title: Congenital neuromuscular disease with uniform type 1 fiber and RYR1 mutation.
abstract: BACKGROUND
  Congenital neuromuscular disease with uniform type 1 fiber (CNMDU1) is a rare form of congenital myopathy, which is pathologically diagnosed by the presence of more than 99% of type 1 fiber, with no specific structural changes. Its pathogenic mechanism is still unknown. We recently reported that almost all patients with central core disease (CCD) with ryanodine receptor 1 gene (RYR1) mutations in the C-terminal domain had type 1 fibers, nearly exclusively, in addition to typical central cores.
  
  
  OBJECTIVE
  To investigate whether CNMDU1 is associated with RYR1 mutation.
  
  
  METHODS
  We studied 10 unrelated Japanese patients who were diagnosed to have CNMDU1 based on clinical features and muscle pathology showing more than 99% type 1 muscle fibers. We extracted genomic DNA from frozen muscles and directly sequenced all 106 exons and their flanking intron-exon boundaries of RYR1.
  
  
  RESULTS
  Four of 10 patients had a heterozygous mutation, three missense and one deletion, all in the C-terminal domain of RYR1. Two missense mutations were previously reported in CCD patients. Clinically, patients with mutations in RYR1 showed milder phenotype compared with those without mutations.
  
  
  CONCLUSIONS
  Congenital neuromuscular disease with uniform type 1 fiber (CNMDU1) in 40% of patients is associated with mutations in the C-terminal domain of RYR1, suggesting that CNMDU1 is allelic to central core disease at least in some patients.
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: I
authors.initials: I
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Wu
authors.forename: M C A
authors.initials: MC
authors.lastname: Ibarra
authors.forename: Y K
authors.initials: YK
authors.lastname: Hayashi
authors.forename: H
authors.initials: H
authors.lastname: Fujita
authors.forename: M
authors.initials: M
authors.lastname: Tojo
authors.forename: S J
authors.initials: SJ
authors.lastname: Oh
authors.forename: I
authors.initials: I
authors.lastname: Nonaka
authors.forename: S
authors.initials: S
authors.lastname: Noguchi
authors.forename: I
authors.initials: I
authors.lastname: Nishino
mesh_terms: D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D020914:Myopathies, Structural, Congenital / Q000235:genetics* / Q000473:pathology; D012189:Retrospective Studies; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel