P3246Systematic analysis of cardiac disease genes in pediatric cardiomyopathy patients identifies novel genetic variants

Cardiomyopathy in pediatric patients is a serious, life-threatening condition that may result from genetic defects. While the mechanisms leading to cardiomyopathy in adults are well-established, the underlying genetic mechanisms, early pathological events and other disease promoting factors are poorly characterized in children. To analyze the genetic defects causing pediatric heart failure we investigated a cohort of 82 patients (<18 years) with hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), left ventricular noncompaction cardiomyopathy (LVNC), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM). Screening of index patients and their first degree relatives was performed with next generation sequencing (NGS) for genetic variants in 174 target genes (Illumina TruSight Cardio Sequencing Panel). The identified genetic variants were bioinformatically filtered with a minor allele frequency (MAF) of <0.001, evaluated with in silico pathogenicity prediction tools and validated on the ExAC reference data base. Case-specific interpretation of the variants occurred in the familial and functional protein context according to the American College of Medical Genetics and Genomics (ACMG) guidelines.