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Autosomal dominant inclusion body myopathy, Paget disease of bone, and frontotemporal dementia.
- Source :
-
Alzheimer disease and associated disorders [Alzheimer Dis Assoc Disord] 2005 Oct-Dec; Vol. 19 Suppl 1, pp. S44-7. - Publication Year :
- 2005
-
Abstract
- Autosomal dominant proximal limb girdle or inclusion body myopathy, associated with Paget disease of bone and frontotemporal dementia (IBMPFD) is a recently described disorder that maps to chromosome 9p21.1-p12. We refined the critical locus and identified the gene as the Valosin Containing Protein (VCP) gene, a member of the AAA-ATPase superfamily using a candidate gene approach. Six missense mutations were found to co-segregate with affected individuals only, two of these representing mutation hot spots. We report the clinical and molecular findings in 99 individuals in 13 families. VCP is associated with a variety of cellular activities, including the control of cell cycle, membrane fusion, and the ubiquitin-proteasome degradation pathway. Previous studies have associated VCP mutants in cell lines with vacuole formation and aggregate formation. Identification of VCP as the gene causing IBMPFD has important implications for understanding the pathogenesis of neurodegenerative disorders.
- Subjects :
- Adenosine Triphosphatases
Adolescent
Adult
Child
Child, Preschool
Chromosome Mapping
Chromosomes, Human, Pair 9 genetics
Female
Humans
Male
Middle Aged
Myositis, Inclusion Body pathology
Osteitis Deformans pathology
Pick Disease of the Brain pathology
Valosin Containing Protein
Cell Cycle Proteins genetics
Mutation, Missense genetics
Myositis, Inclusion Body genetics
Osteitis Deformans genetics
Pick Disease of the Brain genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0893-0341
- Volume :
- 19 Suppl 1
- Database :
- MEDLINE
- Journal :
- Alzheimer disease and associated disorders
- Publication Type :
- Academic Journal
- Accession number :
- 16317258
- Full Text :
- https://doi.org/10.1097/01.wad.0000183081.76820.5a