Naslov
A biallelic loss-of-function variant in MYZAP is associated with a recessive form of severe dilated cardiomyopathy

Autori
Maver, Aleš ; Žigman, Tamara ; Rangrez, Ashraf Yusuf ; Ćorić, Marijana ; Homolak, Jan ; Šarić, Dalibor ; Skific, Iva ; Udovičić, Mario ; Zekušić, Marija ; Saleem, Umber ; Laufer, Sandra ; Hansen, Arne ; Frey, Norbert ; Barić, Ivo ; Peterlin, Borut

Izvornik
Cold Spring Harbor Molecular Case Studies (2373-2873) 8 (2022), 4; 1-23

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Dilated cardiomyopathy

Sažetak
Abstract 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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA