Next-generation sequencing in a series of 80 fetuses with complex cardiac malformations and/or heterotaxy

Hui Liu, Anna Gaëlle Giguet-Valard, Thomas Simonet, Emmanuelle Szenker-Ravi, Laetitia Lambert, Catherine Vincent-Delorme, 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 ChassaingLoubna El Zein, Anne Bazin, Claire Bénéteau, Tania Attié-Bitach, Sylvie M. Hanu, Marie Pierre Brechard, Jean Chiesa, Laurent Pasquier, Caroline Rooryck-Thambo, Lionel Van Maldergem, Christelle Cabrol, Salima El Chehadeh, Alexandre Vasiljevic, Bertrand Isidor, Carine Abel, Julien Thevenon, Sylvie Di Filippo, Adeline Vigouroux-Castera, Jocelyne Attia, Chloé Quelin, Sylvie Odent, Juliette Piard, Fabienne Giuliano, Audrey Putoux, Philippe Khau Van Kien, Catherine Yardin, Renaud Touraine, Bruno Reversade, Patrice Bouvagnet

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.
Original languageEnglish (US)
Pages (from-to)2167-2178
Number of pages12
JournalHuman mutation
Issue number12
StatePublished - Dec 1 2020
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2023-02-15

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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