Regulatory Light Chain (MYL2) Mutations in Familial Hypertrophic Cardiomyopathy

The knowledge about the role and phenotypic expression of the regulatory light chain gene (MYL2) in hypertrophic cardiomyopathy (HCM) is still poor and needs further study. To date there are only 5 papers where its phenotypic expression is mentioned and it has been suggested that it is related to midventricular obstruction. We looked for MYL2 variants in 124 consecutive HCM index patients. Besides, we collected and reviewed all the information and clinical data from the literature and from our cohort on MYL2 mutations and performed a systematic assessment of their pathogenicity and phenotypic expression. In our cohort two novel MYL2 mutations were found (2,4%): p.Asp166Ala, pathogenic and related to obstructive septal asymmetrical hypertrophy and with a good prognosis, and p.Ile158Leu, likely pathogenic and probably related to a good prognosis. Moreover, 13 mutations in MYL2 have been published to date, where septal asymmetrical hypertrophy and a good prognosis were the most common clinical findings, although relevant phenotypic information was not always provided. Prevalence of MYL2 mutations is 2,4% in our cohort. MYL2 mutations are frequently related to a good prognosis and to septal asymmetrical hypertrophy. Relevant clinical information is seldom described across the literature and further effort on this matter should be taken.