TY - JOUR
T1 - Next-generation sequencing in a series of 80 fetuses with complex cardiac malformations and/or heterotaxy
AU - Liu, Hui
AU - Giguet-Valard, Anna Gaëlle
AU - Simonet, Thomas
AU - Szenker-Ravi, Emmanuelle
AU - Lambert, Laetitia
AU - Vincent-Delorme, Catherine
AU - Scheidecker, Sophie
AU - Fradin, Mélanie
AU - Morice-Picard, Fanny
AU - Naudion, Sophie
AU - Ciorna-Monferrato, Viorica
AU - Colin, Estelle
AU - Fellmann, Florence
AU - Blesson, Sophie
AU - Jouk, Pierre Simon
AU - Francannet, Christine
AU - Petit, Florence
AU - Moutton, Sébastien
AU - Lehalle, Daphné
AU - Chassaing, Nicolas
AU - El Zein, Loubna
AU - Bazin, Anne
AU - Bénéteau, Claire
AU - Attié-Bitach, Tania
AU - Hanu, Sylvie M.
AU - Brechard, Marie Pierre
AU - Chiesa, Jean
AU - Pasquier, Laurent
AU - Rooryck-Thambo, Caroline
AU - Van Maldergem, Lionel
AU - Cabrol, Christelle
AU - El Chehadeh, Salima
AU - Vasiljevic, Alexandre
AU - Isidor, Bertrand
AU - Abel, Carine
AU - Thevenon, Julien
AU - Di Filippo, Sylvie
AU - Vigouroux-Castera, Adeline
AU - Attia, Jocelyne
AU - Quelin, Chloé
AU - Odent, Sylvie
AU - Piard, Juliette
AU - Giuliano, Fabienne
AU - Putoux, Audrey
AU - Khau Van Kien, Philippe
AU - Yardin, Catherine
AU - Touraine, Renaud
AU - Reversade, Bruno
AU - Bouvagnet, Patrice
N1 - Generated from Scopus record by KAUST IRTS on 2023-02-15
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - https://onlinelibrary.wiley.com/doi/10.1002/humu.24132
UR - http://www.scopus.com/inward/record.url?scp=85096526132&partnerID=8YFLogxK
U2 - 10.1002/humu.24132
DO - 10.1002/humu.24132
M3 - Article
SN - 1059-7794
VL - 41
SP - 2167
EP - 2178
JO - Human mutation
JF - Human mutation
IS - 12
ER -