Genotype-phenotype study in patients with valosin-containing protein mutations associated with multisystem proteinopathy.
Mutations in valosin-containing protein (VCP), an ATPase involved in protein degradation and autophagy, cause VCP disease, a progressive autosomal dominant adult onset multisystem proteinopathy. The goal of this study is to examine if phenotypic differences in this disorder could be explained by the specific gene mutations. We therefore studied 231 individuals (118 males and 113 females) from 36 families carrying 15 different VCP mutations. We analyzed the correlation between the different mutations and prevalence, age of onset and severity of myopathy, Paget's disease of bone (PDB), and frontotemporal dementia (FTD), and other comorbidities. Myopathy, PDB and FTD was present in 90%, 42% and 30% of the patients, respectively, beginning at an average age of 43, 41, and 56 years, respectively. Approximately 9% of patients with VCP mutations had an amyotrophic lateral sclerosis (ALS) phenotype, 4% had been diagnosed with Parkinson's disease (PD), and 2% had been diagnosed with Alzheimer's disease (AD). Large interfamilial and intrafamilial variation made establishing correlations difficult. We did not find a correlation between the mutation type and the incidence of any of the clinical features associated with VCP disease, except for the absence of PDB with the R159C mutation in our cohort and R159C having a later age of onset of myopathy compared with other molecular subtypes.
['Al-Obeidi|E|E|', 'Al-Tahan|S|S|', 'Surampalli|A|A|', 'Goyal|N|N|', 'Wang|A K|AK|', 'Hermann|A|A|', 'Omizo|M|M|', 'Smith|C|C|', 'Mozaffar|T|T|', 'Kimonis|V|V|http://orcid.org/0000-0003-1567-4449']
D000328:Adult D017668:Age of Onset D000368:Aged D000544:Alzheimer Disease D000690:Amyotrophic Lateral Sclerosis D015331:Cohort Studies D005192:Family Health D005260:Female D020022:Genetic Predisposition to Disease D005838:Genotype D006801:Humans D008297:Male D008875:Middle Aged D009154:Mutation D010300:Parkinson Disease D010641:Phenotype D000074405:Valosin Containing Protein D055815:Young Adult
genotype-phenotype valosin-containing protein VCP IBMPFD multisystem proteinopathy (MSP)