Journal
NEUROBIOLOGY OF AGING
Volume 100, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2020.10.028
Keywords
Valosin-containing protein; Demyelinating polyneuropathy; Inclusion body myopathy; Amyotrophic lateral sclerosis; Frontotemporal dementia
Categories
Funding
- AMED [JP20ek0109488, JP19ek0109284]
- JSPS KAKENHI [19K07973]
- Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP [29-4]
- Grants-in-Aid for Scientific Research [19K07973] Funding Source: KAKEN
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Mutations in the VCP gene can cause various neurodegenerative disorders, including inclusion body myopathy and amyotrophic lateral sclerosis. This study identified that VCP missense mutations can also lead to demyelinating polyneuropathy, characterized by nerve conduction abnormalities.
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 fronto-temporal 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. (C) 2020 Elsevier Inc. All rights reserved.
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