Feasibility Study of Preimplantation Genetic Diagnosis for Single-gene Disorders

Feasibility Study of Preimplantation Genetic Diagnosis for Single-gene Disorders by Using Nextgeneration Sequencing

Preimplantation Genetic Diagnosis (PGD) for monogenic diseases is usually performed by multiplex PCR combining polymorphic microsatellites familial analysis and, where possible, couple-specific mutation detection. Single-cell multiplex PCR developments are costly and time-consuming. We propose to test and clinically validate a targeted next-generation sequencing approach for the PGD for cystic fibrosis. This technique would allow a PGD for probably almost every couple asking for it in our centre, without a previous couple-specific development (but only a preliminary familial analysis). It will be based on haplotyping using a large number of SNPs and mutation detection. A clinical validation will be performed by reanalysing non-transferable embryos obtained after PGD for cystic fibrosis, with couple's informed consent. Concordance of the results between PGD and reanalysis by NGS will be achieved and if validated, this technique may be applied to future PGD for cystic fibrosis in our centre. The same technique may then be applied for other PGD indications for which a set-up is often needed.

Inclusion Criteria:

• Age> or = 18 years

• Couples at risk of transmitting cystic fibrosis

• asking for a PGD in Strasbourg

• DNA samples available at the laboratory for:

  • The couple
  • A related with CFTR status known
  • Having signed an informed consent

Exclusion Criteria:

• Inability to give informed consent (understanding difficulties...)