title: Distinct distal myopathy phenotype caused by VCP gene mutation in a Finnish family.
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.
authors.affiliation: Neuromuscular Research Unit, Department of Neurology, University Hospital and University of Tampere, Finland. johanna.palmio@uta.fi
authors.forename: Johanna
authors.initials: J
authors.lastname: Palmio
authors.forename: Satu
authors.initials: S
authors.lastname: Sandell
authors.forename: Tiina
authors.initials: T
authors.lastname: Suominen
authors.forename: Sini
authors.initials: S
authors.lastname: Penttilä
authors.forename: Olayinka
authors.initials: O
authors.lastname: Raheem
authors.forename: Peter
authors.initials: P
authors.lastname: Hackman
authors.forename: Sanna
authors.initials: S
authors.lastname: Huovinen
authors.forename: Hannu
authors.initials: H
authors.lastname: Haapasalo
authors.forename: Bjarne
authors.initials: B
authors.lastname: Udd
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D018797:Cell Cycle Proteins / Q000235:genetics*; D003937:Diagnosis, Differential; D049310:Distal Myopathies / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D005387:Finland; D006801:Humans; D008297:Male; D008875:Middle Aged; D009136:Muscular Dystrophies / Q000175:diagnosis; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein