The contribution of mutations in MYH7 to the onset of cardiomyopathy

In this issue of the Netherlands Heart Journal, van der Linde et al. describe a novel Dutch founder mutation (MYH7p.Asn1918Lys) in MYH7, the gene encoding myosin heavy chain 7, leading to cardiomyopathy and congenital heart defects [1]. Van der Linde et al. showed that the MYH7p.Asn1918Lys mutation resulted in predominantly dilated cardiomyopathy (DCM) but was also present in patients suffering from peripartum cardiomyopathy (PPCM), non-compaction cardiomyopathy (NCCM) and congenital heart defects [1]. Mutations in many different genes have been implicated to be causal to DCM [2]. However, the same genes are often also implicated in the onset of other cardiomyopathies such as hypertrophic cardiomyopathy (HCM), NCCM or restrictive cardiomyopathy [2]. It is therefore difficult to understand how these mutations contribute to the onset of disease and why one gene mutation causes diverse cardiomyopathy phenotypes. This is especially the case for mutations in MYH7 which has been suggested to be an important gene in HCM as well as DCM pathogenesis. Gene variants can be benign and it is often difficult to establish which variants are pathogenic. The Exome Aggregation Consortium (ExAC) has recently re-assessed various mutations assumed to be causal to the onset of cardiomyopathy [3]. According to the ExAC, many variants previously assumed to be causal in DCM such as mutations in MYH6, SCN5A and MYBPC3 were not found in excess in the DCM population compared with ~60,000 controls, making it unlikely that they played a role in the