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Inclusion body myopathy and frontotemporal dementia caused by a novel VCP mutation

Anna Bersano1, Roberto Del Bo, Costanza Lamperti

  • 1Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ospedale Maggiore Policlinico Mangiagalli and Regina Elena, Via F. Sforza 35, 20122 Milan, Italy.

Neurobiology of Aging
|September 25, 2007
PubMed

Insights

This study identifies a new VCP gene mutation (R159C) linked to hereditary inclusion body myopathy (IBM) and frontotemporal dementia (FTD). The findings suggest genetic testing for VCP mutations in sporadic cases of IBM and FTD.

Area of Science:

  • Genetics
  • Neurology
  • Pathology

Background:

  • Hereditary inclusion body myopathy (IBM) with Paget's disease of the bone (PDB) and frontotemporal dementia (FTD) is a rare autosomal dominant disorder.
  • Mutations in the valosin-containing protein (VCP) gene are the known cause of this syndrome.

Observation:

  • A novel heterozygous VCP gene mutation, R159C, was identified in a 69-year-old Italian patient with a 19-year history of progressive myopathy and subsequent FTD.
  • Muscle biopsy revealed degenerative changes, rimmed vacuoles, and VCP/ubiquitin-positive inclusions.
  • No family history of IBM, PDB, or FTD was reported in the preceding two generations.

Findings:

  • The R159C mutation occurred at a known mutational hotspot in the VCP gene.
  • Histopathological and biochemical evidence supported VCP accumulation in muscle tissue.
  • The patient's clinical presentation of IBM and FTD supports the pathogenic role of the R159C VCP mutation.

Implications:

  • This discovery expands the known spectrum of VCP mutations associated with IBM and FTD.
  • The findings highlight the importance of investigating VCP gene mutations even in patients without a clear family history (sporadic cases).
  • This research contributes to understanding the molecular mechanisms underlying VCP-related disorders.

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