AUTHOR=Perepelina Kseniya , Zaytseva Anastasia , Khudiakov Aleksandr , Neganova Irina , Vasichkina Elena , Malashicheva Anna , Kostareva Anna 

TITLE=LMNA mutation leads to cardiac sodium channel dysfunction in the Emery-Dreifuss muscular dystrophy patient

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.932956

DOI=10.3389/fcvm.2022.932956

ISSN=2297-055X

ABSTRACT=<p>Pathogenic variants in the <italic>LMNA</italic> gene are known to cause laminopathies, a broad range of disorders with different clinical phenotypes. <italic>LMNA</italic> genetic variants lead to tissue-specific pathologies affecting various tissues and organs. Common manifestations of laminopathies include cardiovascular system abnormalities, in particular, cardiomyopathies and conduction disorders. In the present study, we used induced pluripotent stem cells from a patient carrying <italic>LMNA</italic> p.R249Q genetic variant to create an <italic>in vitro</italic> cardiac model of laminopathy. Induced pluripotent stem cell-derived cardiomyocytes with <italic>LMNA</italic> p.R249Q genetic variant showed a decreased sodium current density and an impaired sodium current kinetics alongside with changes in transcription levels of cardiac-specific genes. Thus, we obtained compelling <italic>in vitro</italic> evidence of an association between <italic>LMNA</italic> p.R249Q genetic variant and cardiac-related abnormalities.</p>