Congenital neuromuscular disease with uniform type 1 fiber and RYR1 mutation

Academic Article

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. CONCLUSION: 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. ©2008AAN Enterprises, Inc.
  • Authors

    Published In

  • Neurology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Sato I; Wu S; Ibarra MCA; Hayashi YK; Fujita H; Tojo M; Oh SJ; Nonaka I; Noguchi S; Nishino I
  • Start Page

  • 114
  • End Page

  • 122
  • Volume

  • 70
  • Issue

  • 2