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

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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.

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Acknowledgments

We thank Miss Rumiko Ochi and Miss Manami Watanabe for their contributions to the investigations of muscle pathology and immunology. We are grateful to Dr. Kouji Shima (Sapporo Neurology Clinic) for advising on this study. Finally, we thank all patients and control subjects for their active cooperation. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture, Japan.

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Authors and Affiliations

  1. Department of Neurology, Hokkaido University, Graduate School of Medicine, N15W7, Kita-ku, Sapporo, 060-8638, Japan

    Huaying Cai, Ichiro Yabe, Kazunori Sato, Takahiro Kano, Masakazu Nakamura & Hidenao Sasaki

  2. Department of Neurology, Obihiro Kosei Hospital, Obihiro, Japan

    Hideki Hozen

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  1. Huaying Cai
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  2. Ichiro Yabe
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Correspondence to Ichiro Yabe.

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Cai, H., Yabe, I., Sato, K. et al. Clinical, pathological, and genetic mutation analysis of sporadic inclusion body myositis in Japanese people. J Neurol 259, 1913–1922 (2012). https://doi.org/10.1007/s00415-012-6439-0

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  • DOI: https://doi.org/10.1007/s00415-012-6439-0

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