作者
Hui Liu,Anna‐Gaëlle Giguet‐Valard,Thomas Simonet,Emmanuelle Szenker‐Ravi,Laëtitia Lambert,Catherine Vincent-Delormé,Sophie Scheidecker,Mélanie Fradin,Fanny Morice‐Picard,Sophie Naudion,Viorica Ciorna‐Monferrato,Estelle Colin,Florence Fellmann,Sophie Blesson,Pierre‐Simon Jouk,Christine Francannet,Florence Petit,Sébastien Moutton,Daphné Lehalle,Nicolas Chassaing,Loubna El Zein,Anne Bazin,Claire Bénéteau,Tania Attié‐Bitach,Sylvie Manouvrier Hanu,Marie-Pierre Bréchard,Jean Chiésa,Laurent Pasquier,Caroline Rooryck,Lionel Van Maldergem,Christelle Cabrol,Salima El Chehadeh,Alexandre Vasiljevic,Bertrand Isidor,C. Abel,Julien Thévenon,Sylvie Di Filippo,Adeline Vigouroux‐Castera,Jocelyne Attia,Chloé Quēlin,Sylvie Odent,Juliette Piard,Fabienne Giuliano,Audrey Putoux,Philippe Khau Van Kien,Catherine Yardin,Renaud Touraine,Bruno Reversade,Patrice Bouvagnet
摘要
Herein, we report the screening of a large panel of genes in a series of 80 fetuses with congenital heart defects (CHDs) and/or heterotaxy and no cytogenetic anomalies. There were 49 males (61%/39%), with a family history in 28 cases (35%) and no parental consanguinity in 77 cases (96%). All fetuses had complex CHD except one who had heterotaxy and midline anomalies while 52 cases (65%) had heterotaxy in addition to CHD. Altogether, 29 cases (36%) had extracardiac and extra-heterotaxy anomalies. A pathogenic variant was found in 10/80 (12.5%) cases with a higher percentage in the heterotaxy group (8/52 cases, 15%) compared with the non-heterotaxy group (2/28 cases, 7%), and in 3 cases with extracardiac and extra-heterotaxy anomalies (3/29, 10%). The inheritance was recessive in six genes (DNAI1, GDF1, MMP21, MYH6, NEK8, and ZIC3) and dominant in two genes (SHH and TAB2). A homozygous pathogenic variant was found in three cases including only one case with known consanguinity. In conclusion, after removing fetuses with cytogenetic anomalies, next-generation sequencing discovered a causal variant in 12.5% of fetal cases with CHD and/or heterotaxy. Genetic counseling for future pregnancies was greatly improved. Surprisingly, unexpected consanguinity accounts for 20% of cases with identified pathogenic variants.