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Mutation spectrum of congenital heart disease in a consanguineous Turkish population.

Authors :
Dong W
Kaymakcalan H
Jin SC
Diab NS
Tanıdır C
Yalcin ASY
Ercan-Sencicek AG
Mane S
Gunel M
Lifton RP
Bilguvar K
Brueckner M
Source :
Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2022 Jun; Vol. 10 (6), pp. e1944. Date of Electronic Publication: 2022 Apr 28.
Publication Year :
2022

Abstract

Backgrounds: While many studies agree that consanguinity increases the rate of congenital heart disease (CHD), few genome analyses have been conducted with consanguineous CHD cohorts.<br />Methods: We recruited 73 CHD probands from consanguineous families in Turkey and used whole-exome sequencing (WES) to identify genetic lesions in these patients.<br />Results: On average, each patient had 6.95 rare damaging homozygous variants, 0.68 of which are loss-of-function (LoF) variants. Seven patients (9.6%) carried damaging homozygous variants in five causal CHD genes. Six of those patients exhibited laterality defects (six HTX and one D-TGA). Three additional patients (4.1%) harbored other types of CHD-associated genomic alterations, which overall explained 13.7% (10/73) of the cohort. The contribution from recessive variants in our cohort is higher than 1.8% reported from a cohort of 2871 CHD subjects where 5.6% of subjects met the criteria for consanguinity.<br />Conclusions: Our WES screen of a Turkish consanguineous population with structural CHD revealed its unique genetic architecture. Six of seven damaging homozygous variants in CHD causal genes occur in the setting of laterality defects implies a strong contribution from consanguinity to these defects specifically. Our study thus provided valuable information about the genetic landscape of CHD in consanguineous families in Turkey.<br /> (© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Details

Language :
English
ISSN :
2324-9269
Volume :
10
Issue :
6
Database :
MEDLINE
Journal :
Molecular genetics & genomic medicine
Publication Type :
Academic Journal
Accession number :
35481623
Full Text :
https://doi.org/10.1002/mgg3.1944