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MTM1 mutations in X‐linked myotubular myopathy
Author(s) -
Laporte Jocelyn,
Biancalana Valérie,
Tanner Stephan M.,
Kress Wolfram,
Schneider Vreni,
WallgrenPettersson Carina,
Herger Franziska,
BujBello Anna,
Blondeau François,
LiechtiGallati Sabina,
Mandel JeanLouis
Publication year - 2000
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(200005)15:5<393::aid-humu1>3.0.co;2-r
Subject(s) - missense mutation , biology , genetics , point mutation , gene , mutation , phenotype , congenital myopathy , medicine , biopsy , muscle biopsy
X‐linked myotubular myopathy (XLMTM; MIM# 310400) is a severe congenital muscle disorder caused by mutations in the MTM1 gene. This gene encodes a dual‐specificity phosphatase named myotubularin, defining a large gene family highly conserved through evolution (which includes the putative anti‐phosphatase Sbf1/hMTMR5). We report 29 mutations in novel cases, including 16 mutations not described before. To date, 198 mutations have been identified in unrelated families, accounting for 133 different disease‐associated mutations which are widespread throughout the gene. Most point mutations are truncating, but 26% (35/133) are missense mutations affecting residues conserved in the Drosophila ortholog and in the homologous MTMR1 gene. Three recurrent mutations affect 17% of the patients, and a total of 21 different mutations were found in several independent families. The frequency of female carriers appears higher than expected (only 17% are de novo mutations). While most truncating mutations cause the severe and early lethal phenotype, some missense mutations are associated with milder forms and prolonged survival (up to 54 years). Hum Mutat 15:393–409, 2000. © 2000 Wiley‐Liss, Inc.