title: Clinical, pathological, and genetic mutation analysis of sporadic inclusion body myositis in Japanese people.
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.
authors.affiliation: Department of Neurology, Hokkaido University, Graduate School of Medicine, N15W7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Huaying
authors.initials: H
authors.lastname: Cai
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yabe
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sato
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kano
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hideki
authors.initials: H
authors.lastname: Hozen
authors.forename: Hidenao
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D016001:Confidence Intervals; D004252:DNA Mutational Analysis; D003893:Desmin / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D018979:Myositis, Inclusion Body / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D012189:Retrospective Studies; D000074405:Valosin Containing Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D003893:Desmin; C120696:LDB3 protein, human; D060588:LIM Domain Proteins; D009097:Multienzyme Complexes; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase; D000251:Adenosine Triphosphatases; D018995:Myosin Heavy Chains; C000614178:VCP protein, human; D000074405:Valosin Containing Protein