MITOCHONDRIAL ALTERATIONS IN DYNAMIN 2-RELATED CENTRONUCLEAR MYOPATHY

Centronuclear myopathy (CNM) is clinically characterized by diffuse involvement of skeletal muscles, with onset mainly in early childhood and a slowly progressive course. The basic histological abnormalities in muscle biopsies are a high percentage of centrally located nuclei of muscle fibers, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers(1-3). Three forms of the disease have been recognized that differ in age of onset and severity of the symptoms: The severe X-linked myotubular myopathy, caused by mutations in the MTM1 gene; the childhood onset form; and the juvenile/adult onset form that fully manifests during the third decade of life. in the juvenile/adult onset form, most of the families have an autosomal dominant inheritance, and patients present with a slowly progressive disease, but with mild clinical manifestations'. This form has been associated with mutations in the dynamin 2 gene (DNM2)(4). More recently, N icot et al.(5) described in three CNM families with autosomal recessive inheritance mutations in amphiphysin 2 gene, which disrupt the interaction with dynamin 2 protein.