Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy

Emery-Dreifuss muscular dystrophy (EMD) is a condition characterized by the clinical triad of early-onset contractures, progressive weakness in humero peroneal muscles, and cardiomyopathy with conduction block. The disease was described for the first time as an X-linked muscular dystrophy, but autoso mal dominant and autosomal recessive forms were reported. The genes for X-l inked EMD and autosomal dominant EMD (AD-EMD) were identified. We report he re that heterozygote mutations in LMNA, the gene for AD-EMD, may cause dive rse phenotypes ranging from typical EMD to no phenotypic effect. Our result s show that LMNA mutations are also responsible for the recessive form of t he disease. Our results give further support to the notion that different g enetic forms of EMD have a common pathophysiological background. The distri bution of the mutations in AD-EMD patients (in the tail and in the 2A rod d omain) suggests that unique interactions between lamin A/C and other nuclea r components exist that have an important role in cardiac and skeletal musc le function.