Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein.
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Watts GD, Wymer J, Kovach MJ, Mehta SG, Mumm S, Darvish D, Pestronk A, Whyte MP, Kimonis VE
Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein.
Nat Genet. 2004 Apr;36(4):377-81. Epub 2004 Mar 21.
- PubMed ID
- 15034582 [ View in PubMed]
- 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.