@article{bbcb620418ad43ef825e9c9eb72d0bc4,
title = "Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein",
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 ∼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.",
author = "Watts, {Giles D.J.} and Jill Wymer and Kovach, {Margaret J.} and Mehta, {Sarju G.} and Steven Mumm and Daniel Darvish and Alan Pestronk and Whyte, {Michael P.} and Kimonis, {Virginia E.}",
note = "Funding Information: We thank the families and their physicians, in particular F. Singer, S. Markus, K. Boycott, B. Sundaram, S. Tucker, Z. Simmons, J. Towfighi, E. Neilan, C. Smith and G. Umberger, for their participation in and contribution to our research studies; C.C. Li for the VCP antibody; S. Banze and M. Geimer for molecular analyses; B. Waggoner for her preliminary work; and L. Kunkel, A. Beggs, E. Gussoni and M. Irons for their support. Funding of this study is from the US National Institutes of Health, the Muscular Dystrophy Association and the Paget Foundation, Children{\textquoteright}s Hospital Boston Equipment Grant, Shriners Hospitals for Children, the Barnes-Jewish Hospital Foundation and previously from the Excellence in Academic Medicine Program at Southern Illinois University School of Medicine.",
year = "2004",
month = apr,
doi = "10.1038/ng1332",
language = "English",
volume = "36",
pages = "377--381",
journal = "Nature Genetics",
issn = "1061-4036",
number = "4",
}