A novel exon 2 I27V VCP variant is associated with dissimilar clinical syndromes

J Neurol. 2011 Aug;258(8):1494-6. doi: 10.1007/s00415-011-5966-4. Epub 2011 Mar 9.


Mutations in valosin-containing protein (VCP) are associated with a syndromic constellation of inclusion body myositis, Paget's disease of bone and frontotemporal dementia. Here we describe the case reports of two patients with a novel variation (p.I27V) in the VCP gene that was not identified in a healthy control population. One patient presented with a frontotemporal dementia syndrome associated with raised serum alkaline phosphatase and a family history of progressive muscle disease and behavioural decline, while the second patient presented with isolated progressive dysarthria. Together these cases suggest a potential for the same VCP mutation to produce distinct patterns of brain damage, underlining the clinical heterogeneity of VCP-associated disease.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Aged
  • Cell Cycle Proteins / genetics*
  • Dysarthria / genetics*
  • Dysarthria / physiopathology
  • Exons / genetics
  • Female
  • Frontotemporal Dementia / genetics*
  • Frontotemporal Dementia / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Valosin Containing Protein


  • Cell Cycle Proteins
  • Adenosine Triphosphatases
  • VCP protein, human
  • Valosin Containing Protein