Key result
Homozygous premature termination variant in MYZAP linked to severe recessive DCM.
Why the study?
About 50% of DCM cases can be attributed to monogenic causes, whereas the aetiology in the remaining patients remains unexplained.
Case Report (n=2)
Biallelic loss-of-function variants in the MYZAP gene are associated with a recessive form of severe dilated cardiomyopathy, causing severe contractile dysfunction.
Supports MYZAP screening in recessive familial dilated cardiomyopathy; leaves open prevalence and validation in larger cohorts.
PURPOSE: Dilated cardiomyopathy (DCM) is a primary disorder of the cardiac muscle, characterised by dilatation of the left ventricle and contractile dysfunction. About 50% of DCM cases can be attributed to monogenic causes, whereas the aetiology in the remaining patients remains unexplained. METHODS: We report a family with two brothers affected by severe DCM with onset in the adolescent period. Using exome sequencing, we identified a homozygous premature termination variant in the MYZAP gene in both affected sibs. MYZAP encodes for myocardial zonula adherens protein - a conserved cardiac protein in the intercalated disc structure of cardiomyocytes. RESULTS: The effect of the variant was demonstrated by light and electron microscopy of the heart muscle and immunohistochemical and Western blot analysis of MYZAP protein in the heart tissue of the proband. Functional characterization using patient-derived induced pluripotent stem cell cardiomyocytes revealed significantly lower force and longer time to peak contraction and relaxation consistent with severe contractile dysfunction. CONCLUSION: We provide independent support for the role of biallelic loss-of-function MYZAP variants in dilated cardiomyopathy. This report extends the spectrum of cardiac disease associated with dysfunction of cardiac intercalated disc junction and sheds light on the mechanisms leading to DCM.
No takes yet. Share an insight, caveat, or question.
Maver et al. (2022) conducted a case report in Dilated cardiomyopathy (n=2). Exome sequencing and functional analysis was evaluated on Identification of the genetic etiology of familial dilated cardiomyopathy. A homozygous premature termination variant in the MYZAP gene (c.236C>A, p.Ser79Ter) was identified as the cause of a recessive form of severe dilated cardiomyopathy in two affected brothers.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: