Lamin A + C R453W Products

The lamin A gene is important in making nuclear structure and substructures for DNA replication appropriately in cells. The R453W mutation of LMNA, however, negates much of these normal characteristics, and instead causes the phenotypes of Emery-Dreifuss muscular dystrophy (EDMD). The mutation impairs myoblast formation and differentiation, and contributes to muscle wasting. R453W lamin changes the location of the H2K27me3 modified histone interaction with chromatin, which inactivates certain downstream genes. It also affects the normal lamin function of scaffolding substrates for the MEK-ERK pathway, and disrupts the structure of other binding sites. Thus, R453W seems to cause phenotypes of muscular dystrophy both through direct genetic impact, but also through epigenetic influence over normal scaffolding functionality related to DNA replication.