Genotype-phenotype study in patients with valosin-containing protein mutations associated with multisystem proteinopathy
| Autor: | Al-Obeidi, E., Al-Tahan, S., Surampalli, A., Goyal, N., Wang, A. K., Hermann, A., Omizo, M., Smith, C., Mozaffar, T., Kimonis, V. |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Genotype genetics [Alzheimer Disease] genetics [Valosin Containing Protein] Article Cohort Studies Young Adult genetics [Parkinson Disease] Alzheimer Disease Valosin Containing Protein Humans Genetic Predisposition to Disease ddc:610 genetics [Genetic Predisposition to Disease] Age of Onset Aged Family Health valosin-containing protein Amyotrophic Lateral Sclerosis Parkinson Disease Middle Aged multisystem proteinopathy (MSP) IBMPFD genotype-phenotype genetics [Amyotrophic Lateral Sclerosis] Phenotype Mutation Female VCP |
| Zdroj: | Al-Obeidi, E; Al-Tahan, S; Surampalli, A; Goyal, N; Wang, AK; Hermann, A; et al.(2018). Genotype-phenotype study in patients with valosin-containing protein mutations associated with multisystem proteinopathy. CLINICAL GENETICS, 93(1), 119-125. doi: 10.1111/cge.13095. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/2vs1j696 Clinical genetics 93(1), 119-125 (2017). doi:10.1111/cge.13095 |
| DOI: | 10.1111/cge.13095. |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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