title: Identification of novel mutations in the MTM1 gene causing severe and mild forms of X-linked myotubular myopathy.
abstract: 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.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch Cedex, France.
authors.forename: A
authors.initials: A
authors.lastname: Buj-Bello
authors.forename: V
authors.initials: V
authors.lastname: Biancalana
authors.forename: C
authors.initials: C
authors.lastname: Moutou
authors.forename: J
authors.initials: J
authors.lastname: Laporte
authors.forename: J L
authors.initials: JL
authors.lastname: Mandel
mesh_terms: D000293:Adolescent; D002648:Child; D002874:Chromosome Mapping; D004247:DNA / Q000097:blood / Q000302:isolation & purification; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D014644:Genetic Variation; D018392:Genomic Imprinting; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D020914:Myopathies, Structural, Congenital / Q000235:genetics* / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D017384:Sequence Deletion; D014960:X Chromosome
chemical_list: D004247:DNA; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin