Description:
INCLUSION BODY MYOPATHY WITH EARLY-ONSET PAGET DISEASE AND FRONTOTEMPORAL DEMENTIA; IBMPFD
VALOSIN-CONTAINING PROTEIN; VCP
|
Repository
|
NIGMS Human Genetic Cell Repository
|
| Subcollection |
Heritable Diseases |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
|
Biopsy Source
|
Peripheral vein
|
|
Cell Type
|
B-Lymphocyte
|
|
Tissue Type
|
Blood
|
|
Transformant
|
Epstein-Barr Virus
|
|
Sample Source
|
DNA from LCL
|
|
Race
|
White
|
|
Family Member
|
1
|
|
Relation to Proband
|
proband
|
|
Confirmation
|
Molecular characterization before cell line submission to CCR
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin confirmed by LINE assay |
| |
| alkaline phosphatase |
According to the submitter biochemical test results for this subject showed increased enzyme activity. EC Number: 3.1.3.1 |
| |
| Gene |
VCP |
| Chromosomal Location |
9p13-p12 |
| Allelic Variant 1 |
601023.0001; INCLUSION BODY MYOPATHY WITH EARLY-ONSET PAGET DISEASE AND FRONTOTEMPORAL DEMENTIA |
| Identified Mutation |
ARG155HIS; In 7 of 13 families with autosomal dominant IBMPFD (167320), Watts et al. (Nature Genet 36:377-381, 2004) identified a G-to-A transition at nucleotide 464 of the VCP gene, resulting in an arg155-to-his substitution (R155H). This mutation appears to have arisen independently on several haplotype backgrounds.
|
| Remarks |
Clinically affected; myopathy with onset at 33 years of age; Paget disease with onset at 37 years of age; serum creatine phosphokinase is 192 U/L; serum bone-specific alkaline phosphatase is 127 U/L; radiographs show slight enlargement of the vertebral body (T10) in the thoracic spine, as well as sclerotic changes, enlargement and picture framing of a vetebral body (L3) in the lumbar spine; donor subject is heterozygous for a G>A transition at nucleotide 464 in exon 5 of the VCP gene (464G>A) resulting in the substitution of histidine for arginine at codon 155 [Arg155His(R155H)]; see GM21829 Fibroblast |
| 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 Nature genetics36:377-81 2004 |
| PubMed ID: 15034582 |
| |
| Kovach MJ, Waggoner B, Leal SM, Gelber D, Khardori R, Levenstien MA, Shanks CA, Gregg G, Al-Lozi MT, Miller T, Rakowicz W, Lopate G, Florence J, Glosser G, Simmons Z, Morris JC, Whyte MP, Pestronk A, Kimonis VE, Clinical delineation and localization to chromosome 9p133-p12 of a unique dominant disorder in four families: hereditary inclusion body myopathy, Paget disease of bone, and frontotemporal dementia Molecular genetics and metabolism74:458-75 2001 |
| PubMed ID: 11749051 |
| |
| Kimonis VE, Kovach MJ, Waggoner B, Leal S, Salam A, Rimer L, Davis K, Khardori R, and Gelber D.
, Clinical and molecular studies in a unique family with autosomal dominant limb-girdle muscular dystrophy and Paget disease of bone Genetics in Medicine2(4):232-241 2000 |
| PubMed ID: 11252708 |
|
|