Abstract
The valosin-containing protein (VCP), a widely expressed protein, controls the ubiquitin-proteasome system, endolysosomal sorting, and autophagy to maintain cellular proteostasis. Frontotemporal dementia (FTD), inclusion body myopathy, and Paget's disease of the bone (PDB) are all caused by dominant missense mutations in the VCP gene, which interfere with these mechanisms and cause a multisystem proteinopathy. We describe phenotypic and genetic findings of five patients with four different mutations in VCP gene (NM_007126): c.278G > A (p.R93H), c.463C > T (p.R155C), c.410C > T (p.P137L), c.464G > A (p.R155H), c.410C > T (p.P137L). We analysed the patient' biopsies, all characterized by a muscular phenotype, and we executed immunofluorescence staining to evaluate the presence of proteins: p62, VCP, desmin, myotilin, TDP-43. Eventually we performed a brief literature review to compare our cases with those already reported. Our report strongly suggest that VCP gene mutations can be related with a predominant skeletal muscle phenotype without any central nervous system involvement, as occasionally reported in the literature. Particularly, our patient with R93H shows only myopathic involvement while this mutation has been described once associated only to Hereditary Spastic Paraplegia. Further study will be necessary to understand such a broad and different clinical spectrum.