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Identification of novel mutations in the MTM1 gene causing severe and mild forms of X‐linked myotubular myopathy
Author(s) -
BujBello Anna,
Biancalana Valérie,
Moutou Céline,
Laporte Jocelyn,
Mandel JeanLouis
Publication year - 1999
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(199910)14:4<320::aid-humu7>3.0.co;2-o
Subject(s) - hypotonia , missense mutation , biology , congenital myopathy , genetics , muscle weakness , mutation , phenotype , weakness , gene , medicine , muscle biopsy , anatomy , biopsy
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. Hum Mutat 14:320–325, 1999. © 1999 Wiley‐Liss, Inc.