title: Characterization of MTM1 mutations in 31 Japanese families with myotubular myopathy, including a patient carrying 240 kb deletion in Xq28 without male hypogenitalism.
abstract: X-linked myotubular myopathy is a congenital muscle disorder due to MTM1 mutation, and is characterized clinically by generalized muscle weakness and hypotonia at birth usually resulting in early death. We newly identified 26 unrelated Japanese patients with MTM1 mutations by genomic DNA and transcript analysis, including 12 novel mutations. Among 31 patients, including our previously reported five patients, the c.1261-10A>G splice site mutation was the most frequent mutation. Three mutations, one missense and two splice site, were associated with milder phenotype. Of particular interest, one boy had a 240 kb deletion in Xq28 encompassing CXorf6 (formerly F18), MTM1 and MTMR1 but was not accompanied by hypogenitalism. CXorf6, which have been implicated in male sexual development, was not entirely deleted in this boy, resulting in the fusion with the MTMR1 gene. A chimeric fusion transcript was detected in patient's muscle by RT-PCR, suggesting this fusion gene product avoids the phenotype. This deletion led us to refine the critical region of CXorf6 for the development of male genitalia.
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Tzung-Chang
authors.initials: TC
authors.lastname: Tsai
authors.forename: Hideo
authors.initials: H
authors.lastname: Horinouchi
authors.forename: Satoru
authors.initials: S
authors.lastname: Noguchi
authors.forename: Narihiro
authors.initials: N
authors.lastname: Minami
authors.forename: Kumiko
authors.initials: K
authors.lastname: Murayama
authors.forename: Yukiko K
authors.initials: YK
authors.lastname: Hayashi
authors.forename: Ikuya
authors.initials: I
authors.lastname: Nonaka
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D004252:DNA Mutational Analysis; D004274:DNA, Recombinant; D005192:Family Health; D043326:Glucan 1,3-beta-Glucosidase; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000473:pathology; D020125:Mutation, Missense; D020914:Myopathies, Structural, Congenital / Q000235:genetics*; D010641:Phenotype; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017384:Sequence Deletion / Q000235:genetics*; D012729:Sex Chromosome Aberrations
chemical_list: D004274:DNA, Recombinant; D012333:RNA, Messenger; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin; D043326:Glucan 1,3-beta-Glucosidase