Inclusion body myopathy and frontotemporal dementia caused by a novel VCP mutation.
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.
Bersano
Anna
A
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.
Del Bo
Roberto
R
Lamperti
Costanza
C
Ghezzi
Serena
S
Fagiolari
Gigliola
G
Fortunato
Francesco
F
Ballabio
Elena
E
Moggio
Maurizio
M
Candelise
Livia
L
Galimberti
Daniela
D
Virgilio
Roberta
R
Lanfranconi
Silvia
S
Torrente
Yvan
Y
Carpo
Marinella
M
Bresolin
Nereo
N
Comi
Giacomo P
GP
Corti
Stefania
S
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
D018797:Cell Cycle Proteins; D005819:Genetic Markers; D025801:Ubiquitin; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein