Mutations in the valosin-containing protein (VCP) gene are known to cause various neurodegenerative disorders. Here, we report 8 Japanese patients [6 men, 2 women; median age at onset: 49.5 (range, 35-58) years] from 5 unrelated families with VCP missense mutations. Although 7 of 8 patients were diagnosed with either inclusion body myopathy or amyotrophic lateral sclerosis, 1 patient showed demyelinating polyneuropathy, which was confirmed by longitudinal nerve conduction studies. Sural nerve biopsy of the patient revealed intranuclear ubiquitin staining in Schwann cells. Three known pathogenic VCP mutations (p.Arg191Gln, p.Arg155Cys, and p.Ile126Phe) were detected. A novel mutation, c.293 A>T (p.Asp98Val), was also identified in a patient with amyotrophic lateral sclerosis and frontotemporal dementia. This mutation was predicted to be "deleterious" or "disease causing" using in silico mutation analyses. In conclusion, demyelinating polyneuropathy may be a novel phenotype caused by VCP mutations. The p.Asp98Val mutation was found to be a novel pathogenic mutation of VCP proteinopathy. We believe our cases represent a wide clinical spectrum of VCP mutations.

中文翻译：

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日本含valosin蛋白蛋白病家族的广泛临床和遗传特征

已知含 valosin 蛋白 (VCP) 基因的突变会导致各种神经退行性疾病。在这里，我们报告了 8 名日本患者 [6 名男性，2 名女性；发病年龄中位数：49.5（范围，35-58）岁]来自 5 个具有 VCP 错义突变的无关家族。尽管 8 名患者中有 7 名被诊断为包涵体肌病或肌萎缩侧索硬化，但 1 名患者表现为脱髓鞘性多发性神经病，这通过纵向神经传导研究得到证实。患者的腓肠神经活检显示雪旺细胞核内泛素染色。检测到三个已知的致病性 VCP 突变（p.Arg191Gln、p.Arg155Cys 和 p.Ile126Phe）。在患有肌萎缩侧索硬化和额颞叶痴呆的患者中还发现了一个新的突变，c.293 A>T (p.Asp98Val)。这种突变被预测为“