X-linked myotubular myopathy (XLMTM) is a congenital muscular disease 
characterized by severe hypotonia and generalized muscle weakness, leading in 
most cases to early postnatal death. The gene responsible for the disease, MTM1, 
encodes a dual specificity phosphatase, named myotubularin, which is highly 
conserved throughout evolution. To date, 139 MTM1 mutations in independent 
patients have been reported, corresponding to 93 different mutations. In this 
report we describe the identification of 21 mutations (14 novel) in XLMTM 
patients. Seventeen mutations are associated with a severe phenotype in males, 
with death occurring mainly before the first year of life. However, four 
mutations-three missense (R241C, I225T, and novel mutation P179S) and one 
single-amino acid deletion (G294del)-were found in patients with a much milder 
phenotype. These patients, while having a severe hypotonia at birth, are still 
alive at the age of 4, 7, 13, and 15 years, respectively, and display mild to 
moderate muscle weakness.