Journal of Neurology

, Volume 259, Issue 9, pp 1913–1922

Clinical, pathological, and genetic mutation analysis of sporadic inclusion body myositis in Japanese people

  • Huaying Cai
  • Ichiro Yabe
  • Kazunori Sato
  • Takahiro Kano
  • Masakazu Nakamura
  • Hideki Hozen
  • Hidenao Sasaki
Original Communication

DOI: 10.1007/s00415-012-6439-0

Cite this article as:
Cai, H., Yabe, I., Sato, K. et al. J Neurol (2012) 259: 1913. doi:10.1007/s00415-012-6439-0

Abstract

Previous studies have identified several genetic loci associated with the development of familial inclusion body myopathy. However, there have been few genetic analyses of sporadic inclusion body myositis (sIBM). In order to explore the molecular basis of sIBM and to investigate genotype-phenotype correlations, we performed a clinicopathological analysis of 21 sIBM patients and screened for mutations in the Desmin, GNE, MYHC2A, VCP, and ZASP genes. All coding exons of the five genes were sequenced directly. Definite IBM was confirmed in 14 cases, probable IBM in three cases, and possible IBM in four cases. No cases showed missense mutations in the Desmin, GNE, or VCP genes. Three patients carried the missense mutation c.2542T>C (p.V805A) in the MYHC2A gene; immunohistochemical staining for MYHC isoforms in these three cases showed atrophy or loss of muscle fibers expressing MYHC IIa or IIx. One patient harbored the missense mutation c.1719G>A (p.V566M) in the ZASP gene; immunohistochemical studies of Z-band-associated proteins revealed Z-band abnormalities. Both of the novel heterogeneous mutations were located in highly evolutionarily conserved domains of their respective genes. Cumulatively, these findings have expanded our understanding of the molecular background of sIBM. However, we advocate further clinicopathology and investigation of additional candidate genes in a larger cohort.

Keywords

Inclusion body myositisDesminUDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE)Myosin heavy chain IIa (MYHC2A)Valosin-containing protein (VCP)Z-band alternatively spliced PDZ-motif containing protein (ZASP)

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Huaying Cai
    • 1
  • Ichiro Yabe
    • 1
  • Kazunori Sato
    • 1
  • Takahiro Kano
    • 1
  • Masakazu Nakamura
    • 1
  • Hideki Hozen
    • 2
  • Hidenao Sasaki
    • 1
  1. 1.Department of NeurologyHokkaido University, Graduate School of MedicineSapporoJapan
  2. 2.Department of NeurologyObihiro Kosei HospitalObihiroJapan