DISEASE CLASSIFICATION(S):
Amyotrophic Lateral Sclerosis(ALS)
Facioscapulohumeral Muscular Dystrophy(FSHD)
Inclusion-Body Myositis(IBM)
Limb-Girdle Muscular Dystrophy(LGMD)
NAME OF CLINICAL TRIAL/STUDY:
Neuromuscular Disease Linked to Chromosome 9 with Paget Disease of Bone - Gene Identification
TRIAL RESULTS:
4/04:
The researchers, who received MDA support, found that the gene that, when flawed, leads to the development of an inclusion-body muscle disease, Paget’s disease of bone, and frontotemporal dementia is the gene for valosin-containing protein (VCP). This gene, located on chromosome 9, carries instructions for a protein that participates in a variety of cellular activities, including how the cell disposes of unwanted substances. The results are published in the April 2004 issue of Nature Genetics.
TRIAL UPDATES:
9/03:
In a paper published in the September 2003 issue of Neuromuscular Disorders, the researchers show that they have ruled out any connection between this condition and mutations in GNE, a chromosome 9 gene that can lead to inclusion-body myositis (IBM). They also ruled out a connection to three other genes.
PURPOSE AND RATIONALE:
The investigators are requesting the participation of families with the combination of chromosome-9-linked neuromuscular disease with inclusion bodies associated with Paget disease of bone with or without frontotemporal dementia.
Paget disease is a disorder associated with pain in the bones and characteristic X-ray findings.
Frontotemporal dementia involves language-related deficits, such difficulty naming things or inability to speak; personality changes, such as apathy or agitation; possible auditory or visual hallucinations.
The investigators have identified five large families with this combination and have noted frontotemporal dementia in approximately one-third of the family members.
As a result of linkage studies, they have previously localized the gene for this unusual disorder to a region on chromosome 9. The disease in these families has been diagnosed as inclusion-body myopathy, ALS-like disease and facioscapulohumeral muscular dystrophy. Additional families with this disorder will allow the group to further characterize the clinical features and to identify the genetic mutation or mutations responsible for this combination of abnormalities. The hope is that this will permit better diagnostic and treatment options in the future.
OPENING DATES:
Nov 15 1999
TARGET NUMBER OF PARTICIPANTS:
Unlimited
RECRUITMENT STATUS:
Closed
ELIGIBILITY REQUIREMENTS:
Must have received a diagnosis of or have a family history of muscular dystrophy or similar muscle disorder with inclusion bodies and have Paget disease of bone.
The only invasive procedure is a blood test. The investigators will travel to the participants.
PUBLICATIONS:
1. Kimonis, V. E.; Kovach, M. J.; Waggoner, B.; Leal, S.; Salam, A.; Rimer, L.; Davis, K.; Khardori, R.; Gelber, D. Clinical and molecular studies in a unique family with autosomal dominant limb-girdle muscular dystrophy and Paget disease of bone. Genet. Med. 2: 232-241, 2000. Pub Med Report
2. Kovach, M.J.; Waggoner, B.; Suzanne M. Leal, S.M.; et al. Clinical delineation and localization to chromosome 9p13.3-p12 of a unique dominant disorder: Hereditary inclusion body myopathy, Paget disease of bone and frontotemporal dementia in four families. Molecular Genetics and Metabolism, 2001. 74:458-475. Pub Med Report
3. Waggoner, B.; Kovach, M. J.; Winkelman, M.; Cai, D.; Khardori, R.; Gelber, D.; Kimonis, V. E. Heterogeneity in familial dominant Paget disease of bone and muscular dystrophy. Am. J. Med. Genet. 108: 187-191, 2002. Pub Med Report
4. Watts, D.J.; Thorne, M.; Kovach, M.J.; Pestronk, A.; and Kimonis, V.E. Clinical and genetic heterogeneity in chromosome 9p associated hereditary inclusion body myopathy: exclusion of GNE and three other candidate genes. Neuromuscular Disorders, vol. 13, nos 7-8, Sept. 2003, pp. 559-567. Pub Med Report
5. Watts, G.D.; Wymer, J.; Kovach, M.J.; Mehta, S.G.; Mumm, S.; Darvish, D.; Pestronk, A.; Whyte, M.P; and Kimonis, V.E. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nature Genetics, vol. 36, no. 4, April 2004, pp. 377-381. Pub Med Report
