PGD for de novo mutation: when mosaicism prevents PGD setup and leads to genetic counselling revision

Introduction: In our centre, due to legal restrictions precluding the use of whole genome analyses, PGD for monogenic disorders with de novo mutation is based on multiplex PCR combining direct and indirect diagnosis of single blastomeres. Haplotypes can be either deduced from single sperm, or polar bodies, or during embryo analysis. For clivage-stage PGD, setup is performed and validated on series of single cells. In case of mosaicism, at risk haplotype is present in cells with, but also without, mutation and allele drop out (ADO) cannot be properly evaluated. Due to ADO possibility, only embryos with the normal haplotype are considered for transfer. We present issues and consequences of PGD setup in a case referred for tuberous sclerosis with mosaicism in the male partner.