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

ABSTRACT 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.

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Journal
Clinical Genetics
Published
2026-10-08
DOI
https://doi.org/10.1111/cge.70250
Primary Topic
Genomics and Rare Diseases
Type
article
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article

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

Hadeel Binomar, Sahar Tulbah, Dimpna Calila Albert, Ali A. Alakhfash et al.
Clinical Genetics
Genomics and Rare Diseases
article

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

Hadeel Binomar, Sahar Tulbah, Dimpna Calila Albert, Ali A. Alakhfash, Abdulrahman A Almesned, Abdullah Alwadai, Zarghuna M.A. Shinwari, Mohammed Alhabdan, Maarab Alkorashy, Abdullah Alqwaee, Waleed Al-Manea, Ghassan Siblini, Alanood I. Alqahtani, Abdullah Al-Sehly, Zuhair Nasser Al-Hassnan, Abdulaziz Fadel Alfadley, Mansour Aljoufan, Hamzah Naji, Amani Othman, Saud Takroni, Abdullah Alhuzaimi, Zohair Alhalees, Faten AlHadheq, Abeer Almostafa, Amal AlDowaihi, Nadiah Al‐Ruwaili, Saud Aloufi, Fadel Alfadley
article en

Abstract

ABSTRACT 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.

Clinical Genetics
Alfaisal University (SA), Prince Sultan University (SA), King Faisal Specialist Hospital & Research Centre (SA), King Fahd Hospital of the University (SA), King Fahad Specialist Hospital (SA), Saud Al-babtain Cardiac Centre (SA)
Openalex Percentile: Top 14%
Genomics and Rare Diseases
DOISourceOpenAlex
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