diagnosis  

Microsoft Academic Search

Pre-implantation genetic diagnosis allows the characterisation of embryos that carry a gene responsible for a severe monogenic\\u000a disease and to transfer to the mother’s uterus only the unaffected one(s). The genetically affected embryos can be used to\\u000a establish human embryonic stem cell (hESC) lines. We are currently establishing a cell bank of ESC lines carrying specific\\u000a disease-causing mutant genes. These

Philippe Tropel; Johana Tournois; Julien Côme; Christine Varela; Céline Moutou; Pascal Fragner; Michel Cailleret; Yacine Laâbi; Marc Peschanski; Stéphane Viville

2010-01-01

324

[A new genetic diagnosis of familiar gastrointestinal stromal tumour].  

PubMed

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the gastrointestinal tract. Familial GIST with autosomal dominant inheritance and mutation in c-KIT or PDGFR-?, are rare and characterized by multiple GIST, relatively young age at diagnosis and hyperplasia of the interstitial cells of Cajal. Around twenty families with germ line mutations in c-KIT and three families with mutations in PDGFR-? have previously been published. In this case we present a family with familial GIST and mutation in c-KIT. PMID:22640790

Wadt, Karin; Andersen, Mette Klarskov; Hansen, Thomas V O; Gerdes, Anne-Marie

2012-05-21

325

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

PubMed

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

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

2013-06-22

326

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.

Ramirez, Hugo; Reina, Ramses; Amorena, Beatriz; de Andres, Damian; Martinez, Humberto A.

2013-01-01

327

The second PGD 2 receptor CRTH2: structure, properties, and functions in leukocytes  

Microsoft Academic Search

Prostaglandin (PG) D2 plays a broad range of physiological and pathophysiological functions. Until just a few years ago, it was thought that most of the biological actions of PGD2 are mediated via the classical PGD2 receptor DP. Recently, we identified a second PGD2 receptor, chemoattractant receptor-homologous molecule expressed on T helper (Th)2 cells (CRTH2), with different functions relative to DP.

Kinya Nagata; Hiroyuki Hirai

2003-01-01

328

Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies  

Microsoft Academic Search

This article summarizes the present knowledge, recent developments, and common pitfalls in the diagnosis, classification, and genetics of hyperphenylalaninemia, including tetrahydrobiopterin (BH4) deficiency. It is a product of the recent workshop organized by the European Phenylketonuria Group in March 2011 in Lisbon, Portugal. Results of the workshop demonstrate that following newborn screening for phenylketonuria (PKU), using tandem mass-spectrometry, every newborn

Nenad Blau; Julia B. Hennermann; Ulrich Langenbeck; Uta Lichter-Konecki

329

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

Microsoft Academic Search

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

Jochen Reiss; David N. Cooper

1990-01-01

330

Selecting critical clinical features for heart diseases diagnosis with a real-coded genetic algorithm  

Microsoft Academic Search

In clinic, normally a lot of diagnostic features are recorded from a patient for a certain disease. It will be beneficial for the prompt and correct diagnosis of the disease by selecting the important and relevant features and discarding those irrelevant and redundant ones. In this paper, a real-coded genetic algorithm (GA)-based system is proposed to select the critical clinical

Hongmei Yan; Jun Zheng; Yingtao Jiang; Chenglin Peng; Shouzhong Xiao

2008-01-01

331

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

332

Advantages of Day 4 Embryo Transfer in Patients Undergoing Preimplantation Genetic Diagnosis of Aneuploidy  

Microsoft Academic Search

Purpose:Following preimplantation genetic diagnosis of aneuploidy, embryo transfer was executed on day 4, with the aim of providing more time for expanding from six to nine the number of diagnosed chromosomes per single cell (Group 2; 45 cycles). The results obtained were compared to those derived from conventional day 3 transfer (Group 1; 71 cycles).

Luca Gianaroli; M. Cristina Magli; Santiago Munné; Daniela Fortini; Anna P. Ferraretti

1999-01-01

333

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

Microsoft Academic Search

Preimplantation genetic diagnosis (PIGD) goes some way to meeting the clinical, psychological and ethical problems of antenatal testing. We should guard, however, against the assumption that PIGD is the answer to all our problems. It also presents some new problems and leaves some old problems untouched. This paper will provide an overview of how PIGD meets some of the old

H Draper; R Chadwick

1999-01-01

334

Optimization of fuzzy rules by Muilti-objective genetic algorithm in avionic fault diagnosis system  

Microsoft Academic Search

The fuzzy rule sets, which have been widely used in avionic fault diagnosis system, have considerable redundancy that leads to time-consuming faults location process. In this paper, to reduce the redundant rules, a multiple objective genetic algorithm, MOGAII, is used to optimize a fuzzy rule set. The optimization problem with two objectives, the maximization diagnostic capability of the system and

Zhang Jing; Gao Qiang; Huang ZhiGang; Huang ZhaoTing

2009-01-01

335

On the parallelization and optimization of the genetic-based ANN classifier for the diagnosis of students with learning disabilities  

Microsoft Academic Search

Diagnosis of students with learning disabilities has long been a difficult issue as it requires extensive man power and takes a long time. Through genetic algorithm based feature selection method and genetic based parameters optimization, artificial neural network (ANN) classifier has proven to be a good predictor to the diagnosis of students with learning disabilities. In this study, we keep

Tung-Kuang Wu; Shian-Chang Huang; Y.-L. Lin; H. Chang; Ying-Ru Meng

2010-01-01

336

Hyperinsulinaemic hypoglycaemia:genetic mechanisms, diagnosis and management.  

PubMed

Hyperinsulinaemic hypoglycaemia (HH) is characterized by unregulated insulin secretion from pancreatic ?-cells. Untreated hypoglycaemia in infants can lead to seizures, developmental delay, and subsequent permanent brain injury. Early identification and meticulous managementof these patients is vital to prevent neurological insult. Mutations in eight different genes (ABCC8, KCNJ11, GLUD1, CGK, HADH, SLC16A1, HNF4A and UCP2) have been identified to date in patients with congenital forms of hyperinsulinism (CHI). The most severe forms of CHI are due to mutations in ABCC8 and KCJN11, which encode the two components of pancreatic ?-cell ATP-sensitive potassium channel. Recent advancement in understanding the genetic aetiology, histological characterisation into focal and diffuse variety combined with improved imaging (such as fluorine 18 L-3, 4-dihydroxyphenylalanine positron emission tomography 18F-DOPA-PET scanning) and laparoscopic surgical techniques have greatly improved management. In adults, HH can be due to an insulinoma, pancreatogenous hypoglycaemic syndrome, post gastric-bypass surgery for morbid obesity as well as to mutations in insulin receptor gene. This review provides an overview of the molecular basis of CHI and outlines the clinical presentation, diagnostic criteria, and management of these patients. PMID:23032149

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

2012-10-02

337

Genetic diagnosis by whole exome capture and massively parallel DNA sequencing  

PubMed Central

Protein coding genes constitute only approximately 1% of the human genome but harbor 85% of the mutations with large effects on disease-related traits. Therefore, efficient strategies for selectively sequencing complete coding regions (i.e., “whole exome”) have the potential to contribute to the understanding of rare and common human diseases. Here we report a method for whole-exome sequencing coupling Roche/NimbleGen whole exome arrays to the Illumina DNA sequencing platform. We demonstrate the ability to capture approximately 95% of the targeted coding sequences with high sensitivity and specificity for detection of homozygous and heterozygous variants. We illustrate the utility of this approach by making an unanticipated genetic diagnosis of congenital chloride diarrhea in a patient referred with a suspected diagnosis of Bartter syndrome, a renal salt-wasting disease. The molecular diagnosis was based on the finding of a homozygous missense D652N mutation at a position in SLC26A3 (the known congenital chloride diarrhea locus) that is virtually completely conserved in orthologues and paralogues from invertebrates to humans, and clinical follow-up confirmed the diagnosis. To our knowledge, whole-exome (or genome) sequencing has not previously been used to make a genetic diagnosis. Five additional patients suspected to have Bartter syndrome but who did not have mutations in known genes for this disease had homozygous deleterious mutations in SLC26A3. These results demonstrate the clinical utility of whole-exome sequencing and have implications for disease gene discovery and clinical diagnosis.

Choi, Murim; Scholl, Ute I.; Ji, Weizhen; Liu, Tiewen; Tikhonova, Irina R.; Zumbo, Paul; Nayir, Ahmet; Bakkaloglu, Aysin; Ozen, Seza; Sanjad, Sami; Nelson-Williams, Carol; Farhi, Anita; Mane, Shrikant; Lifton, Richard P.

2009-01-01

338

The analysis of one or two blastomeres for PGD using fluorescence in-situ hybridization  

Microsoft Academic Search

BACKGROUND: The analysis of one or two blastomeres for PGD using fluorescence in-situ hybridization (FISH) is debated. The proportion of analysable embryos, false negatives, false positives, sensitivity, specificity, negative pre- dictive value (NPV), positive predictive value (PPV) and efficiency were evaluated when one or two blastomeres were analysed. METHODS: Embryos of patients having PGD for aneuploidy screening were assigned non-randomly

An Michiels; Elvire Van Assche; Inge Liebaers; André Van Steirteghem; Catherine Staessen

339

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

2013-01-02

340

An improved fixation technique for fluorescence in situ hybridization for preimplantation genetic diagnosis  

Microsoft Academic Search

Objective: To improve existing preimplantation genetic diagnosis fixation techniques.Design: Prospective randomized in vitro study.Setting: Academic medical center.Patient(s): None.Intervention(s): None.Main Outcome Measure(s): The intensity and clarity of fluorescence in situ hybridization (FISH) signals and the percentage of successfully fixed blastomeres.Result(s): The described fixation technique resulted in 100% fixation and 100% adequate FISH signals. Two conventional techniques resulted in 94% and 87%

Dmitri I Dozortsev; Kevin T McGinnis

2001-01-01

341

Preimplantation genetic diagnosis of chromosome balance in embryos from a patient with a balanced reciprocal translocation  

Microsoft Academic Search

USA Duplications or deletions are present in a high percentage of the gametes produced by individuals carrying balanced translocations. Preimplantation genetic diagnosis was used to examine chromosome balance in embryos from a patient having a reciprocal translocation within the short arms of chromosomes 5 and 8 (46,XX,t(5;8)(p13;p23)). This woman has two sisters with the translocation unbalanced, resulting in a partial

Kenneth E. Pierce; Lisa M. Fitzgerald; Machelle M. Seibel; Moshe Zilberstein

1998-01-01

342

Case report: birth of healthy twins after preimplantation genetic diagnosis of propionic acidemia  

Microsoft Academic Search

Purpose  Development of an ad hoc protocol for the preimplantion genetic diagnosis of propionic acidemia in a couple carrying the mutations c.737G>T (G246V)\\u000a and c.1218del14ins12 (ins\\/del) in the PCCB gene. Propionic acidemia is an autosomal recessive metabolic disorder where the body is unable to process certain parts of\\u000a proteins and lipids. Symptoms manifest few days after birth and sometimes progress to

Trinitat M. Alberola; Rosa Bautista-Llácer; Xavier Vendrell; Elena García-Mengual; Merche Pardo; Maria Vila; Carmen Calatayud

2011-01-01

343

High resolution melting: improvements in the genetic diagnosis of hypertrophic cardiomyopathy in a Portuguese cohort  

PubMed Central

Background Hypertrophic Cardiomyopathy (HCM) is a complex myocardial disorder with a recognized genetic heterogeneity. The elevated number of genes and mutations involved in HCM limits a gene-based diagnosis that should be considered of most importance for basic research and clinical medicine. Methodology In this report, we evaluated High Resolution Melting (HRM) robustness, regarding HCM genetic testing, by means of analyzing 28 HCM-associated genes, including the most frequent 4 HCM-associated sarcomere genes, as well as 24 genes with lower reported HCM-phenotype association. We analyzed 80 Portuguese individuals with clinical phenotype of HCM allowing simultaneously a better characterization of this disease in the Portuguese population. Results HRM technology allowed us to identify 60 mutated alleles in 72 HCM patients: 49 missense mutations, 3 nonsense mutations, one 1-bp deletion, one 5-bp deletion, one in frame 3-bp deletion, one insertion/deletion, 3 splice mutations, one 5'UTR mutation in MYH7, MYBPC3, TNNT2, TNNI3, CSRP3, MYH6 and MYL2 genes. Significantly 22 are novel gene mutations. Conclusions HRM was proven to be a technique with high sensitivity and a low false positive ratio allowing a rapid, innovative and low cost genotyping of HCM. In a short return, HRM as a gene scanning technique could be a cost-effective gene-based diagnosis for an accurate HCM genetic diagnosis and hopefully providing new insights into genotype/phenotype correlations.

2012-01-01

344

[Study on medical diagnosis decision support system for heart diseases based on hybrid genetic algorithm].  

PubMed

In this study, a medical diagnosis decision support system based on hybrid genetic algorithm has been established to support the diagnosis of five common heart diseases (coronary heart disease, rheumatic valvular heart disease, hypertensive heart disease, chronic cor pulmonale and congenital heart disease). A heart disease database consisting of 352 samples was used for constructing and testing the performance of system. Cross-validation of the experimental results indicate that the system we established shows high capability of classifying these five kinds of heart diseases, the mean accuracy of classification is as high as 90.6%, and the user accuracy and procedure accuracy of each disease are both above 85.0%, showing great application prospect of supporting heart diseases diagnosis in clinics. PMID:15143564

Yan, Hongmei; Ding, Xiaojun; Peng, Chenglin; Xiao, Shouzhong

2004-04-01

345

PGD analysis for aneuploidy in a patient heterozygous for a polymorphism of chromosome 16(16qh?)  

Microsoft Academic Search

Methods A polymorphism of chromosome 16 (16qh?) was detected in PGD analysis for aneuploidy using a probe for the centromeric region of chromosome 16. The lack of pericentromeric heterochromatin in one of the chromosomes 16 could lead to misdiagnosis in PGD. PGD analysis using telomeric probes for this chromosome was performed to confirm the polymorphism as well as to avoid

Pere Colls; Mireia Sandalinas; Kelly Pagidas; Santiago Munné

2004-01-01

346

Variations in the expression of the gene Pgd due to the effect of chromosomal rearrangements in Drosophila melanogaster  

Microsoft Academic Search

The effects of chromosomal rearrangements on the expression of the gene Pgd coding for 6-phosphogluconate dehydrogenase (PGD) was studied in D. melanogaster. Of 21 chromosomal rearrangements examined, 2 produced complete loss of PGD activity, 10 markedly decreased it, 3 slightly increased it, and 6 had no appreciable effect. The effect of some rearrangements can be restricted to the larval stage.

Sergei Y. Slobodyanyuk; Oleg L. Serov

1983-01-01

347

Selective modulation of chemokinesis, degranulation, and apoptosis in eosinophils through the PGD 2 receptors CRTH2 and DP  

Microsoft Academic Search

Background: PGD2 is the major prostanoid released by mast cells during an allergic response. Its role in the allergic response, however, remains unclear. Objective: Because the accumulation of eosinophils is a feature of allergic reactions, we investigated the role of PGD2 in the modulation of eosinophil function. Methods: Circulating human eosinophils were isolated and challenged with PGD2. The effects of

Francois G. Gervais; Rani P. G. Cruz; Anne Chateauneuf; Stephen Gale; Nicole Sawyer; Francois Nantel; Kathleen M. Metters; Gary P. O'Neill

2001-01-01

348

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

PubMed

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

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

2013-08-31

349

Genetic diagnosis by whole exome capture and massively parallel DNA sequencing.  

PubMed

Protein coding genes constitute only approximately 1% of the human genome but harbor 85% of the mutations with large effects on disease-related traits. Therefore, efficient strategies for selectively sequencing complete coding regions (i.e., "whole exome") have the potential to contribute to the understanding of rare and common human diseases. Here we report a method for whole-exome sequencing coupling Roche/NimbleGen whole exome arrays to the Illumina DNA sequencing platform. We demonstrate the ability to capture approximately 95% of the targeted coding sequences with high sensitivity and specificity for detection of homozygous and heterozygous variants. We illustrate the utility of this approach by making an unanticipated genetic diagnosis of congenital chloride diarrhea in a patient referred with a suspected diagnosis of Bartter syndrome, a renal salt-wasting disease. The molecular diagnosis was based on the finding of a homozygous missense D652N mutation at a position in SLC26A3 (the known congenital chloride diarrhea locus) that is virtually completely conserved in orthologues and paralogues from invertebrates to humans, and clinical follow-up confirmed the diagnosis. To our knowledge, whole-exome (or genome) sequencing has not previously been used to make a genetic diagnosis. Five additional patients suspected to have Bartter syndrome but who did not have mutations in known genes for this disease had homozygous deleterious mutations in SLC26A3. These results demonstrate the clinical utility of whole-exome sequencing and have implications for disease gene discovery and clinical diagnosis. PMID:19861545

Choi, Murim; Scholl, Ute I; Ji, Weizhen; Liu, Tiewen; Tikhonova, Irina R; Zumbo, Paul; Nayir, Ahmet; Bakkalo?lu, Ay?in; Ozen, Seza; Sanjad, Sami; Nelson-Williams, Carol; Farhi, Anita; Mane, Shrikant; Lifton, Richard P

2009-10-27

350

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.

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

2013-01-01

351

Synthesis and evaluation of 2,3-dinorprostaglandins: Dinor-PGD1 and 13-epi-dinor-PGD1 are peroxisome proliferator-activated receptor ?/? dual agonists.  

PubMed

2,3-Dinorprostaglandins (dinor-PGs) have been regarded as ?-oxidation products of arachidonic-acid-derived prostaglandins, but their biological activities in mammalian cells remain unclear. On the other hand, C18 polyunsaturated fatty acids (PUFAs), such as ?-linolenic acid (GLA), have various biological activities, and dinor-PGs are speculated to be biosynthesized from GLA. Here, we synthesized dinor-PGs that may possibly be derived from GLA and examined their activities towards peroxisome proliferator-activated receptors (PPARs). Dinor-PGD1 (1) and its epimer 13-epi-dinor-PGD1 (epi-1) were found to be dual agonists for PPAR?/?, whereas PGD2 derived from arachidonic acid is selective for PPAR?. Thus, GLA-derived dinor-PGs may have unique biological roles. PMID:23566516

Sato, Ayato; Dodo, Kosuke; Makishima, Makoto; Hashimoto, Yuichi; Sodeoka, Mikiko

2013-03-21

352

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

PubMed

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

Lacombe, Didier; Toussaint, Eva

2007-03-01

353

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

NASA Astrophysics Data System (ADS)

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

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

1996-04-01

354

PGD to reduce reproductive risk: the case of mitochondrial DNA disorders  

Microsoft Academic Search

This paper discusses the pros and cons of introducing PGD for mitochondrial DNA (mtDNA) disorders such as NARP (Neurogenic muscle weakness, Ataxia, Retinis Pigmentosa)\\/Leigh, MELAS (Mitochondrial myopathy, Encephalo- pathy, Lactic acidosis, and Stroke-like episodes), private mtDNA mutations and LHON (Leber Hereditary Optic Neuropathy). Although there is little experience with PGD for mtDNA disorders, it is reasonable to assume that in

A. L. Bredenoord; W. Dondorp; G. Pennings; C. E. M. De Die-Smulders; G. De Wert

2008-01-01

355

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

Microsoft Academic Search

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

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

2009-01-01

356

Prostaglandin D 2 (PGD 2 ) — A potent coronary vasoconstrictor agent in the guinea pig isolated heart  

Microsoft Academic Search

The action of prostaglandin D2 (PGD2) on myocardial force of contraction (MFC) and coronary vascular resistance (CVR) was studied in the isovolumetrically perfused guinea pig heart at constant driving frequency (180 beats\\/min). PGD2 (2·10-9–1·10-6 M) produced a concentration-dependent increase in the CVR while the MFC remained unchanged. The ED50 (50% of maximum response) of the coronary vasomotor action amounted to

K. Schrör

1978-01-01

357

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

NASA Astrophysics Data System (ADS)

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

Zhang, Yongxiang; Randall, R. B.

2009-07-01

358

Diagnosis and Genetic Counseling for Friedreich's Ataxia: A time for consideration of TP-PCR in an Indian Setup  

PubMed Central

Background and Introduction: Expansion of GAA triplet repeats in the first intron of the frataxin gene causes Friedreich’s ataxia. Genetic testing in such condition is important to initiate the appropriate genetic counseling for the family members. The conventional genetic tests used in the diagnosis of Friedreich’s ataxia are southern blot, short and long PCR. Recently, triplet repeat primed polymerase chain reaction (TP-PCR) methodology was described in the diagnosis of Friedreich’s ataxia, especially for detection of long repeats. Accurate genetic diagnosis of Friedreich’s ataxia helps in differentiating it from other ataxias and helps provide appropriate genetic counseling for such families. Extended family screening and genetic counseling can prevent birth of children with Friedreich’s ataxia in these families. Materials and Methods: TP-PCR was carried out in 37 samples obtained from Neurology clinic, Sanjay Gandhi Post Graduate Institute of Medical Sciences. The amplified products were subjected to genotyping on a ABI 310 genetic analyser. For heterozygosity, the samples were processed for short and long range PCR. Results: A total of 37 samples of suspected cases of Friedreich ataxia were analysed. Of these, 81% samples were confirmed as Friedreich ataxia and 19% of samples were found to be negative for Friedreich’s ataxia by TP-PCR. Extended family screening was done in 2 of the families. Among the 7 individuals screened, 4 were identified as carriers and genetic counseling was provided to them. Conclusions: This is first report from India which describes the molecular diagnosis of Friedreich’s ataxia by TP-PCR, its utility in extended family screening and genetic counseling. It qualifies as a highly reliable, sensitive and robust technique that can easily be set up in any laboratory.

Muthuswamy, S; Agarwal, S; Dalal, AR

2013-01-01

359

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

PubMed

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

Le Ber, I

2013-09-04

360

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

PubMed Central

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

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

2012-01-01

361

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

PubMed Central

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

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

2012-01-01

362

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

2013-03-12

363

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.

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

2011-01-01

364

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

2013-04-16

365

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

PubMed Central

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

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

2012-01-01

366

Induction of apoptosis in non-small cell lung carcinoma A549 cells by PGD? metabolite, 15d-PGJ?.  

PubMed

PGD2 (prostaglandin D2) is a mediator in various pathophysiological processes, including inflammation and tumorigenesis. PGD2 can be converted into active metabolites and is known to activate two distinct receptors, DP (PGD2 receptor) and CRTH2/DP2 (chemoattractant receptor-homologous molecule expressed on Th2 cells). In the past, PGD2 was thought to be involved principally in the process of inflammation. However, in recent years, several studies have shown that PGD2 has anti-proliferative ability against tumorigenesis and can induce cellular apoptosis via activation of the caspase-dependent pathway in human colorectal cancer cells, leukaemia cells and eosinophils. In the lung, where PGD2 is highly released when sensitized mast cells are challenged with allergen, the mechanism of PGD2-induced apoptosis is unclear. In the present study, A549 cells, a type of NSCLC (non-small cell lung carcinoma), were treated with PGD2 under various conditions, including while blocking DP and CRTH2/DP2 with the selective antagonists BWA868C and ramatroban respectively. We report here that PGD2 induces A549 cell death through the intrinsic apoptotic pathway, although the process does not appear to involve either DP or CRTH2/DP2. Similar results were also found with H2199 cells, another type of NSCLC. We found that PGD2 metabolites induce apoptosis effectively and that 15d-PGJ2 (15-deoxy-?12,14-prostaglandin J2) is a likely candidate for the principal apoptotic inducer in PGD2-induced apoptosis in NSCLC A549 cells. PMID:21999315

Wang, Jun-Jie; Mak, Oi-Tong

2011-11-01

367

Successful Use of a Laser for Human Embryo Biopsy in Preimplantation Genetic Diagnosis: Report of Two Cases  

Microsoft Academic Search

Purpose:The use of Tyrode's acid to drill the zona pellucida for embryo biopsy is the most widely used methodology in preimplantation genetic diagnosis. Instead of this, we propose the use of a 1.48-µm diode noncontact laser, which is quicker, simpler, and safer.

M. Boada; M. Carrera; C. De La Iglesia; M. Sandalinas; P. N. Barri; A. Veiga

1998-01-01

368

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

Microsoft Academic Search

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

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

2007-01-01

369

Counselling following diagnosis of a fetal abnormality: the differing approaches of obstetricians, clinical geneticists, and genetic nurses  

Microsoft Academic Search

Women receiving a positive diagnosis of an abnormality during pregnancy may be counselled about a termination by one of several types of health professionals including obstetricians, geneticists, and genetic nurses. There is anecdotal evidence to suggest that these groups differ in both their approaches to counselling and their attitudes towards abnormality. The aim of the current study is to document

T Marteau; H Drake; M Bobrow

1994-01-01

370

Linkage relationships between ALPL, ENO1, GPI, PGD, and TGFB1 on porcine chromosome 6.  

PubMed

A five-point linkage map has been established between the loci encoding liver/bone/kidney alkaline phosphatase (ALPL), enolase 1-alpha (ENO1), glucose-phosphate isomerase (GPI), phosphogluconate dehydrogenase (PGD), and transforming growth factor beta 1 (TGFB1) in swine. Linkage analysis was performed using the Meishan x Yorkshire three-generation reference pedigree at the University of Illinois (n = 91). Previously ENO1, GPI, PGD, and TGFB1 were mapped to porcine chromosome 6q by in situ hybridization but the linkage relations of TGFB1 and ENO1 with other loci in this group were not investigated. Based on mapping data from human chromosomes 1 and 19 and mouse chromosomes 4 and 7, it was postulated that ALPL should reside among or near these loci. Restriction fragment length polymorphisms were identified for ALPL, ENO1, and TGFB1. GPI (EC 5.3.1.9) and PGD (EC 1.1.1.44) phenotypes were determined by agarose gel electrophoresis of isozymes. Marker data were analyzed using the MLINK (two locus) and ILINK (multilocus) programs from LINKAGE (version 5.10). The most likely locus order between GPI-TGFB1-(PGD-ENO1)-ALPL with recombination rates of 0.049, 0.044, 0.000, and 0.156, respectively, could not be significantly determined. The maximum five-point lod score was the same to four decimal places irrespective of the order of ENO1 and PGD. This indicates that ENO1 and PGD are very closely linked and that ALPL is located telomeric to the established linkage group on pig chromosome 6. PMID:8104872

Clamp, P A; Feltes, R; Shalhevet, D; Beever, J E; Atac, E; Schook, L B

1993-08-01

371

Proper general decomposition (PGD) for the resolution of Navier-Stokes equations  

NASA Astrophysics Data System (ADS)

In this work, the PGD method will be considered for solving some problems of fluid mechanics by looking for the solution as a sum of tensor product functions. In the first stage, the equations of Stokes and Burgers will be solved. Then, we will solve the Navier-Stokes problem in the case of the lid-driven cavity for different Reynolds numbers (Re = 100, 1000 and 10,000). Finally, the PGD method will be compared to the standard resolution technique, both in terms of CPU time and accuracy.

Dumon, A.; Allery, C.; Ammar, A.

2011-02-01

372

6'-Hydroxyoxosorbicillinol, a new lipoxygenase inhibitor and PGD2/LTB4 release suppressor from Penicillium sp.  

PubMed

A new lipoxygenase inhibitor, 6'-hydroxyoxosorbicillinol (1, C(14) H(16)O(6)), was identified from a culture of Penicillium sp. A known compound, oxosorbicillinol (2, C(14)H(16)O(5)), was also isolated. Compound 1 showed an approximately 10 times greater inhibitory effect on soybean lipoxygenase (IC(50), 16 µM) than 2 (IC(50), 150 µM), and also showed prostaglandin D(2) (PGD(2)) and leucotriene B(4) (LTB(4)) release suppression activity (IC(50), 10 µM for PGD(2) and 100 µM for LTB(4)). PMID:22785490

Komoda, Toshikazu; Nishikawa, Masazumi

2012-07-07

373

Anti-inflammatory role of PGD2 in acute lung inflammation and therapeutic application of its signal enhancement  

PubMed Central

We investigated the role of prostaglandin D2 (PGD2) signaling in acute lung injury (ALI), focusing on its producer–effector interaction in vivo. Administration of endotoxin increased edema and neutrophil infiltration in the WT mouse lung. Gene disruption of hematopoietic PGD synthase (H-PGDS) aggravated all of the symptoms. Experiments involving bone marrow transplantation between WT and H-PGDS–deficient mice showed that PGD2 derived from alveolar nonhematopoietic lineage cells (i.e., endothelial cells and epithelial cells) promotes vascular barrier function during the early phase (day 1), whereas neutrophil-derived PGD2 attenuates its own infiltration and cytokine expression during the later phase (day 3) of ALI. Treatment with either an agonist to the PGD2 receptor, DP, or a degradation product of PGD2, 15-deoxy-?12,14-PGJ2, exerted a therapeutic action against ALI. Data obtained from bone marrow transplantation between WT and DP-deficient mice suggest that the DP signal in alveolar endothelial cells is crucial for the anti-inflammatory reactions of PGD2. In vitro, DP agonism directly enhanced endothelial barrier formation, and 15-deoxy-?12,14-PGJ2 attenuated both neutrophil migration and cytokine expression. These observations indicate that the PGD2 signaling between alveolar endothelial/epithelial cells and infiltrating neutrophils provides anti-inflammatory effects in ALI, and suggest the therapeutic potential of these signaling enhancements.

Murata, Takahisa; Aritake, Kosuke; Tsubosaka, Yoshiki; Maruyama, Toshihiko; Nakagawa, Takayuki; Hori, Masatoshi; Hirai, Hiroyuki; Nakamura, Masataka; Narumiya, Shuh; Urade, Yoshihiro; Ozaki, Hiroshi

2013-01-01

374

Anti-inflammatory role of PGD2 in acute lung inflammation and therapeutic application of its signal enhancement.  

PubMed

We investigated the role of prostaglandin D2 (PGD2) signaling in acute lung injury (ALI), focusing on its producer-effector interaction in vivo. Administration of endotoxin increased edema and neutrophil infiltration in the WT mouse lung. Gene disruption of hematopoietic PGD synthase (H-PGDS) aggravated all of the symptoms. Experiments involving bone marrow transplantation between WT and H-PGDS-deficient mice showed that PGD2 derived from alveolar nonhematopoietic lineage cells (i.e., endothelial cells and epithelial cells) promotes vascular barrier function during the early phase (day 1), whereas neutrophil-derived PGD2 attenuates its own infiltration and cytokine expression during the later phase (day 3) of ALI. Treatment with either an agonist to the PGD2 receptor, DP, or a degradation product of PGD2, 15-deoxy-?(12,14)-PGJ2, exerted a therapeutic action against ALI. Data obtained from bone marrow transplantation between WT and DP-deficient mice suggest that the DP signal in alveolar endothelial cells is crucial for the anti-inflammatory reactions of PGD2. In vitro, DP agonism directly enhanced endothelial barrier formation, and 15-deoxy-?(12,14)-PGJ2 attenuated both neutrophil migration and cytokine expression. These observations indicate that the PGD2 signaling between alveolar endothelial/epithelial cells and infiltrating neutrophils provides anti-inflammatory effects in ALI, and suggest the therapeutic potential of these signaling enhancements. PMID:23479612

Murata, Takahisa; Aritake, Kosuke; Tsubosaka, Yoshiki; Maruyama, Toshihiko; Nakagawa, Takayuki; Hori, Masatoshi; Hirai, Hiroyuki; Nakamura, Masataka; Narumiya, Shuh; Urade, Yoshihiro; Ozaki, Hiroshi

2013-03-11

375

PCR from single cells for preimplantation diagnosis.  

PubMed

The detection of genetic defects in human embryos following in vitro fertilization (IVF) or preimplantation genetic diagnosis (PGD) allows the selection and transfer of unaffected embryos in couples known to be at risk of transmitting an inherited disorder. This avoids the need to termiate an affected pregnancy, following prenatal diagnosis at later stages (1). Diagnosis of a single gene defect is usually performed on one or two single cells (blastomeres) biopsied from 8- to 10-cell embryos on the 3rd d postinsemination using nested polymerase chain reaction (PCR) to amplify informative fragments. Nested PCR allows amplification from a limited number of target sequences (2), and under carefully optimized conditions, amplification of as few as one or two target copies present in a single haploid or diploid cell is possible (3-5). PGD was first achieved for X-linked diseases by determining the sex of the embryos using a Y chromosome-specific repetitive sequence and selective transfer of only female embryos (6). More recently, specific diagnosis has been achieved for cystic fibrosis (CF), by amplifying across the cystic fibrosis transmembrane regulator (CFTR) gene †F508 locus (7) and for Lesch-Nyhan syndrome by amplifying across a familial base substitution nullifying a natural XhoI restriction site in the hypoxanthine phophoribosyl transferase (HPRT) gene (8). In both instances, nested PCR strategies were chosen to amplify the mutated sequence allowing sufficient amplification for detection on ethidium bromide-stained gels. The limited cycling with the outer primers (20 cycles) reduces nonspecific amplification, and only specific fragments that contain the complementary sequence to the internal primers are amplified to a detectable level in the second round of PCR. Although extra handling is involved, any genomic contaminant introduced after the first round of amplification would not be amplified to a detectable level by the inner primers alone. The efficiency of the second amplification is improved because the denaturation of the first amplification product (amplicon) is easier. Also, the great excess of these amplicons compared with nonspecific sequences eliminates competition, thereby enhancing specificity and yield. PMID:21374522

Ray, P F; Handyside, A H

1996-01-01

376

Cytotoxicity of combinations of prostaglandin D2 (PGD2) and antitumor drugs for B16 melanoma cells in culture.  

PubMed

Prostaglandin D2 (PGD2) is lethal to murine and human melanoma cells at high doses, but synchronizes cells at G1 at non-toxic doses (2.5 or 5 micrograms/ml). We tested the lethality to B16 mouse melanoma cells of combinations of PGD2 with anticancer drugs. The drugs selected were mostly those used in treating human melanoma: actinomycin D, Bleomycin, BCNU, cis-platin, melphalan, 5-fluorouracil, and 1-beta-D-arabinofuranosylcytosine (ara-C). PGD2 was combined with the drugs according to 3 different protocols: An asynchronous culture was given a long term (24 hr) exposure simultaneously to PGD2 + drug. Combinations with Bleomycin, ara-C or melphalan were additive or slightly antagonistic whereas PGD2 plus actinomycin D was significantly antagonistic. Cells synchronized in G1 by 24 hr PGD2 exposure were then given a short-term (2 hr) treatment with PGD2 + drug. Combinations with cis-platin, Bleomycin, BCNU or 5-fluorouracil were additive or slightly antagonistic, whereas melphalan and actinomycin D combinations were significantly antagonistic. Cells were released from a PGD2-induced G1 block and were exposed to drug at different times during cell progression. Actinomycin D was antagonistic when added immediately after release from the G1 block, but was significantly synergistic when added 10 to 12 hr later. The effect of the combinations cannot be explained by available cell cycle or biochemical information. The antagonism between PGD2 and several of the drugs resembles the "cytoprotective" effect of PGD2 towards various noxious agents. PMID:3473056

Bhuyan, B K; Badiner, G J; Adams, E G; Chase, R

1986-01-01

377

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

378

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

PubMed Central

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

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

2011-01-01

379

The in vivo and in vitro efficiency and efficacy of PGD for aneuploidy  

Microsoft Academic Search

Preimplantation genetic diagnosis for aneuploidy was implemented on 1782 morphologically normal embryos generated in vitro by patients with a poor prognosis of pregnancy. Only 592 of them (34%) were diagnosed as chromosomally normal. Embryo transfer was accomplished in 240 cycles resulting in 79 clinical pregnancies (33%) and an implantation rate of 22.6%. The in vitro efficiency of the procedure was

Luca Gianaroli; M. C Magli; A. P Ferraretti

2001-01-01

380

Synchronous activation of both parental alleles at the 6-PGD locus of Japanese quail embryos  

Microsoft Academic Search

The gene locus for the enzyme 6-phosphogluconate dehydrogenase belongs to that part of the genome which is activated at the beginning of embryonic development. The present experiment, utilizing three alleles at this autosomally inherited locus of the Japanese quail, was designed to show whether exhaustion of maternally stored 6-PGD is followed by maternally hemizygous de novo synthesis of the same

S. Ohno; C. Stenius; L. C. Christian; C. Harris

1968-01-01

381

Gene modulation in Drosophila : Dosage compensation of Pgd + and Zw + genes  

Microsoft Academic Search

The sex-linked Pgd+ and Zw+ genes of Drosophila melanogaster and their associated enzyme activities 6-phosphogluconate dehydrogenase and glucose 6-phosphate dehydrogenase were employed in an analysis of the relationship between dosage compensation and the location of genes in the genome. In the genotypes examined, the enzyme activity specified by each copy of the gene is twice in males what it is

James T. Bowman; John R. Simmons

1973-01-01

382

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

Microsoft Academic Search

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

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

2008-01-01

383

Diagnosis of Familial Hypercholesterolemia in General Practice Using Clinical Diagnostic Criteria or Genetic Testing as Part of Cascade Genetic Screening  

Microsoft Academic Search

Background: Too few familial hypercholesterolemia (FH) patients are diagnosed. The most cost-effective strategy to diagnose FH is to examine first-degree relatives of already diagnosed patients. This is referred to as cascade genetic screening. Methods and Results: One thousand eight hundred and five first-degree relatives of index patients with molecularly defined FH consented to cascade genetic screening by the use of

Trond P. Leren; Tora Himle Finborud; Turid E. Manshaus; Leiv Ose; Knut Erik Berge

2008-01-01

384

The critical and expanding role of genetics in assisted reproduction.  

PubMed

With the progress of the human gene mapping initiative, it is expected that the entire genome will be mapped within two years. A significant use for these data will centre on testing for genetic disease. Professionals associated with assisted reproduction are presented with a very special subset of the population, namely, couples suffering from infertility. Infertility may occur in the male, the female or both partners and may be heritable. Infertility, subfertility or recurrent spontaneous miscarriage is associated with chromosomal or genetic anomalies, suggesting that basic developmental genetics should be a part of the education of the physician or clinical embryologist. A review of the most common infertility-associated chromosomal and genetic diseases for which genetic testing has become routine in infertile parents and in the products of assisted reproduction through preimplantation genetic diagnosis (PGD) and prenatal testing follows. Less common genetic diseases that have compromising effects on reproduction and which are likely to be encountered by providers of assisted reproduction are also considered. PMID:10913952

Kent-First, M

2000-07-01

385

Vitamin D status at breast cancer diagnosis: correlation with tumor characteristics, disease outcome, and genetic determinants of vitamin D insufficiency.  

PubMed

We correlated serum 25-hydroxyvitamin D(3) (25OHD) levels with tumor characteristics and clinical disease outcome in breast cancer patients and assessed the impact of genetic determinants of vitamin D insufficiency. We collected serum from 1800 early breast cancer patients at diagnosis, measured 25OHD by radioimmunoassay (RIA), and determined genetic variants in vitamin D-related genes by Sequenom. Multivariable regression models were used to correlate 25OHD levels with tumor characteristics. Cox proportional hazard models were used to assess overall survival (OS), disease-specific survival (DSS), and disease-free interval (DFI). Lower 25OHD serum levels significantly correlated with larger tumor size at diagnosis (P = 0.0063) but not with lymph node invasion, receptor status, or tumor grade. Genetic variants in 25-hydroxylase (CYP2R1) and vitamin D-binding (DBP) protein significantly determined serum 25OHD levels but did not affect the observed association between serum 25OHD and tumor size. High serum 25OHD (>30 ng/mL) at diagnosis significantly correlated with improved OS (P = 0.0101) and DSS (P = 0.0192) and additionally had a modest effect on DFI, which only became apparent after at least 3 years of follow-up. When considering menopausal status, serum 25OHD had a strong impact on breast cancer-specific outcome in postmenopausal patients [hazards ratios for 25OHD >30 ng/mL versus ?30 ng/mL were 0.15 (P = 0.0097) and 0.43 (P = 0.0172) for DSS and DFI, respectively], whereas no association could be demonstrated in premenopausal patients. In conclusion, high vitamin D levels at early breast cancer diagnosis correlate with lower tumor size and better OS, and improve breast cancer-specific outcome, especially in postmenopausal patients. PMID:22623648

Hatse, Sigrid; Lambrechts, Diether; Verstuyf, Annemieke; Smeets, Ann; Brouwers, Barbara; Vandorpe, Thijs; Brouckaert, Olivier; Peuteman, Gilian; Laenen, Annouschka; Verlinden, Lieve; Kriebitzsch, Carsten; Dieudonné, Anne-Sophie; Paridaens, Robert; Neven, Patrick; Christiaens, Marie-Rose; Bouillon, Roger; Wildiers, Hans

2012-05-23

386

Response to growth hormone treatment in Prader-Willi syndrome: Auxological criteria versus genetic diagnosis.  

PubMed

AIM: The Australian Prader-Willi Syndrome (PWS) database was established to monitor the efficacy and safety of growth hormone (GH) treatment in PWS. This study aims to compare response to GH based on eligibility criteria. METHODS: Comparative study: 72 children received GH on the basis of short stature or evidence of GH deficiency (pre-2009: PWS-SS) and 94 on a genetic diagnosis (post-2009: PWS-Dx). We report on mandatory patient data for GH prescription: median and standard deviation score (SDS) for height and body mass index (BMI), waist/height ratio, bone age/chronological age ratio and adverse events. Comparisons were made using non-parametric tests. RESULTS: At baseline, the PWS-SS cohort was shorter (height SDS: -2.6 vs. -1.1, P?

Scheermeyer, Elly; Hughes, Ian; Harris, Mark; Ambler, Geoff; Crock, Patricia; Verge, Charles F; Craig, Maria E; Bergman, Phil; Werther, George; van Driel, Mieke; Davies, Peter Sw; Choong, Catherine Sy

2013-06-19

387

Prediction of the halothane (Hal) genotypes by means of linked marker loci (Phi, Po2, Pgd) in Quebec Landrace pigs.  

PubMed Central

Quebec Landrace pigs (n = 896) were halothane tested and blood samples were taken for the determination of Phi, Po2 and Pgd phenotypes. The incidence of the halothane positive pigs was 5.3%. The frequencies of the favorable alleles PhiA, Po2S and PdgA were respectively 29.2%, 39.6% and 64.4%. The highest linkage disequilibrium was found between Hal-Phi (0.0606) followed by Hal-Pgd (0.0428) and Hal-Po2 (-0.0308). Alleles PhiB, PgdB and Po2F were associated respectively with 97%, 81% and 74% of Haln haplotypes. It was concluded that a selection in order to increase the favorable marker loci PhiA and PgdA would reduce the Haln frequency in Quebec Landrace pigs.

Doize, F; Roux, I; Martineau-Doize, B; DeRoth, L

1990-01-01

388

Assisted procreation and its relationship to genetics and eugenics.  

PubMed

The article below is intended to reflect on whether or not a eugenic tendency constitutes an intrinsic element of human fertilization in vitro. The author outlines ideas and circumstances which characterized the foundation and propagation of eugenics between the eighteenth and nineteenth centuries. A brief discussion follows on some of the standard procedures of in vitro fertilization, and in particular, those which manifest a trace or hint of eugenics--heterologous fertilization and sperm banking, preimplantation genetic diagnosis (PGD) and embryo selection--practices which, nonetheless, are used on a large scale and shed light on both the essence of procreative medicine and on the current cultural environment. The objective of the article is to explore whether it is possible to eliminate the eugenic connotations without foregoing the benefits of technical and scientific progress. PMID:19580100

Ricci, Mariella Lombardi

2009-01-01

389

Proper general decomposition (PGD) for the resolution of Navier–Stokes equations  

Microsoft Academic Search

In this work, the PGD method will be considered for solving some problems of fluid mechanics by looking for the solution as a sum of tensor product functions. In the first stage, the equations of Stokes and Burgers will be solved. Then, we will solve the Navier–Stokes problem in the case of the lid-driven cavity for different Reynolds numbers (Re=100,

A. Dumon; C. Allery; A. Ammar

2011-01-01

390

A model reduction technique based on the PGD for elastic-viscoplastic computational analysis  

NASA Astrophysics Data System (ADS)

In this paper a model reduction approach for elastic-viscoplastic evolution problems is considered. Enhancement of the PGD reduced model by a new iterative technique involving only elastic problems is investigated and allows to reduce CPU cost. The accuracy of the solution and convergence properties are tested on an academic example and a calculation time comparison with the commercial finite element code Abaqus is presented in the case of an industrial structure.

Relun, N.; Néron, D.; Boucard, P. A.

2013-01-01

391

Community-Based Program for the Diagnosis and Prevention of Genetic Disorders in Cuba  

Microsoft Academic Search

The author’s experience of 20 years as director of the medical genetic services program in Cuba is presented. The setting of the infrastructure for equipment and the training of personnel for the medical genetic program began in 1981 in the city of Havana, and was progressively extended to cover the whole country in 1988. Between 1982 and 2002, 2.8 million

Luis Heredero-Baute

2004-01-01

392

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

NASA Astrophysics Data System (ADS)

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

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

2012-02-01

393

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

PubMed

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

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

394

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

PubMed Central

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

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

2010-01-01

395

Analysis of five polymorphic DNA markers for indirect genetic diagnosis of haemophilia A in the Brazilian population.  

PubMed

Hemophilia A is an X-linked, inherited, bleeding disorder caused by the partial or total inactivity of the coagulation factor VIII (FVIII). Due to difficulties in the direct recognition of the disease-associated mutation in the F8 gene, indirect diagnosis using polymorphic markers located inside or close to the gene is used as an alternative for determining the segregation of the mutant gene within families and thus for detecting carrier individuals and/or assisting in prenatal diagnosis. This study characterizes the allelic and haplotype frequencies, genetic diversity, population differentiation and linkage disequilibrium of five microsatellites (F8Int1, F8Int13, F8Int22, F8Int25.3 and IKBKG) in samples of healthy individuals from São Paulo, Rio Grande do Sul and Pernambuco and of patients from São Paulo with haemophilia A to determine the degree of informativeness of these microsatellites for diagnostic purposes. The interpopulational diversity parameters highlight the differences among the analyzed population samples. Regional differences in allelic frequencies must be taken into account when conducting indirect diagnosis of haemophilia A. With the exception of IKBKG, all of the microsatellites presented high heterozygosity levels. Using the markers described, diagnosis was possible in 10 of 11 families. The F8Int22, F8Int1, F8Int13, F8Int25.3 and IKBKG microsatellites were informative in seven, six, five and two of the cases, respectively, demonstrating the effectiveness of using these microsatellites in prenatal diagnosis and in carrier identification in the Brazilian population. PMID:21649803

Massaro, J D; Wiezel, C E V; Muniz, Y C N; Rego, E M; de Oliveira, L C O; Mendes-Junior, C T; Simões, A L

2011-06-07

396

Analysis of mtDNA variant segregation during early human embryonic development: a tool for successful NARP preimplantation diagnosis  

Microsoft Academic Search

Background: Diseases arising from mitochondrial DNA (mtDNA) mutations are usually serious pleiotropic disorders with maternal inheritance. Owing to the high recurrence risk in the progeny of carrier females, “at-risk” couples often ask for prenatal diagnosis. However, reliability of such practices remains under debate. Preimplantation diagnosis (PGD), a theoretical alternative to conventional prenatal diagnosis, requires that the mutant load measured in

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

2006-01-01

397

Employing Genetic Markers to Improve Diagnosis of Thyroid Tumor Fine Needle Biopsy  

PubMed Central

Fine-Needle Aspiration (FNA) is the most widely used and cost-effective preoperative test for the initial evaluation of a thyroid nodule, although it has limited diagnostic accuracy for several types of tumors. Patients will often receive cytological report of indeterminate cytology and are referred to surgery for a more accurate diagnosis. An improved test would help physicians rapidly focus treatment on true malignancies and avoid some unnecessary treatment of benign tumors. This review will discuss current molecular markers that may improve thyroid nodule diagnosis.

Cerutti, Janete M

2011-01-01

398

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

Microsoft Academic Search

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

Yongxiang Zhang; R. B. Randall

2009-01-01

399

Implications of Genetics on the Diagnosis and Care of Patients With Parkinson Disease  

Microsoft Academic Search

he identification of several monogenic forms has established Parkinson disease (PD) as a movement disorder with a considerable genetic origin in at least a subset of patients. Four of the known forms, Parkin-, PINK1 (PTEN-induced putative kinase 1)-, DJ1-, and LRRK2 (leucine-rich repeat kinase 2)-linked PD, may present clinically as \\

Christine Klein

2006-01-01

400

Proof of principle and first cases using preimplantation genetic haplotyping – a paradigm shift for embryo diagnosis  

Microsoft Academic Search

Preimplantation genetic haplotyping (PGH) proof-of-principle was demonstrated by multiple displacement amplification (MDA) of single buccal cells from a female donor and genotyping using 12 polymorphic markers within the dystrophin gene; the known paternal genotype enabled identification of the paternal haplotype in the MDA products despite 27% allele dropout. MDA amplified DNA from 49 single human blastomeres with 100% success. The

Pamela J Renwick; Jane Trussler; Elham Ostad-Saffari; Hiva Fassihi; Cheryl Black; Peter Braude; Caroline Mackie Ogilvie; Stephen Abbs

2006-01-01

401

Is there an ethical difference between preimplantation genetic diagnosis and abortion?  

Microsoft Academic Search

When a person at risk of having a child with a genetic illness or disease wishes to have an unaffected child, this can involve difficult choices. If the pregnancy is established by sexual intercourse, the fetus can be tested early in pregnancy, and if affected a decision can be made to abort in the hope that a future pregnancy with

C Cameron; R Williamson

2003-01-01

402

What’s new in metabolic and genetic hypoglycaemias: diagnosis and management  

Microsoft Academic Search

Hypoglycaemia in children can be a life-threatening situation that needs to be assessed rigorously in order to treat efficiently\\u000a and avoid relapse that can be responsible for cerebral damage. The diagnosis of impairment in glucose homeostasis requires\\u000a the knowledge of the mechanisms regulating blood glucose concentration. The clinical history and presentation, when available,\\u000a especially the timing of hypoglycaemia with respect

Vassili Valayannopoulos; Stéphane Romano; Karine Mention; Anne Vassault; Daniel Rabier; Michel Polak; Jean-Jacques Robert; Yves de Keyzer; Pascale de Lonlay

2008-01-01

403

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

PubMed

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

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

2013-08-07

404

Ethical Dilemmas in Genetic Testing: Examples from the Cuban Program for Predictive Diagnosis of Hereditary Ataxias  

Microsoft Academic Search

Predictive testing protocols are intended to help patients affected with hereditary conditions understand their condition\\u000a and make informed reproductive choices. However, predictive protocols may expose clinicians and patients to ethical dilemmas\\u000a that interfere with genetic counseling and the decision making process. This paper describes ethical dilemmas in a series\\u000a of five cases involving predictive testing for hereditary ataxias in Cuba.

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

2011-01-01

405

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.

Keil, Margaret F.; Stratakis, Constantine A.

2009-01-01

406

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

Microsoft Academic Search

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

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

2011-01-01

407

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

PubMed

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

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

2011-01-25

408

Impact of Genetics on the Diagnosis and Treatment of Renal Cancer  

PubMed Central

Kidney cancer is a heterogeneous disease comprised of a number of histologic subtypes, each associated with unique genetic mutations, clinical features, and sensitivity to treatment. By examining families affected with the hereditary kidney cancer syndromes von Hippel-Lindau, hereditary papillary renal cell carcinoma, hereditary leiomyomatosis and renal cell carcinoma, and Birt-Hogg-Dube', researchers have been able to identify the genes responsible for these syndromes. This work has revealed that kidney cancer is fundamentally a metabolic disorder, and as such, novel targeted therapies specific to their molecular biology have been developed and employed in both the hereditary and sporadic forms of renal cell carcinoma.

Singer, Eric A.; Bratslavsky, Gennady; Middelton, Lindsay; Srinivasan, Ramaprasad; Linehan, W. Marston

2011-01-01

409

Comparison of the results of human embryo biopsy and outcome of PGD after zona drilling using acid Tyrode medium or a laser  

Microsoft Academic Search

BACKGROUND: Zona pellucida opening for blastomere removal can be done by mechanical or chemical means, or by laser. So far, only limited data on the use of laser systems for zona drilling in cases of PGD are available. METHODS: Results of embryo biopsy and outcome of PGD in two periods were compared. In the first period, acid Tyrode medium was

H. Joris; A. De Vos; R. Janssens; P. Devroey; I. Liebaers; A. Van Steirteghem

2003-01-01

410

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

PubMed

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

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

2013-06-20

411

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

2013-05-15

412

In vitro fertilization (IVF)  

MedlinePLUS

... a child may consider pre-implantation genetic diagnosis (PGD). The procedure is done about 3 -4 days ... According to the American Society for Reproductive Medicine, PGD can help parents decide which embryos to implant, ...

413

Screening and Genetic Diagnosis of Hemoglobinopathies in Southern and Northern Europe: Two Examples  

PubMed Central

Prevention of Hemoglobinopathies has developed around the world based upon the experience done in pioneering endemic countries and is now facing a new phase in non-endemic areas with a recent immigration history. We describe two situations, taking Latium (central Italy) and The Netherlands as two models for endemic and non-endemic countries both confronted with a large multi-ethnic immigrant society. We present prevention results and discuss aspects such as local knowledge and organization. We illustrate the importance of issues like information, carrier diagnostics, screening, counseling and prenatal diagnosis in particular situation of contrasting interest an different ethical opinions. We conclude by underlining the importance of implementing primary prevention at the European level, based upon better information, diagnostics and counseling.

Amato, Antonio; Giordano, Piero C.

2009-01-01

414

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.

2013-01-01

415

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

416

Genetic Grouping of Medulloblastomas by Representative Markers in Pathologic Diagnosis1  

PubMed Central

A recent analysis of the genetic features of medulloblastoma (MB) suggested classification into distinct subgroups according to gene expression profiles, including the Wingless signaling pathway-activated group (WNT group), the Sonic Hedgehog signaling pathway-activated group (SHH group), group 3, and group 4. To classify MB according to genetic features in practice, we analyzed 74 MBs using representative markers of each group. Based on immunohistochemistries (IHC), cytogenetic alterations, and a CTNNB1 mutation study, the patients were divided into the following three groups: cases showing nuclear ?-catenin and/or CTNNB1 mutation and/or monosomy 6 were included in the WNT group (14/74, 18.9%); cases expressing GAB1 were included in the SHH group (15/74, 20.2%); cases that did not show positivity for markers of the WNT or SHH group were included in the non-WNT/SHH group (45/74, 60.6%). Immunoexpression of NPR3 seemed to lack sensitivity for classifying group 3, showing diffuse positivity in only two cases. KCNA1 was not specific to group 4 because it was expressed in all groups. Cases in the WNT group showed a slightly better survival than those in the SHH or non-WNT/SHH group, although additional cases are required for statistical significance. Isochromosome 17q (P = .002) and the large cell/anaplastic variant (P = .002) were demonstrated to be poor prognostic indicators in multivariate analysis. The representative IHC and cytogenetic data facilitated the division of MBs into the WNT and SHH groups; however, more specific markers should be added for the identification of group 3 and group 4 in practice.

Min, Hye Sook; Lee, Ji Yeoun; Kim, Seung-Ki; Park, Sung-Hye

2013-01-01

417

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

SciTech Connect

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

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

1994-09-01

418

“Important to test, important to support”: attitudes toward disability rights and prenatal diagnosis among leaders of support groups for genetic disorders in Israel  

Microsoft Academic Search

To situate the North American, and to some extent, European debate regarding disability rights and prenatal diagnosis in a social and cross-cultural context, this pilot study explored the views of leaders of organizations for disability rights and support groups for people with genetic conditions in Israel, where a similar debate has not emerged. Unlike many of their counterparts in North

Aviad Raz

2004-01-01

419

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

Microsoft Academic Search

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.

O. Hiort; Q. Huang; G. H. G. Sinnecker; K. Kruse; A. Sadeghi-Nejad; H. J. Wolfe; D. W. Yandell

1993-01-01

420

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

PubMed

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

Chen, Chih-Ping

2012-03-01

421

[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

422

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

PubMed Central

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

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

1983-01-01

423

[Genetic diagnosis of phenylketonuria. III. Mutations of phenylalanine hydroxylase gene in Orientals].  

PubMed

Phenylketonuria (PKU) is an autosomal recessive disorder caused by lesions in the phenylalanine hydroxylase (PAH) gene. The recent studies on PAH mutations show the genetic drift of PKU alleles among some Oriental populations. Therefore, we searched for PKU mutations among Japanese, Chinese and Taiwanese. Direct sequencing was conducted on DNA fragments amplified by the polymerase chain reaction, using solid-phase technology involving the biotin-streptavidin system. Two new mutations (R241C and G247V) and two of the known mutant alleles (Y204C and R243Q) were found in two Taiwanese and two Chinese PKU patients, and three known mutations (R111X, Y204C and R413P) were recognized in three Japanese; two new mutations were identified in exon 7 of the PAH gene at codon 241 and codon 247, where the single base changes from C to T and from G to T substituted cysteine for arginine and valine for glycine, respectively. Further all the PAH mutations detected are common in Oriental populations as they have been thus far unreported among Caucasians. From these data as well as the clinical phenotype of the patients, we suggest that the R241C and G247V substitutions may interfere with proper enzyme function, although we have not yet performed functional studies. More detailed studies would be needed to clarify the regional distribution of mutant chromosomes in Oriental populations and other unidentified mutations. PMID:7844887

Takarada, Y; Yamashita, K; Kagawa, S; Zhang, Q Z; Matsuoka, A

1994-11-01

424

PGD and separated space variables representation for linear elasticity in 3D representation of plate domains  

NASA Astrophysics Data System (ADS)

In this paper, we focus on the simulation of linear elastic behaviour of plates using a 3D approach which numerical cost only scales like a 2D one. In the case of plates, the kinematic hypothesis introduced in plate theories to go from 3D to 2D is usually unsatisfactory where one cannot rely on St Venant's principle (usually close to the plate edges). We propose to apply the PGD (Proper Generalized Decomposition) method [1] to the simulation of the linear elastic behavior of plates. This method allows us to separately search for the in-plane and the out-of plane contributions to the 3D solution, yielding significant savings in computational cost. The method is validated on a simple case and its full potential is then presented for the simulation of the behavior of laminated composite plates.

Bognet, B.; Leygue, A.; Chinesta, F.; Poitou, A.

2011-01-01

425

Preimplantation diagnosis.  

PubMed Central

Preimplantation embryonic biopsy and analysis offer couples at increased risk of having offspring affected with a genetic disorder the possibility of an early prenatal diagnosis. For many couples, this approach would avoid the issue of the selective termination of affected fetuses. Substantial advances have been made in the area of preimplantation diagnosis, but the possible difficulties with this approach cannot be ignored. Images

Goldberg, J D; Martin, M C; Lebo, R V; Pedersen, R A

1993-01-01

426

Viability of equine embryos after puncture of the capsule and biopsy for preimplantation genetic diagnosis.  

PubMed

The equine embryo possesses a capsule that is considered essential for its survival. We assessed viability after breaching the capsule of early (Day 6) and expanded (Day 7 and 8) equine blastocysts by micromanipulation. The capsule was penetrated using a Piezo drill, and trophoblast biopsy samples were obtained for genetic analysis. Pregnancy rates for Day-6 embryos, which had intact zonae pellucidae at the time of recovery, were 3/3 for those biopsied immediately after recovery and 2/3 for those biopsied after being shipped overnight under warm (?28 °C) conditions. The pregnancy rates for encapsulated Day-7 expanded blastocysts were 5/6 for those biopsied immediately and 5/6 for those biopsied after being shipped overnight warm. Two of four encapsulated Day-8 blastocysts, 790 and 1350 ?m in diameter, established normal pregnancies after biopsy. Nine mares were allowed to maintain pregnancy, and they gave birth to nine normal foals. Biopsied cells from eight embryos that produced foals were subjected to whole-genome amplification. Sex was successfully determined from amplified DNA in 8/8 embryos. Identification of disease-causing mutations matched in the analyses of 6/6 samples for the sodium channel, voltage-gated, type IV, alpha subunit (SCN4A) gene and in 6/7 samples for the peptidylprolyl isomerase B (PPIB) gene, in embryo-foal pairs. Thus, the capsule of the equine embryo can be breached without impairing viability. Further work is needed to determine whether this breach is transient or permanent. These findings are relevant to the understanding of equine embryo development and to the establishment of methods for micromanipulation and embryo cryopreservation in this species. PMID:20843896

Choi, Y H; Gustafson-Seabury, A; Velez, I C; Hartman, D L; Bliss, S; Riera, F L; Roldán, J E; Chowdhary, B; Hinrichs, K

2010-09-15

427

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

PubMed

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

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

2013-06-20

428

[Report on 8 years' experience in prenatal diagnosis of genetic defects. I. Indications and methods].  

PubMed

Prenatal diagnostic procedures were done following 1231 transabdominal amniocenteses in 1113 patients of a gestational age of 17.4 +/- 0.5 weeks. Partly parallel the following methods were used: 1218 estimations of alpha-fetoprotein, 903 chromosomal analyses, 89 amniofetographies, 40 fetoscopies and 7 estaminations of hormones, immunoglobulins and enzymes. Amniotic fluid could be obtained in 91.8 per cent with the first insertion of the needle, using the free-hand-needle-technique. In 8 per cent amniotic fluid samples were bloody. The amniocentesis had to be repeated in 7.6 per cent because of no growth of cells (6.3 per cent), or no amniotic fluid could be obtained (1.3 percent). In the average 14.9 +/- 8.1 metaphases were analysed and 2.9 +/- 1.1 karyogram were made. The organisation of prenatal diagnostics was explained. The indication was in 39.6 per cent the age, in 20.3 per cent the repeated risk of the birth of a fetus with trisomy 21. In 13.7 per cent there was an indication to estimate alpha-fetoprotein which was done nearly without exception for exclusion of neural tube defects. The prenatal determination of the fetal sex was necessary in 7.3 per cent in cases of X-chromosomal inheritable diseases. Previous deliveries of infants with malformation-syndrome or chromosomal trisomies like Edwards-or Patau-syndrome and radiation or chemotherapy of one of the parents were summarized under other indications (7.3 per cent). Balanced parental translocations were the indication in 1.7 per cent. Amniofetography was used in 8 per cent of the patients to exclude malformations caused by prevalent multiple factors. It was in 35 per cent the prevailing diagnostic method. The set of problems of its use was discussed. Fetoscopy (3.6 per cent) partly was an additional diagnostic procedure partly a leading method. By means of a catalogue of indications it was referred to the use of fetoscopy to visualization in prenatal diagnostics. The exclusion of genetic metabolic defects was the motive to prenatal biochemic investigations in 0.5 per cent. The prerequisites of devices and technique to prenatal diagnostics were discussed. PMID:6198822

Weise, W; Düker, D

1983-01-01

429

Genetic diagnosis of severe myoclonic epilepsy of infancy (Dravet syndrome) with SCN1A mutations in the Hong Kong Chinese patients.  

PubMed

Epilepsy is a clinically and genetically heterogeneous group of disorders. The advent of molecular genetics brings unprecedented advancement in diagnostic molecular pathology and reduces over-reliance on traditional clinical classification. Severe myoclonic epilepsy of infancy or Dravet syndrome is a catastrophic infantile-onset epilepsy. We report two unrelated Hong Kong Chinese patients with this condition presenting with febrile seizures, epilepsy with different semiologies, psychomotor retardation, and recurrent status epilepticus. Two different mutations were characterised, viz NM_001165963.1: c.680T>G; NP_001159435.1: p.I227S and NM_001165963.1: c.3953T>G; NP_001159435.1: p.L1318R (novel). Genetic characterisation conveys a definitive diagnosis and is important from the perspective of selecting anti-epileptic drug therapy and genetic counselling. PMID:22147323

Mak, Chloe M; Chan, K Y; Yau, Eric K C; Chen, Sammy P L; Siu, W K; Law, C Y; Lam, C W; Chan, Albert Y W

2011-12-01

430

Physical mapping identifies DXS265 as a useful genetic marker for carrier detection and prenatal diagnosis of X-linked agammaglobulinemia  

Microsoft Academic Search

The gene responsible for X-linked agammaglobulinemia (XLA) has not been identified; however, in the course of genetic linkage studies designed to map the locus more precisely, a number of closely linked polymorphic loci have been identified. These have proved to be useful in identifying carriers and in pre-natal diagnosis of this disease. The DXS178 locus was found to be closest

Ruth Levering; Angela K. Sweatman; Marie-Anne J. O'Reilly; Sally A. Genet; Helen Middleton-Price; Sue Malcolm; Roland J. Levinsky; Christine Kinnon I

1993-01-01

431

Autopsy and genetic diagnosis of 21-hydroxylase deficiency with bilateral testicular tumors in a case under no medication for over one year  

Microsoft Academic Search

The autopsy findings of an adult patient with 21-hydroxylase deficiency are presented. Genetic analysis of the 21-hydroxylase gene (CYP21A2) was performed for accurate diagnosis of congenital adrenal hyperplasia (CAH), and bilateral testicular tumors were characterized. We report a 29-year-old Japanese man who was diagnosed with CAH (21-hydroxylase deficiency) in infancy and had continued steroid therapy until the age of 28.

Hajime Mizukami; Akihiko Hamamatsu; Shinjiro Mori; Shuichi Hara; Masahiko Kuroda; Tomonori Nagai; Tatsushige Fukunaga

2011-01-01

432

Conflict between values and technology: perceptions of preimplantation genetic diagnosis among women at increased risk for hereditary breast and ovarian cancer  

Microsoft Academic Search

Members of families affected by hereditary cancer are often concerned about passing on risk to offspring. Preimplantation\\u000a genetic diagnosis is a procedure performed to identify embryos that inherit mutations placing them at risk for hereditary\\u000a conditions. Little is known about attitudes toward the use of this technology among individuals at risk for hereditary breast\\u000a and ovarian cancer. We sought to

Gwendolyn P. Quinn; Susan T. Vadaparampil; Lindsey M. King; Cheryl A. Miree; Sue Friedman

2009-01-01

433

Specific detection of deleted and non-deleted dystrophin exons together with gender assignment in preimplantation genetic diagnosis of Duchenne muscular dystrophy  

Microsoft Academic Search

rates ranged from 90.2% for exon 6 to 96.7% for exons 8 and 32. At least four of the five sequences were successfully amplified in 95.8% of single cells, and sexing was possible in 98.5%. This 5-plex assay was found to be robust enough to be used in a PGD clinical procedure and was therefore applied to a family whose

A. Girardet; S. Hamamah; H. Dechaud; T. Anahory; C. Coubes; B. Hedon; J. Demaille; M. Claustres

2003-01-01

434

Genetics.  

PubMed

The present state of knowledge on the genetics of anxiety disorders, in particular panic disorder, comprising clinical and molecular genetic studies, interaction analyses, as well as meta-analyses of single association studies will be presented in detail. A particular focus will be on the most robust findings in panic disorder to date in the serotonergic, noradrenergic, and dopaminergic system, such as the catechol-O-methyltransferase (COMT) gene. Additionally, findings on the adenosine receptor 2A (A2A) gene, which has been reported to be associated with panic disorder and also with anxiety levels after caffeine administration in a gene--environment interactional model, will be discussed. Furthermore, the first imaging genetic findings in panic disorder, social phobia, and anxiety-related traits using fMRI and PET techniques in combination with molecular genetic association analyses are reviewed, taking into account the present intermediate phenotype discussion in the investigation of complex genetic disorders. Finally, the first exemplary pharmacogenetic studies in panic disorder and generalized social phobia will be presented. The pathomechanism of anxiety disorders and in particular panic disorder is considered to be multifactorial with converging evidence for a pivotal role of genetic factors in particular, which will be presented in detail in this chapter. PMID:21309106

Domschke, Katharina; Deckert, Jürgen

2010-01-01

435

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

436

Balance Between PGD Synthase and PGE Synthase Is a Major Determinant of Atherosclerotic Plaque Instability in Humans  

Microsoft Academic Search

Objective—Inducible cyclooxygenase (COX-2) catalyzes the first step in prostanoid biosynthesis and is considered a proinflammatory enzyme. COX-2 and type 1 inducible PGE synthase (mPGES-1) have a role in metalloproteinase (MMP) release leading to plaque rupture. In contrast, lipocalin-type PGD synthase (L-PGDS) has been shown to exert antiinflammatory actions. Thus, in this study we investigated whether a shift from a PGDS-oriented

Francesco Cipollone; Maria Fazia; Annalisa Iezzi; Giovanni Ciabattoni; Barbara Pini; Chiara Cuccurullo; Sante Ucchino; Francesco Spigonardo; Mariella De Luca; Cesaria Prontera; Francesco Chiarelli; Franco Cuccurullo; Andrea Mezzetti

2010-01-01

437

BRIEF REVIEW Application of Molecular Genetics to Prenatal Diagnosis and Carrier Detection in the Hemophilias: Some Limitations  

Microsoft Academic Search

Prenatal diagnosis and carrier detection in the hemophilias have received much attention in recent years. The error rate in prenatal diagnosis by fetoscopy is <1 %; fetoscopy is not possible, however, until the second trimester of preg- nancy. Carrier detection based on bioassays of plasma has an irreducible error rate (-5%?), because of the \\

John B. Graham; Philip P. Green; Royal A. McGraw; Lisa M. Davis

1985-01-01

438

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

439

Genetic Diagnosis of Familial Hypercholesterolemia in a South European Outbreed Population: Influence of Low Density Lipoprotein (LDL) Receptor Gene Mutations on Treatment Response to Simvastatin in Total, LDL, and High-Density Lipoprotein Cholesterol  

Microsoft Academic Search

The aims of this study were to examine the presence of mu- tations in the low-density lipoprotein receptor gene among subjects clinically diagnosed with familial hypercholesterol- emia and to analyze whether the molecular diagnosis helps to predict the response to simvastatin treatment in our familial hypercholesterolemia population. Fifty-five probands and 128 related subjects with familial hypercholesterolemia were studied. Genetic diagnosis

FELIPE J. CHAVES; ANA B. GARCIA-GARCIA; MIGUEL CIVERA; MARIA E. ARMENGOD; JUAN F. ASCASO; RAFAEL CARMENA