Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein

Watts, Giles D J, Wymer, Jill, Kovach, Margaret J, Mehta, Sarju G, Mumm, Steven, Darvish, Daniel, Pestronk, Alan, Whyte, Michael P and Kimonis, Virginia E (2004) Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nature Genetics, 36 (4). pp. 377-81. ISSN 1061-4036

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Abstract

Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD) is a dominant progressive disorder that maps to chromosome 9p21.1-p12. We investigated 13 families with IBMPFD linked to chromosome 9 using a candidate-gene approach. We found six missense mutations in the gene encoding valosin-containing protein (VCP, a member of the AAA-ATPase superfamily) exclusively in all 61 affected individuals. Haplotype analysis indicated that descent from two founders in two separate North American kindreds accounted for IBMPFD in approximately 50% of affected families. VCP is associated with a variety of cellular activities, including cell cycle control, membrane fusion and the ubiquitin-proteasome degradation pathway. Identification of VCP as causing IBMPFD has important implications for other inclusion-body diseases, including myopathies, dementias and Paget disease of bone (PDB), as it may define a new common pathological ubiquitin-based pathway.

Item Type: Article
Uncontrolled Keywords: adenosine triphosphatases,cell cycle proteins,chromosome mapping,chromosomes, human, pair 9,female,humans,immunohistochemistry,male,muscular diseases,mutation,osteitis deformans,pedigree
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 27 Jan 2014 13:18
Last Modified: 21 Apr 2020 22:40
URI: https://ueaeprints.uea.ac.uk/id/eprint/46868
DOI: 10.1038/ng1332

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