Phenotypic Variability in iPSC-Induced Cardiomyocytes and Cardiac Fibroblasts Carrying Diverse LMNA Mutations.

ABSTRACT: Mutations in the LMNA gene (encoding lamin A/C) are a significant cause of familial arrhythmogenic cardiomyopathy. Although the penetrance is high, there is considerable phenotypic variability in disease onset, rate of progression, arrhythmias, and severity of myopathy. To begin to address whether this variability stems from specific LMNA mutation sites and types, we generated seven patient-specific induced pluripotent stem cell (iPSC) lines with various LMNA mutations. IPSC-derived cardiomyocytes (iCMs) and cardiac fibroblasts (iCFs) were differentiated from each line for phenotypic analyses. LMNA expression and extracellular signal-regulated kinase pathway activation were perturbed to differing degrees in both iCMs and iCFs from the different lines. Enhanced a

SUBMITTER: Yang J 

PROVIDER: S-EPMC8716763 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature