title: A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast.
abstract: X-linked recessive myotubular myopathy (MTM1) is characterized by severe hypotonia and generalized muscle weakness, with impaired maturation of muscle fibres. We have restricted the candidate region to 280 kb and characterized two candidate genes using positional cloning strategies. The presence of frameshift or missense mutations (of which two are new mutations) in seven patients proved that one of these genes is indeed implicated in MTM1. The protein encoded by the MTM1 gene is highly conserved in yeast, which is surprising for a muscle specific disease. The protein contains the consensus sequence for the active site of tyrosine phosphatases, a wide class of proteins involved in signal transduction. At least three other genes, one located within 100 kb distal from the MTM1 gene, encode proteins with very high sequence similarities and define, together with the MTM1 gene, a new family of putative tyrosine phosphatases in man.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/U LP, B.P. 163, C.U. de Strasbourg, France.
authors.forename: J
authors.initials: J
authors.lastname: Laporte
authors.forename: L J
authors.initials: LJ
authors.lastname: Hu
authors.forename: C
authors.initials: C
authors.lastname: Kretz
authors.forename: J L
authors.initials: JL
authors.lastname: Mandel
authors.forename: P
authors.initials: P
authors.lastname: Kioschis
authors.forename: J F
authors.initials: JF
authors.lastname: Coy
authors.forename: S M
authors.initials: SM
authors.lastname: Klauck
authors.forename: A
authors.initials: A
authors.lastname: Poustka
authors.forename: N
authors.initials: N
authors.lastname: Dahl
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence; D005800:Genes, Fungal; D008040:Genetic Linkage; D006801:Humans; D008969:Molecular Sequence Data; D009123:Muscle Hypotonia / Q000235:genetics; D009135:Muscular Diseases / Q000235:genetics*; D009154:Mutation; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014018:Tissue Distribution; D014960:X Chromosome
chemical_list: D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin