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

Cytogenetic Analysis Family Female Fetus / abnormalities Heart Defects, Congenital / genetics Heterotaxy Syndrome / genetics Heterozygote High-Throughput Nucleotide Sequencing Homozygote Humans Male Mutation / genetics Pedigree

congenital heart defects consanguinity fetus heterotaxy midline anomaly next-generation sequencing

Journal

Human mutation

ISSN: 1098-1004

Titre abrégé: Hum Mutat

Pays: United States

ID NLM: 9215429

Informations de publication

Date de publication:
12 2020

Historique:

received: 14 02 2020

revised: 21 09 2020

accepted: 02 10 2020

pubmed: 2 11 2020

medline: 26 11 2021

entrez: 1 11 2020

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1002/humu.24132 PMID: 33131162

pubmed: 33131162

doi: 10.1002/humu.24132

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

2167-2178

Informations de copyright

Références

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