Fluorescent PCR and automated fragment analysis for the clinical application of preimplantation genetic diagnosis of myotonic dystrophy (Steinert's disease)

Sermon, Karen; Vos, Anick De; Velde, H. Van de; Seneca, Sara; Lissens, Willy; Joris, Hubert; Vandervorst, M.; Steirteghem, A. Van; Liebaers, Ingeborg

doi:10.1093/molehr/4.8.791

Cited by 96 publications

(62 citation statements)

References 14 publications

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“…The first single cell assay developed for PGD DM1 allowed the selection of "unaffected" embryos based on the presence in the biopsied cell of the "normal CTG repeat" of the affected partner and on the "normal CTG repeat" of the unaffected partner [9,10]. Initially only fully informative couples i.e.…”

Section: Genetic Testing With a View To Performing Pgdmentioning

confidence: 99%

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The reproductive outcome of female patients with myotonic dystrophy type 1 (DM1) undergoing PGD is not affected by the size of the expanded CTG repeat tract

Verpoest

Seneca

Rademaeker

et al. 2010

J Assist Reprod Genet

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Purpose This study aims to analyze the relationship between trinucleotide repeat length and reproductive outcome in a large cohort of DM1 patients undergoing ICSI and PGD. Methods Prospective cohort study. The effect of trinucleotide repeat length on reproductive outcome per patient was analyzed using bivariate analysis (T-test) and multivariate analysis using Kaplan-Meier and Cox regression analysis. Results Between 1995 and 2005, 205 cycles of ICSI and PGD were carried out for DM1 in 78 couples. The number of trinucleotide repeats does not have an influence on reproductive outcome when adjusted for age, BMI, basal FSH values, parity, infertility status and male or female affected. Cox regression analysis indicates that cumulative live birth rate is not influenced by the number of trinucleotide repeats. The only factor with a significant effect is age (p<0.05). Conclusion There is no evidence of an effect of trinucleotide repeat length on reproductive outcome in patients undergoing ICSI and PGD.

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Section: Genetic Testing With a View To Performing Pgdmentioning

confidence: 99%

“…For semi-informative couples or not informative couples the Triplet-Primed PCR (TP-PCR) protocol was applied. A conclusive diagnosis of an unaffected embryo was assigned only if and when two blastomeres gave the same unaffected result for the disorder [10,12].…”

Section: Genetic Diagnosis In Blastomeresmentioning

confidence: 99%

The reproductive outcome of female patients with myotonic dystrophy type 1 (DM1) undergoing PGD is not affected by the size of the expanded CTG repeat tract

Verpoest

Seneca

Rademaeker

et al. 2010

J Assist Reprod Genet

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“…The first single cell polymerase chain reaction (PCR) assay developed for PGD-DM1 allowed selection of unaffected embryos based on the presence of the 'normal repeat' of the affected and one of the repeats of the unaffected partner in the biopsied cell. 8,12 As the expanded repeat of the affected parent cannot be amplified by conventional PCR at the single cell level, only fully informative couples, with the normal allele of the affected partner clearly different from the alleles of the unaffected partner, were eligible for PGD. From 1997 onwards, with the development of the triplet-primed PCR (TP-PCR) based test, half-informative couples with both partners sharing one allele size and non-informative couples with three identical normal alleles, could also be offered treatment.…”

Section: 11mentioning

confidence: 99%

“…At first, a nested PCR approach was taken, but this was later replaced by fluorescent PCR techniques. 8,12 For half-informative or non-informative couples, a TP-PCR procedure was performed.…”

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confidence: 99%

Preimplantation genetic diagnosis for myotonic dystrophy type 1: upon request to child

et al. 2009

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Preimplantation genetic diagnosis (PGD) is an alternative to prenatal diagnosis for patients at risk of transmitting an inherited disease such as myotonic dystrophy type 1(DM1) to their offspring. In this paper, the clinical application of preimplantation diagnosis for DM1 upon request to children born is described in a large cohort of risk couples. PGD could be offered to all 78 couples opting for PGD regardless of the triplet repeat size. The incidence of major complications was minimalised following a careful assessment in affected DM1 females anticipating possible cardiological, obstetrical and anaesthetical problems. A livebirth delivery rate per cycle with oocyte retrieval of 20% was the outcome. Forty-eight of the 49 children born are in good health and have normal psychomotor development.

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“…Since the large expanded alleles are refractive to PCR amplification, a general approach, allowing detection of only healthy alleles, was applied. The PGD strategy involved amplification of the DNA fragment around the repeated region and STR markers linked to this region for ADO detection (Sermon et al, 1998;Dean et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Preimplantation Genetic Diagnosis for Single Gene Disorders

Fiorentine¹

Practical Preimplantation Genetic Diagnosis

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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 for SGDs were performed in combination with HLA matching. The strategy in each case used an initial multiplex PCR, followed by minisequencing to identify the mutation(s) combined with multiplex PCR for closely linked informative markers to increase accuracy. Linkage analysis, using intragenic and/or extragenic polymorphic microsatellite markers, was performed in cases where the disease-causing mutation(s) was unknown or undetectable. RESULTS: In 250 PGD cycles, a total of 1961 cleavage stage embryos were biopsied. PCR was successful in 3409 out of 3149 (92.4%) biopsied blastomeres and a diagnosis was possible in 1849 (94.3%) embryos. Four hundred and twenty-seven embryos were transferred in 211 cycles, resulting in 71 pregnancies (33.6% per embryo transfer), including 15 biochemical pregnancies, six spontaneous miscarriages, two ectopic pregnancies, which were terminated, and nine pregnancies which are still ongoing. The remaining pregnancies were confirmed to be unaffected and went to term without complications, resulting in the birth of 35 healthy babies. CONCLUSIONS: Minisequencing for mutation detection combined with multiplex fluorescence PCR for linkage analysis is an efficient, accurate and widely applicable strategy for PGD of SGDs. Our experience provides a further demonstration that PGD is an effective clinical tool and a useful option for many couples with a high risk of transmitting a genetic disease.

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Fluorescent PCR and automated fragment analysis for the clinical application of preimplantation genetic diagnosis of myotonic dystrophy (Steinert's disease)

Cited by 96 publications

References 14 publications

The reproductive outcome of female patients with myotonic dystrophy type 1 (DM1) undergoing PGD is not affected by the size of the expanded CTG repeat tract

The reproductive outcome of female patients with myotonic dystrophy type 1 (DM1) undergoing PGD is not affected by the size of the expanded CTG repeat tract

Preimplantation genetic diagnosis for myotonic dystrophy type 1: upon request to child

Preimplantation Genetic Diagnosis for Single Gene Disorders

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