title: Two novel missense mutations in the myostatin gene identified in Japanese patients with Duchenne muscular dystrophy.
abstract: BACKGROUND
  Myostatin is a negative regulator of skeletal muscle growth. Truncating mutations in the myostatin gene have been reported to result in gross muscle hypertrophy. Duchenne muscular dystrophy (DMD), the most common lethal muscle wasting disease, is a result of an absence of muscle dystrophin. Although this disorder causes a rather uniform pattern of muscle wasting, afflicted patients display phenotypic variability. We hypothesized that genetic variation in myostatin is a modifier of the DMD phenotype.
  
  
  METHODS
  We analyzed 102 Japanese DMD patients for mutations in the myostatin gene.
  
  
  RESULTS
  Two polymorphisms that are commonly observed in Western countries, p.55A>T and p.153K>R, were not observed in these Japanese patients. An uncommon polymorphism of p.164E>K was uncovered in four cases; each patient was found to be heterozygous for this polymorphism, which had the highest frequency of the polymorphism observed in the Japanese patients. Remarkably, two patients were found to be heterozygous for one of two novel missense mutations (p.95D>H and p.156L>I). One DMD patient carrying a novel missense mutation of p.95D>H was not phenotypically different from the non-carriers. The other DMD patient was found to carry both a novel mutation (p.156L>I) and a known polymorphism (p.164E>K) in one allele, although his phenotype was not significantly modified. Any nucleotide change creating a target site for micro RNAs was not disclosed in the 3' untranslated region.
  
  
  CONCLUSIONS
  Our results indicate that heterozygous missense mutations including two novel mutations did not produce an apparent increase in muscle strength in Japanese DMD cases, even in a patient carrying two missense mutations.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, 6500017, Japan. 034d595m@y03.kobe-u.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeshima
authors.forename: Kayoko
authors.initials: K
authors.lastname: Saiki
authors.forename: Akiko
authors.initials: A
authors.lastname: Narukage
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Oyazato
authors.forename: Mariko
authors.initials: M
authors.lastname: Yagi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics*; D020125:Mutation, Missense; D055435:Myostatin; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: C525911:MSTN protein, human; D055435:Myostatin; D016212:Transforming Growth Factor beta