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

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...

Full description

Saved in:
Bibliographic Details
Published in:Human mutation 2020-12, Vol.41 (12), p.2167-2178
Main 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‐Thambo, 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
Format: Article
Language:English
Subjects:
congenital heart defects
Consanguinity
Cytogenetics
fetus
Fetuses
Genetic counseling
Genetics
Heredity
heterotaxy
Human genetics
Life Sciences
midline anomaly
next‐generation sequencing
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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.
ISSN:1059-7794
1098-1004
DOI:10.1002/humu.24132