Giles Watts is particularly interested in inherited muscle disorders that occur in combination with diseases of bone. Families with a combination of muscle disease, Paget disease of bone, and dementia (also known as IBMPFD) have been studied in the laboratory, and the gene for the disorder has been localized to chromosome 9. By identifying the causal gene (VCP, CDC48 or p97) for this disorder, the researchers are now identifying the key pathways and functions that are disrupted by the mutations they have found in the affected families.
The Watts group is studying additional members of the original families and additional families with the combination of muscle and bone disease and are looking at the relationship between the familial disorders and the individuals' genetic makeup. They are also looking for other disorders that have various combinations of muscle, bone and brain disease, which may be related to IBMPFD and result from mutations in genes that are part of the VCP pathways.
Identifying the single gene responsible for IBMPFD could have implications in many disciplines, leading to greater understanding of inclusion body myopathy, dementia and Paget disease of the bone. These findings may not only make it possible to develop better clinical treatments for families with IBMPFD, but also for those with other sporadic and hereditary diseases that share components of IBMPFD.
- 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.
- Hunermund G, Schirmacher A, Ringelstein B, Young P, Watts GD, Meuleman J, Nelis E, Chance PF, Timmerman V, Stogbauer F, Kuhlenbaumer G. Genomic organization and mutation analysis of three candidate genes for hereditary neuralgic amyotrophy. Muscle Nerve. 2004 Apr;29(4):601-4.
- Watts GD, Thorne M, Kovach MJ, Pestronk A, Kimonis VE. Clinical and genetic heterogeneity in chromosome 9p associated hereditary inclusion body myopathy: exclusion of GNE and three other candidate genes. Neuromuscul Disord. 2003 Sep;13(7-8):559-67.
- Watts GD, O'Briant KC, Chance PF. Evidence of a founder effect and refinement of the hereditary neuralgic amyotrophy (HNA) locus on 17q25 in American families. Hum Genet. 2002 Feb;110(2):166-72. Epub 2001 Dec 18.
- Jeannet PY, Watts GD, Bird TD, Chance PF. Craniofacial and cutaneous findings expand the phenotype of hereditary neuralgic amyotrophy. Neurology. 2001 Dec 11;57(11):1963-8.
- Watts GD, O'Briant KC, Borreson TE, Windebank AJ, Chance PF. Evidence for genetic heterogeneity in hereditary neuralgic amyotrophy. Neurology. 2001 Mar 13;56(5):675-8.