Preimplantation genetic diagnosis for myotonic dystrophy type 1 in the UK

Kakourou, Georgia; Dhanjal, Seema; Mamas, T; Gotts, Sarah; Doshi, Alpesh; Fordham, Karen; Serhal, Paul; Ranieri, Domenico Massimo; Delhanty, Joy D. A.; Harper, Joyce; SenGupta, Sioban

doi:10.1016/j.nmd.2007.10.002

Cited by 23 publications

(22 citation statements)

References 19 publications

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“…PGD (preimplantation genetic diagnosis) for FSHD is performed by linkage analysis or by known D4Z4 (shortened) repeat size at even fewer centers in the world (4 centers were listed in 2007, after which the website ceased to list which labs offer PGD for specific genetic diseases). PGD is currently being performed for DMD and Myotonic Dystrophy, both of which are more severe phenotypically than FSHD (Harper et al 2001;Kakourou et al 2008;Malcov et al 2005). In our study, individuals interested in PND from 4 families were tested and/or counseled for FSHD.…”

Section: Discussionmentioning

confidence: 99%

Genetic Counseling and Testing for FSHD (Facioscapulohumeral Muscular Dystrophy) in the Israeli Population

Yanoov-Sharav

Leshinsky‐Silver

Cohen

et al. 2011

Journal of Genetic Counseling

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Facioscapulohumeral muscular dystrophy (FSHD), is a dominantly inherited, late onset, progressive disease. At present, no treatment or prevention of symptoms are available. There is considerable clinical variability, even within families. The gene whose defect causes FSHD has not been identified, but molecular diagnosis can be made by analyzing D4Z4 repeat length on chromosome 4q35. The results can support or rule out the clinical diagnosis of FSHD, but there are also "gray zone", non-conclusive results. During the years 2000-6, 66 individuals (including 7 asymptomatic individuals), were tested in our institute for D4Z4 repeat number. In 77% of the cases the results were conclusive: two thirds of them supported a diagnosis of FSHD while in a third this diagnosis was ruled out. In 23% the results were in the gray zone. Cognitive involvement was rare, occurring only when the D4Z4 repeat size was very small (<15 kb). Maximal utilization of the existing molecular test for FSHD demands detailed clinical and family pedigree information. We recommend that comprehensive genetic counseling always be given before and after molecular testing for FSHD, in addition to the neurological follow-up. Presymptomatic testing should only be offered when complete molecular evaluation can be offered, including 4qA and 4qB variant analysis.

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Section: Discussionmentioning

confidence: 99%

Genetic Counseling and Testing for FSHD (Facioscapulohumeral Muscular Dystrophy) in the Israeli Population

Yanoov-Sharav

Leshinsky‐Silver

Cohen

et al. 2011

Journal of Genetic Counseling

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“…The TP-PCR protocol was used for PGD for all patients who were uninformative for the DMPK locus and/or the linked polymorphic markers, as previously described elsewhere (16).…”

Section: Materials and Methods Pgd Protocol Workupmentioning

confidence: 99%

“…The IVF treatment, embryo biopsy procedure, and lysis of single cells were performed as previously described elsewhere (16,18). Two blastomeres were removed from all embryos with six or more cells on day 3, and one blastomere was removed from embryos with five cells or less.…”

Section: Ivf and Embryo Biopsy Proceduresmentioning

confidence: 99%

“…For couples who are informative for DMPK but uninformative for markers linked to the DMPK gene, where the phase cannot be established, unlinked markers have also been used for contamination detection, whereas for couples who are uninformative or semiinformative for both the DMPK region and the linked markers tested, another protocol known as triplet repeat primed polymerase chain reaction (TP-PCR) is used in PGD of DM1 to differentiate between the homozygous unaffected and affected genotypes (15)(16)(17).…”

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confidence: 99%

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Modification of the triplet repeat primed polymerase chain reaction method for detection of the CTG repeat expansion in myotonic dystrophy type 1: application in preimplantation genetic diagnosis

Kakourou

Dhanjal

Mamas

et al. 2010

Fertility and Sterility

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“…Diagnosis of normal embryos is based upon the PCR amplification of two alleles with repeat sizes in normal range. Affected embryos only have one allele that amplifies by PCR (Kakourou et al 2008). If the couple are not informative for the triplet repeat (have the same number of triplet repeats for their normal alleles) and are also not informative for linked markers, then triple-primed PCR can be used to amplify the expanded repeat to distinguish embryos with an expansion from those that are transferable (Kakourou et al 2010).…”

Section: Molecular Diagnosismentioning

confidence: 99%

Preimplantation genetic diagnosis: State of the ART 2011

2011

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For the last 20 years, preimplantation genetic diagnosis (PGD) has been mostly performed on cleavage stage embryos after the biopsy of 1-2 cells and PCR and FISH have been used for the diagnosis. The main indications have been single gene disorders and inherited chromosome abnormalities. Preimplantation genetic screening (PGS) for aneuploidy is a technique that has used PGD technology to examine chromosomes in embryos from couples undergoing IVF with the aim of helping select the chromosomally 'best' embryo for transfer. It has been applied to patients of advanced maternal age, repeated implantation failure, repeated miscarriages and severe male factor infertility. Recent randomised controlled trials (RCTs) have shown that PGS performed on cleavage stage embryos for a variety of indications does not improve delivery rates. At the cleavage stage, the cells biopsied from the embryo are often not representative of the rest of the embryo due to chromosomal mosaicism. There has therefore been a move towards blastocyst and polar body biopsy, depending on the indication and regulations in specific countries (in some countries, biopsy of embryos is not allowed). Blastocyst biopsy has an added advantage as vitrification of blastocysts, even post biopsy, has been shown to be a very successful method of cryopreserving embryos. However, mosaicism is also observed in blastocysts. There have been dramatic changes in the method of diagnosing small numbers of cells for PGD. Both array-comparative genomic hybridisation and single nucleotide polymorphism arrays have been introduced clinically for PGD and PGS. For PGD, the use of SNP arrays brings with it ethical concerns as a large amount of genetic information will be available from each embryo. For PGS, RCTs need to be conducted using both array-CGH and SNP arrays to determine if either will result in an increase in delivery rates.

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Preimplantation genetic diagnosis for myotonic dystrophy type 1 in the UK

Cited by 23 publications

References 19 publications

Genetic Counseling and Testing for FSHD (Facioscapulohumeral Muscular Dystrophy) in the Israeli Population

Genetic Counseling and Testing for FSHD (Facioscapulohumeral Muscular Dystrophy) in the Israeli Population

Modification of the triplet repeat primed polymerase chain reaction method for detection of the CTG repeat expansion in myotonic dystrophy type 1: application in preimplantation genetic diagnosis

Preimplantation genetic diagnosis: State of the ART 2011

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