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

Autor: Dong W; Department of Genetics, Yale School of Medicine, New Haven, Connecticut, USA.; Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, New York, USA., Kaymakcalan H; Department of Pediatrics, Demiroglu Bilim University, Istanbul, Turkey., Jin SC; Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA., Diab NS; Department of Genetics, Yale School of Medicine, New Haven, Connecticut, USA., Tanıdır C; Department of Pediatrics, Mehmet Akif Ersoy Hospital, Istanbul, Turkey., Yalcin ASY; Department of Pediatrics, Demiroglu Bilim University, Istanbul, Turkey., Ercan-Sencicek AG; Department of Genetics, Yale School of Medicine, New Haven, Connecticut, USA.; Biomedical research and translational medicine, Masonic Medical Research Institute, Utica, New York, USA., Mane S; Department of Genetics, Yale School of Medicine, New Haven, Connecticut, USA., Gunel M; Department of Genetics, Yale School of Medicine, New Haven, Connecticut, USA., Lifton RP; Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, New York, USA., Bilguvar K; Department of Genetics, Yale School of Medicine, New Haven, Connecticut, USA.; Department of Genetics, Yale Center for Genomic Analysis, New Haven, Connecticut, USA., Brueckner M; Department of Genetics, Yale School of Medicine, New Haven, Connecticut, USA.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2022 Jun; Vol. 10 (6), pp. e1944. Date of Electronic Publication: 2022 Apr 28.
DOI: 10.1002/mgg3.1944
Abstrakt: 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.
Methods: We recruited 73 CHD probands from consanguineous families in Turkey and used whole-exome sequencing (WES) to identify genetic lesions in these patients.
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.
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.
(© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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