Characterization of mutations in fifty North American patients with X-linked myotubular myopathy.

X-linked myotubular myopathy (MTM1) is a rare developmental disorder of skeletal muscle that is characterized by the presence of abnormal central nuclei in biopsy specimens taken from affected individuals. To date 133 different mutations have been identified in the MTM1 gene worldwide. We report here mutations detected in 50 additional U.S. families with biopsy-proven MTM1. Forty-one of the patients have not been described previously, including 18 with novel mutations. Eighty-eight percent of the mothers of sporadic cases that were studied were identified as carriers, extending the previously reported high-carrier frequency for this disorder. Clinical information collected on the majority of patients helps to further correlate genotype with phenotype, and implications of these data for genetic counseling in families are discussed.