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

• Cai, Huaying

• Yabe, Ichiro

• Sato, Kazunori

• Kano, Takahiro

• Nakamura, Masakazu

• Hozen, Hideki

• Sasaki, Hidenao

抄録

Previous studies have identified several genetic loci associated with 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 5 genes were sequenced directly. Definite IBM was confirmed in 14 cases, probable IBM in 3 cases, and possible IBM in 4 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 3 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.

収録刊行物

• Journal of neurology

  Journal of neurology 259 (9), 1913-1922, 2012-09

  Springer

キーワード

• Iinclusion body myositis
• Desmin
• UDP-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)

詳細情報

• CRID: 1050564288963066880
• NII論文ID: 120005343757
• ISSN: 14321459
• ISSN: 03405354
• HANDLE: 2115/53470
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles