Analysis of Genomic Testing of Congenital Heart Disease in a Cohort From a Consanguineous Population

Congenital heart disease (CHD) is the most common type of birth defect with tremendous genetic heterogeneity. The aim of our study was to unravel the molecular pathology and the magnitude of recessive genotypes (RGs) in a cohort of CHD from our consanguineous population. In probands with CHD who were consecutively recruited, genetic analysis was conducted based on the most likely etiology to either copy number variants (CNVs) analysis, multigene panel, whole exome sequencing (WES), or whole genome sequencing (WGS). A total of 201 families were recruited, of whom 59.7% were consanguineous. The overall diagnostic yield of genetic testing was 34.8%, with significantly higher yield in syndromic compared to isolated CHD (48.8% vs. 11.8%, respectively, *** p < 0.0001). Pathogenic CNV were identified in 12.4% and single‐nucleotides variants in 22.4%, with biallelic variants in only 6.5% of probands. In negative cases, analysis of WES/WGS data did not reveal plausible variants. The tremendous genetic heterogeneity with a minority of homozygous variants in our cohort suggests that RG may be considered a rare cause of CHD even in consanguineous population. Our findings support the integration of next‐generation sequencing into routine clinical care of CHD and provide relevant ingredients for genetic counseling in consanguineous population.