title: Inclusion body myopathy and frontotemporal dementia caused by a novel VCP mutation.
abstract: Hereditary inclusion body myopathy (IBM) with Paget's disease of the bone (PDB) and frontotemporal dementia (FTD) is a rare autosomal dominant disease caused by mutations in the valosin-containing protein (VCP) gene. We report a novel heterozygous VCP gene mutation (R159C) in a 69-year-old Italian patient presenting with slowly progressive muscle weakness of the distal upper and proximal lower limbs since the age of 50 years, 18 years later FTD supervened. No dementia or myopathies were revealed in the family history covering two generations. Degenerative changes and rimmed vacuoles together with VCP- and ubiquitin-positive cytoplasmic and nuclear aggregates were observed at the muscle biopsy. Several elements support the pathogenic role of the R159C VCP gene mutation: the occurrence at the same codon of a different, previously identified pathogenic mutation within a VCP gene mutational hot-spot, the histopathological and biochemical evidence of muscle VCP accumulation and the combined clinical presentation of IBM and FTD. These findings suggest VCP gene investigation even in apparently sporadic cases.
authors: Dino 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.
authors: Anna
authors: A
authors: Bersano
authors: Roberto
authors: R
authors: Del Bo
authors: Costanza
authors: C
authors: Lamperti
authors: Serena
authors: S
authors: Ghezzi
authors: Gigliola
authors: G
authors: Fagiolari
authors: Francesco
authors: F
authors: Fortunato
authors: Elena
authors: E
authors: Ballabio
authors: Maurizio
authors: M
authors: Moggio
authors: Livia
authors: L
authors: Candelise
authors: Daniela
authors: D
authors: Galimberti
authors: Roberta
authors: R
authors: Virgilio
authors: Silvia
authors: S
authors: Lanfranconi
authors: Yvan
authors: Y
authors: Torrente
authors: Marinella
authors: M
authors: Carpo
authors: Nereo
authors: N
authors: Bresolin
authors: Giacomo P
authors: GP
authors: Comi
authors: Stefania
authors: S
authors: Corti
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D017668:Age of Onset; D000368:Aged; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D003704:Dementia / Q000150:complications / Q000235:genetics*; D018450:Disease Progression; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D018908:Muscle Weakness / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D018979:Myositis, Inclusion Body / Q000150:complications / Q000235:genetics*; D025801:Ubiquitin / Q000378:metabolism; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D005819:Genetic Markers; D025801:Ubiquitin; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein