Parental mosaicism is a pitfall in preimplantation genetic diagnosis of dominant disorders.

Abstract

PCR amplification on single cells is prone to allele drop-out (PCR failure of one allele), a cause of misdiagnosis in preimplantation genetic diagnosis (PGD). Owing to this error risk, PGD usually relies on both direct and indirect genetic analyses. When the affected partner is the sporadic case of a dominant disorder, building haplotypes require spermatozoon or polar body testing prior to PGD, but these procedures are cost and time-consuming. A couple requested PGD because the male partner suffered from a dominant Cowden syndrome (CS). He was a sporadic case, but the couple had a first unaffected child and the non-mutated paternal haplotype was tentatively deduced. The couple had a second spontaneous pregnancy and the fetus was found to carry the at-risk haplotype but not the PTEN mutation. The mutation was present in blood from the affected father, but at low level, confirming the somatic mosaicism. Ignoring the possibility of mosaicism in the CS patient would have potentially led to selection of affected embryos. This observation emphasizes the risk of PGD in families at risk to transmit autosomal-dominant disorder when the affected partner is a sporadic case.

• Authors: Julie Steffann, Caroline Michot, Roxana Borghese, Marcia Baptista-Fernandes, Sophie Monnot, Jean-Paul Bonnefont, Arnold Munnich
• Journal: European journal of human genetics : EJHG (Eur J Hum Genet) Vol. 22 Issue 5 Pg. 711-2 (May 2014) ISSN: 1476-5438 [Electronic] England
• PMID: 24022303 (Publication Type: Journal Article)

Chemical References

• PTEN Phosphohydrolase

Topics

• Adult
• Female
• Genes, Dominant
• Genetic Diseases, Inborn (diagnosis, genetics)
• Genetic Testing
• Hamartoma Syndrome, Multiple (diagnosis, genetics)
• Haplotypes
• Humans
• Male
• Mosaicism
• PTEN Phosphohydrolase (genetics)
• Pedigree
• Pregnancy
• Preimplantation Diagnosis