Premium
Next‐generation sequencing in a series of 80 fetuses with complex cardiac malformations and/or heterotaxy
Author(s) -
Liu Hui,
GiguetValard AnnaGaëlle,
Simonet Thomas,
SzenkerRavi Emmanuelle,
Lambert Laetitia,
VincentDelorme Catherine,
Scheidecker Sophie,
Fradin Mélanie,
MoricePicard Fanny,
Naudion Sophie,
CiornaMonferrato Viorica,
Colin Estelle,
Fellmann Florence,
Blesson Sophie,
Jouk PierreSimon,
Francannet Christine,
Petit Florence,
Moutton Sébastien,
Lehalle Daphné,
Chassaing Nicolas,
El Zein Loubna,
Bazin Anne,
Bénéteau Claire,
AttiéBitach Tania,
Hanu Sylvie M.,
Brechard MariePierre,
Chiesa Jean,
Pasquier Laurent,
Rooryck Caroline,
Van Maldergem Lionel,
Cabrol Christelle,
El Chehadeh Salima,
Vasiljevic Alexandre,
Isidor Bertrand,
Abel Carine,
Theve Julien,
Di Filippo Sylvie,
VigourouxCastera 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
Publication year - 2020
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.24132
Subject(s) - heterotaxy , biology , fetus , consanguinity , medicine , genetics , pregnancy , heart disease
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.