Dilated Cardiomyopathy in a Kurdish–Arab Cohort Using Targeted Next-Generation Sequencing
TL;DR
A high diagnostic yield of DCM was found, particularly in consanguineous families, including an SCN5A recurrent variant, which highlights the utility of targeted NGS in a consanguineous population.
Abstract
Background: Pediatric dilated cardiomyopathy (DCM) is a genetically heterogeneous disorder with limited population-specific genetic data in Middle Eastern cohorts. Methods: Twenty-three pediatric DCM patients from a predominantly Kurdish–Arab consanguineous population underwent comprehensive clinical evaluation and targeted next-generation sequencing (NGS) using a 152-gene cardiomyopathy panel. Variants were classified according to ACMG/AMP guidelines. Results: Targeted NGS identified 163 rare variants; 24 (14.7%) were pathogenic/likely pathogenic (P/LP), 76 (46.6%) were variants of uncertain significance (VUS), and 63 (38.7%) were benign/likely benign. The overall diagnostic yield was 78.3% (18/23). The SCN5A c.1921delC (p.Gln641ArgfsTer3) frameshift variant was the most frequently detected P/LP variant, present in 69.6% of patients. No significant genotype–phenotype correlations were observed for SCN5A c.1921delC regarding age of onset, left ventricular ejection fraction, or valvular/structural abnormalities. Parental consanguinity was high (66.7%), and disease onset occurred early (mean 2.0 ± 3.27 years). Conclusions: This is the first genetic evaluation of a pediatric cohort with DCM from a mixed Kurdish–Arab population. A high diagnostic yield of DCM was found, particularly in consanguineous families, including an SCN5A recurrent variant. The study highlights the utility of targeted NGS in a consanguineous population. Further related studies are required in this region.