We are now offering testing for the 3 known genes for Centronuclear/Myotubular Myopathy, MTM1, DNM2, and BIN1.
- X-linked Myotubular Myopathy is caused by mutations in the MTM1 gene, which codes for the myotubular protein, a highly conserved phosphatase thought to be involved in cellular transport and trafficking. Approximately 80% of males with a diagnosis of myotubular myopathy by muscle biopsy will have a mutation in MTM1 identifiable by sequence analysis. About 7% of mutations in MTM1 are deletions.
- DNM2 is the only gene currently known to be associated with autosomal dominant CNM. DNM2 mutations account for most, but not all, cases of CNM with autosomal dominant inheritance or later onset. To date, fewer than 10 disease-associated mutations have been identified in the DNM2 gene. Mutations in the PH domain of the protein are more likely to be associated with severe neonatal onset, whereas the milder phenotypes with later onset are often caused by mutations in the middle domain.
- BIN1 is the only gene currently known to be associated with autosomal recessive CNM. BIN1 mutations appear to be relatively rare, accounting for approximately 25% of cases of CNM with apparent recessive inheritance but only a small percentage of all CNM cases combined. To date, only a small number of mutations have been described in the BIN1 gene, including several missense changes and one nonsense mutation.