Gene expression profiling of fibroblasts in a family with LMNA-related cardiomyopathy reveals molecular pathways implicated in disease pathogenesis.

IGFBP5 may contribute in maintaining signaling pathway homeostasis, which may lead to the absence of notable molecular and structural abnormalities in unaffected tissues such as fibroblasts. Compensatory mechanisms from other nuclear membrane proteins were not found. Our results also demonstrate that only one copy of the wild type allele is sufficient for normal levels of Lamin A/C protein to maintain physiological function in an unaffected cell type. This suggests that affected cell types such as cardiac tissues may be more sensitive to haploinsufficiency of Lamin A/C. These results provide insight into the molecular mechanism of disease with a possible explanation for the tissue specificity of LMNA-related dilated cardiomyopathy.