Clinical Exome Sequencing Revealed a De Novo FLNC Mutation in a Child with Restrictive Cardiomyopathy

Restrictive cardiomyopathy (RCM) is a rare disease of the myocardium caused by mutations in several genes including TNNT2, DES, TNNI3, MYPN and FLNC. Individuals affected by RCM often develop heart failure at a young age, requiring early heart transplantation. A 7-year-old patient was referred for genetic testing following a diagnosis of restrictive cardiomyopathy. Clinical exome sequencing analysis identified a likely pathogenic mutation in the FLNC gene [(NM_001458.5 c.6527_6547dup p.(Arg2176_2182dup)]. Its clinical relevance was augmented by the fact that this variant was absent in the parents and was thus interpreted as de novo. Genetic testing is a powerful tool to clarify the diagnosis, guide intervention strategies and enable cascade testing in patients with pediatric-onset RCM.