Genotype-first in a cohort of 95 fetuses with multiple congenital abnormalities: when exome sequencing reveals unexpected fetal phenotype-genotype correlations.

Fiche publication

Date publication

juillet 2020

Journal

Journal of medical genetics

Auteurs

Membres identifiés du Cancéropôle Est :
Pr GAILLARD Dominique , Pr MANDEL Jean-Louis , Pr FAIVRE Laurence , Pr PHILIPPE Christophe , Dr NAMBOT Sophie , Pr LEBRE Anne-Sophie , Pr THAUVIN-ROBINET Christel , Pr KUENTZ Paul

Tous les auteurs :
Lefebvre M, Bruel AL, Tisserant E, Bourgon N, Duffourd Y, Collardeau-Frachon S, Attie-Bitach T, Kuentz P, Assoum M, Schaefer E, El Chehadeh S, Antal MC, Kremer V, Girard-Lemaitre F, Mandel JL, Lehalle D, Nambot S, Jean-Marçais N, Houcinat N, Moutton S, Marle N, Lambert L, Jonveaux P, Foliguet B, Mazutti JP, Gaillard D, Alanio E, Poirisier C, Lebre AS, Aubert-Lenoir M, Arbez-Gindre F, Odent S, Quélin C, Loget P, Fradin M, Willems M, Bigi N, Perez MJ, Blesson S, Francannet C, Beaufrere AM, Patrier-Sallebert S, Guerrot AM, Goldenberg A, Brehin AC, Lespinasse J, Touraine R, Capri Y, Saint-Frison MH, Laurent N, Philippe C, Tran Mau-Them F, Thevenon J, Faivre L, Thauvin-Robinet C, Vitobello A

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/32732226

Résumé

Molecular diagnosis based on singleton exome sequencing (sES) is particularly challenging in fetuses with multiple congenital abnormalities (MCA). Indeed, some studies reveal a diagnostic yield of about 20%, far lower than in live birth individuals showing developmental abnormalities (30%), suggesting that standard analyses, based on the correlation between clinical hallmarks described in postnatal syndromic presentations and genotype, may underestimate the impact of the genetic variants identified in fetal analyses.