title: 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.affiliation: 1] Unité Université Paris Descartes-Sorbonne Paris Cité, Institut imagine, INSERM-U781, Paris, France [2] Service de génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Steffann
authors.affiliation: 1] Unité Université Paris Descartes-Sorbonne Paris Cité, Institut imagine, INSERM-U781, Paris, France [2] Service de génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Michot
authors.affiliation: 1] Unité Université Paris Descartes-Sorbonne Paris Cité, Institut imagine, INSERM-U781, Paris, France [2] Service de génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France.
authors.forename: Roxana
authors.initials: R
authors.lastname: Borghese
authors.affiliation: 1] Unité Université Paris Descartes-Sorbonne Paris Cité, Institut imagine, INSERM-U781, Paris, France [2] Service de génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France.
authors.forename: Marcia
authors.initials: M
authors.lastname: Baptista-Fernandes
authors.affiliation: 1] Unité Université Paris Descartes-Sorbonne Paris Cité, Institut imagine, INSERM-U781, Paris, France [2] Service de génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Monnot
authors.affiliation: 1] Unité Université Paris Descartes-Sorbonne Paris Cité, Institut imagine, INSERM-U781, Paris, France [2] Service de génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bonnefont
authors.affiliation: 1] Unité Université Paris Descartes-Sorbonne Paris Cité, Institut imagine, INSERM-U781, Paris, France [2] Service de génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France.
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
mesh_terms: D000328:Adult; D005260:Female; D005799:Genes, Dominant; D030342:Genetic Diseases, Inborn / Q000175:diagnosis* / Q000235:genetics*; D005820:Genetic Testing; D006223:Hamartoma Syndrome, Multiple / Q000175:diagnosis / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D009030:Mosaicism; D051059:PTEN Phosphohydrolase / Q000235:genetics; D010375:Pedigree; D011247:Pregnancy; D019836:Preimplantation Diagnosis
chemical_list: D051059:PTEN Phosphohydrolase
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