Next‐generation sequencing in a series of 80 fetuses with complex cardiac malformations and/or heterotaxy. Issue 12 (10th November 2020)

• Record Type: Journal Article
• Authors: Liu, Hui; Giguet‐Valard, Anna‐Gaëlle; Simonet, Thomas; Szenker‐Ravi, Emmanuelle; Lambert, Laetitia; Vincent‐Delorme, Catherine; Scheidecker, Sophie; Fradin, Mélanie; Morice‐Picard, Fanny; Naudion, Sophie; Ciorna‐Monferrato, Viorica; Colin, Estelle; Fellmann, Florence; Blesson, Sophie; Jouk, Pierre‐Simon; Francannet, Christine; Petit, Florence; Moutton, Sébastien; Lehalle, Daphné; Chassaing, Nicolas; El Zein, Loubna; Bazin, Anne; Bénéteau, Claire; Attié‐Bitach, Tania; Hanu, Sylvie M.; Brechard, Marie‐Pierre; Chiesa, Jean; Pasquier, Laurent; Rooryck, Caroline; Van Maldergem, Lionel; Cabrol, Christelle; El Chehadeh, Salima; Vasiljevic, Alexandre; Isidor, Bertrand; Abel, Carine; Thevenon, Julien; Di Filippo, Sylvie; Vigouroux‐Castera, Adeline; Attia, Jocelyne; Quelin, Chloé; Odent, Sylvie; Piard, Juliette; Giuliano, Fabienne; Putoux, Audrey; Khau Van Kien, Philippe; Yardin, Catherine; Touraine, Renaud; Reversade, Bruno; Bouvagnet, Patrice;
• Is Part Of: Human mutation. Volume 41:Issue 12(2020)
• Page Start: 2167
• Page End: 2178
• Publication Date: 2020-11-10
• Subjects: congenital heart defects -- consanguinity -- fetus -- heterotaxy -- midline anomaly -- next‐generation sequencing; Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.24132
• Languages: English
• ISSNs: 1059-7794

Abstract

Abstract: 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. Abstract : This figure shows the number of fetuses with causal variants identified in a cohort of 80 cases with congenital heart defects and/or heterotaxy after sequencing their DNA by next‐generation sequencing with a large panel of cardiac genes.