The Pathophysiological Role of MYBPHL in Dilated Cardiomyopathy

Cardiomyopathy is a leading cause of heart failure and is highly heritable. One common form of cardiomyopathy is dilated cardiomyopathy (DCM), which currently has over 70 identified genes that have been described as causative for the disease. Genetic testing for DCM employs gene panels and has a sensitivity of mutation detection of less than 50%, indicating that additional genes contribution to DCM. Here, we employed whole genome sequencing in a family with DCM and heart block who had previously undergone unrevealing genetic testing. We identified a premature stop codon in the MYBPHL gene, a gene that has not previously been linked to DCM as a likely cause of DCM in this family. Myosin binding protein H (MyBP-H) is a muscle-expressed protein bearing structural similarity to myosin binding protein C (MyBP-C), which is commonly mutated gene in cardiomyopathies.