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

Fiorentino, Francesco; Biricik, Anıl; Nuccitelli, Andrea; Palma, R. De; Kahraman, Semra; Iacobelli, Marcello; Trengia, Vincenzo; Caserta, Donatella; Bonu, M.A.; Borini, Andrea; Baldi, Marina

doi:10.1093/humrep/dei382

Cited by 96 publications

(71 citation statements)

References 51 publications

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“…Data showed that the second most frequent cause of FP diagnosis was ADO, an inherent pitfall of single-cell PCR. Strategies to overcome the technical limitations of single-cell PCR have been previously described 4,[16][17][18] and incorporated in the ESHRE best practice guidelines for monogenic PGD. 7 To preclude adverse misdiagnosis due to ADO and contamination, the co-amplification of linked polymorphic markers across the locus of interest is highly recommended and the advantages of the approach had been extensively described.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of PCR-based preimplantation genetic diagnosis applied to monogenic diseases: a collaborative ESHRE PGD consortium study

et al. 2013

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Preimplantation genetic diagnosis (PGD) for monogenic disorders currently involves polymerase chain reaction (PCR)-based methods, which must be robust, sensitive and highly accurate, precluding misdiagnosis. Twelve adverse misdiagnoses reported to the ESHRE PGD-Consortium are likely an underestimate. This retrospective study, involving six PGD centres, assessed the validity of PCR-based PGD through reanalysis of untransferred embryos from monogenic-PGD cycles. Data were collected on the genotype concordance at PGD and follow-up from 940 untransferred embryos, including details on the parameters of PGD cycles: category of monogenic disease, embryo morphology, embryo biopsy and genotype assay strategy. To determine the validity of PCR-based PGD, the sensitivity (Se), specificity (Sp) and diagnostic accuracy were calculated. Stratified analyses were also conducted to assess the influence of the parameters above on the validity of PCR-based PGD. The analysis of overall data showed that 93.7% of embryos had been correctly classified at the time of PGD, with Se of 99.2% and Sp of 80.9%. The stratified analyses found that diagnostic accuracy is statistically significantly higher when PGD is performed on two cells versus one cell (P ¼ 0.001). Se was significantly higher when multiplex protocols versus singleplex protocols were applied (P ¼ 0.005), as well as for PGD applied on cells from good compared with poor morphology embryos (P ¼ 0.032). Morphology, however, did not affect diagnostic accuracy. Multiplex PCR-based methods on one cell, are as robust as those on two cells regarding false negative rate, which is the most important criteria for clinical PGD applications. Overall, this study demonstrates the validity, robustness and high diagnostic value of PCR-based PGD.

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Section: Discussionmentioning

confidence: 99%

Evaluation of PCR-based preimplantation genetic diagnosis applied to monogenic diseases: a collaborative ESHRE PGD consortium study

et al. 2013

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“…It has proven to be accurate enough to detect single nucleotide substitutions in the context of PGD [24,25]. This technique allows us to interrogate the exact position of a nucleotide change, genotyping the embryo.…”

Section: Discussionmentioning

confidence: 99%

Preimplantation genetic diagnosis of P450 oxidoreductase deficiency and Huntington Disease using three different molecular approaches simultaneously

Alberola

Bautista-Llácer

Fernández

et al. 2009

J Assist Reprod Genet

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“…As performing PGD, two blastomeres can be examined from one embryo at the same time, providing a double check for the results. It was reported that pregnancy and implantation rates did not appear to be significantly affected in spite of the biopsy of the two cells from embryos with 7 or more cells [31]. When the results of both blastomeres are identically normal, there is a high probability that the embryo will also be normal.…”

Section: Discussionmentioning

confidence: 99%

“…The distribution is wider in patient's lymphocytes: some of the patient's lymphocytes were categorized as normal contrary to expectations. These results may be due to PCR amplification failure in duplicated exons in the same way as the phenomenon that results in the failure to amplify one allele of a heterozygous locus, commonly called allele drop-out, of which the rate ranges from 0 to 12.9% with the average rate taken to be 7.5% [31]. Amplification failure, which is a dangerous risk in PCR from single cells, can lead to a misdiagnosis, especially in gender determination.…”

Section: Discussionmentioning

confidence: 99%

Well-devised quantification analysis for duplication mutation of Duchenne muscular dystrophy aimed at preimplantation genetic diagnosis

Nakabayashi

Sueoka

Tajima

et al. 2007

J Assist Reprod Genet

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Purpose: Preimplantation genetic diagnosis (PGD) has been performed for deletion and point mutation type of Duchenne muscular dystrophy (DMD). Our aim was to develop a PGD technique, not yet established, to directly detect duplication mutation instead of substitute diagnosis similar to gender determination.Methods: Our method is based on comparative quantification using conventional duplex PCR, real-time PCR and gender determination. We evaluated this method in single lymphocytes from a duplication type of DMD patient and a normal male.Results: There was a significant difference in the mean values of the ratios (the mutation locus/a normal reference): mean value ± SE was 1.84 ± 0.15 in the duplication patient, and 1.00 ± 0.09 in the normal male (p < 0.001).Conclusion: It is suggested that our comparative quantification method could be a new option in PGD for carriers with duplication mutation who wish to have an unaffected son.

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

Cited by 96 publications

References 51 publications

Evaluation of PCR-based preimplantation genetic diagnosis applied to monogenic diseases: a collaborative ESHRE PGD consortium study

Evaluation of PCR-based preimplantation genetic diagnosis applied to monogenic diseases: a collaborative ESHRE PGD consortium study

Preimplantation genetic diagnosis of P450 oxidoreductase deficiency and Huntington Disease using three different molecular approaches simultaneously

Well-devised quantification analysis for duplication mutation of Duchenne muscular dystrophy aimed at preimplantation genetic diagnosis

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