Distinct distal myopathy phenotype caused by VCP gene mutation in a Finnish family

Neuromuscular Research Unit, Department of Neurology, University Hospital and University of Tampere, Finland.
Neuromuscular Disorders (Impact Factor: 2.64). 06/2011; 21(8):551-5. DOI: 10.1016/j.nmd.2011.05.008
Source: PubMed

ABSTRACT Inclusion body myopathy with Paget disease and frontotemporal dementia (IBMPFD) is caused by mutations in the valosin-containing protein (VCP) gene. We report a new distal phenotype caused by VCP gene mutation in a Finnish family with nine affected members in three generations. Patients had onset of distal leg muscle weakness and atrophy in the anterior compartment muscles after age 35, which caused a foot drop at age 50. None of the siblings had scapular winging, proximal myopathy, cardiomyopathy or respiratory problems during long-term follow-up. Three distal myopathy patients developed rapidly progressive dementia, became bedridden and died of cachexia and pneumonia and VCP gene mutation P137L (c.410C>T) was then identified in the family. Late onset autosomal dominant distal myopathy with rimmed vacuolar muscle pathology was not sufficient for exact diagnosis in this family until late-occurring dementia provided the clue for molecular diagnosis. VCP needs to be considered in the differential diagnostic work-up in patients with distal myopathy phenotype.

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    • "A key component of the ERAD pathway is VCP which, among others, retro-translocates unfolded proteins from the ER into the cytosol for degradation by the UPS [43]. Primary mutations in VCP cause a muscle disease with rimmed vacuolar pathology [44], [45]. VCP has also been reported to regulate ubiquitin-containing autophagosome maturation during myopathic proteomic stress [30], [31], and may therefore be involved in autophagosomal activation in TMD muscle. "
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