Valosin-Containing Protein-Related Disorders via the VCP Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesPrice Test CPT CodeGene CPT Codes Copy CPT Codes STAT Prenatal
4807 VCP$640 8147981479,81479 Add to Order

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

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Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Inclusion body myopathy with early onset Paget disease and frontotemporal dementia (IBMPFD, OMIM 167320) is characterized by adult-onset proximal and distal muscle weakness, early onset Paget disease of bone, and frontotemporal dementia (Kimonis et al. GeneReviews 2011). Muscle weakness resembles that see in limb-girdle muscular dystrophy, and respiratory and cardiac involvement may occur later in the disease course. Serum CK is typically normal or mildly elevated and EMG studies demonstrate myopathic changes (Kimonis et al. Genet Med 2:232-241, 2000). Symptoms of bone disease include pain of the spine and hip and enlargement and deformity of the long bones. Bone symptoms originate from focal abnormalities of increased bone turnover (Kimonis et al. Am J Med Genet 146A:745-757, 2008). Serum alkaline phosphatase levels are elevated as are urine pyridinoline and deoxypyridinoline concentrations. Early signs of frontotemporal dementia include social unawareness and disinhibition, expressive or receptive language dysfunction, and relative sparing of memory (Kimonis et al. GeneReviews 2011). IBMPFD is a progressive disease leading to disabling muscle and bone disease and inability to speak. An exome sequencing strategy revealed that familial amyotrophic lateral sclerosis with or without frontotemporal dementia (ALS14, OMIM 613954) results from mutations in the VCP gene (Johnson et al. Neuron 68:857-864, 2010).

Genetics

Inclusion body myopathy with early onset Paget disease and frontotemporal dementia is an autosomal dominant disorder with incomplete penetrance of the three clinical features (limb-girdle muscle weakness, Paget disease of bone, and frontotemporal dementia). Missense mutation of the VCP gene (OMIM 601023) are the only known cause of IBMPFD, and substitution of the Arg155 residue was shown to be the predominant mutation among North American patients (Watts et al. Nat Genet 36:377-381, 2004). ALS14 is also an autosomal dominant disorder.

Testing Strategy

This test provides full coverage of all coding exons of the VCP gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Clinical Sensitivity - Sequencing and CNV

Sensitivity should be high in patients meeting clinical criteria for all three symptoms of IBMPFD. In one study, 10 of 13 affected families had a mutation involving Arg155 (Watts et al. Nat Genet 36:377-381, 2004). VCP mutations are probably a rare cause of ALS. Screening of the VCP gene in 210 familial ALS cases and 78 autopsy-proven ALS cases identified 3 mutations in 4 patients (Johnson et al. Neuron 68:857-864, 2010).

Indications for Test

Patients with late onset and progressive proximal and distal muscle weakness, Paget disease of bone, and premature frontotemporal dementia.

Gene

Official Gene Symbol OMIM ID
VCP 601023
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Johnson, J. O., et.al. (2010). "Exome sequencing reveals VCP mutations as a cause of familial ALS." Neuron 68(5): 857-64. PubMed ID: 21145000
  • Kimonis, V. E., et.al. (2000). "Clinical and molecular studies in a unique family with autosomal dominant limb-girdle muscular dystrophy and Paget disease of bone." Genet Med 2(4): 232-41. PubMed ID: 11252708
  • Kimonis, V. E., et.al. (2008). "Clinical studies in familial VCP myopathy associated with Paget disease of bone and frontotemporal dementia." Am J Med Genet A 146A(6): 745-57. PubMed ID: 18260132
  • Kimonis, Virginia (2011). "Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia."
  • Watts, G. D., et.al. (2004). "Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein." Nat Genet 36(4): 377-81. PubMed ID: 15034582

Ordering/Specimens

Ordering Options

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
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Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

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Specimen Types

Specimen Requirements and Shipping Details

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