Exome sequencing identifies KIAA1377 and C5orf42 as susceptibility genes for monomelic amyotrophy

Neuromuscul Disord. 2012 May;22(5):394-400. doi: 10.1016/j.nmd.2011.11.006. Epub 2012 Jan 20.


Precise topographic localization, predominance in males mostly of Asian origin, and existence of some familial cases suggest a genetic background for monomelic amyotrophy. To identify susceptibility genes for monomelic amyotrophy, we performed whole-exome sequencing of four unrelated patients with monomelic amyotrophy and detected a total of 45 novel nonsynonymous single-nucleotide polymorphisms as unique variants to monomelic amyotrophy compared to control exomes. Genetic association analysis showed significant association with monomelic amyotrophy in the Gly668Ser variant of the KIAA1377 gene (odds ratio=4.62, P-value=0.0040) and the Pro1794Leu variant of the C5orf42 gene (odds ratio=4.63, P-value=0.0040). Moreover, the combination of two variants increased the risk of monomelic amyotrophy (P=1.4×10(-5), OR=61.69, 95% confidence interval=9.62-394.94, in case of combination of two heterozygotes). These data suggest that KIAA1377 and C5orf42 synergistically play a role as susceptibility genes for monomelic amyotrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Asian People / genetics
  • Cell Cycle Proteins
  • DNA Mutational Analysis
  • Exome / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Spinal Muscular Atrophies of Childhood / diagnosis
  • Spinal Muscular Atrophies of Childhood / genetics*
  • Young Adult


  • CEP126 protein, human
  • CPLANE1 protein, human
  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins

Supplementary concepts

  • Amyotrophy, monomelic