Effect of the Mutated p.H222P A-type Lamins on Gene Expression in Both Patient-Derived Cardiomyocytes and Mouse Models of Dilated Cardiomyopathy

Mutation on A-type lamins encoding gene can lead to a wide-range of diseases called laminopathies, including dilated cardiomyopathy. Nuclear lamins are integral to a physical continuum connecting the extracellular environment and the nuclear interior, playing a crucial role in load-bearing tissues like the heart to preserve mechanical integrity and genome stability. To investigate the impact of the LMNA p.H222P mutation on gene expression, we conducteed bulk RNA-seq in hiPSCs-derived cardiomyocytes and mouse cardiomyocytes, both carrying this mutation. Our results reveal that the LMNA p.H222P mutation leads to dysregulated gene expression, which may contribute to LMNA cardiomyopathy pathogenesis.