title: Mutations in the MTM1 gene implicated in X-linked myotubular myopathy. ENMC International Consortium on Myotubular Myopathy. European Neuro-Muscular Center.
abstract: X-linked recessive myotubular myopathy (XLMTM) is characterized by severe hypotonia and generalized muscle weakness, with impaired maturation of muscle fibres. The gene responsible, MTM1, was identified recently by positional cloning, and encodes a protein (myotubularin) with a tyrosine phosphatase domain (PTP). Myotubularin is highly conserved through evolution and defines a new family of putative tyrosine phosphatases in man. We report the identification of MTM1 mutations in 55 of 85 independent patients screened by single-strand conformation polymorphism for all the coding sequence. Large deletions were observed in only three patients. Five point mutations were found in multiple unrelated patients, accounting for 27% of the observed mutations. The possibility of detecting mutations and determining carrier status in a disease with a high proportion of sporadic cases is of importance for genetic counselling. More than half of XLMTM mutations are expected to inactivate the putative enzymatic activity of myotubularin, either by truncation or by missense mutations affecting the predicted PTP domain. Additional mutations are missenses clustered in two regions of the protein. Most of these affect amino acids conserved in the homologous yeast and Caenorhabditis elegans proteins, thus indicating the presence of other functional domains.
authors.affiliation: IGBMC, CNRS/INSERM/ULP, Illkirch, France.
authors.forename: J
authors.initials: J
authors.lastname: Laporte
authors.forename: C
authors.initials: C
authors.lastname: Guiraud-Chaumeil
authors.forename: M C
authors.initials: MC
authors.lastname: Vincent
authors.forename: J L
authors.initials: JL
authors.lastname: Mandel
authors.forename: S M
authors.initials: SM
authors.lastname: Tanner
authors.forename: S
authors.initials: S
authors.lastname: Liechti-Gallati
authors.forename: C
authors.initials: C
authors.lastname: Wallgren-Pettersson
authors.forename: N
authors.initials: N
authors.lastname: Dahl
authors.forename: W
authors.initials: W
authors.lastname: Kress
authors.forename: P A
authors.initials: PA
authors.lastname: Bolhuis
authors.forename: M
authors.initials: M
authors.lastname: Fardeau
authors.forename: F
authors.initials: F
authors.lastname: Samson
authors.forename: E
authors.initials: E
authors.lastname: Bertini
mesh_terms: D017398:Alternative Splicing; D005091:Exons / Q000235:genetics; D016368:Frameshift Mutation; D017353:Gene Deletion; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D007231:Infant, Newborn; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009123:Muscle Hypotonia / Q000235:genetics*; D018908:Muscle Weakness / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D017422:Sequence Analysis, DNA; D014960:X Chromosome
chemical_list: D005819:Genetic Markers; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin