Mutation spectrum of congenital heart disease in a consanguineous Turkish population. Issue 6 (28th April 2022)

• Record Type: Journal Article
• Authors: Dong, Weilai; Kaymakcalan, Hande; Jin, Sheng Chih; Diab, Nicholas S.; Tanıdır, Cansaran; Yalcin, Ali Seyfi Yalim; Ercan‐Sencicek, A. Gulhan; Mane, Shrikant; Gunel, Murat; Lifton, Richard P.; Bilguvar, Kaya; Brueckner, Martina
• Is Part Of: Molecular genetics & genomic medicine. Volume 10:Issue 6(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-04-28
• Subjects: congenital heart disease -- consanguinity -- genetics -- mutation; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.1944
• Languages: English
• ISSNs: 2324-9269

Abstract

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. 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. Abstract : WES screen of 73 CHD probands from consanguineous unions in Turkey revealed that 13.7% of cases can be explained by genomic alterations, especially homozygous variants. Our study thus provided valuable information about the genetic landscape of CHD in consanguineous families in Turkey.