The wide-ranging clinical and genetic features in Japanese families with valosin-containing protein proteinopathy

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 were diagnosed either inclusion body myopathy or amyotrophic lateral sclerosis, 1 patient showed demyelinating polyneuropathy, which was confirmed by longitudinal nerve conduction studies. Sural biopsy revealed intranuclear ubiquitin staining Schwann cells. Three pathogenic mutations (p.Arg191Gln, p.Arg155Cys, and p.Ile126Phe) detected. A novel mutation, c.293 A>T (p.Asp98Val), also identified a sclerosis frontotemporal dementia. This mutation predicted be “deleterious” “disease causing” using silico analyses. In conclusion, polyneuropathy may phenotype caused The p.Asp98Val found proteinopathy. We believe our cases represent wide clinical spectrum