Mutant valosin-containing protein causes a novel type of frontotemporal dementia.
Mutations in the valosin-containing protein (VCP) gene on chromosome 9p13-p12 recently have been shown to cause autosomal dominant inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia. Here, we report the central nervous system autopsy findings in a 55-year-old German patient with inclusion body myopathy and frontotemporal dementia who harbors a heterozygous R155C missense mutation residing in the N-terminal CDC48 domain of VCP, which is involved in ubiquitin binding. We demonstrate that mutant VCP causes a novel type of frontotemporal dementia characterized by neuronal nuclear inclusions containing ubiquitin and VCP.
Schröder
Rolf
R
Department of Neurology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. rolf.schroeder@ukb.uni-bonn.de
Watts
Giles D J
GD
Mehta
Sarju G
SG
Evert
Bernd O
BO
Broich
Petra
P
Fliessbach
Klaus
K
Pauls
Katharina
K
Hans
Volkmar H
VH
Kimonis
Virginia
V
Thal
Dietmar R
DR
D000251:Adenosine Triphosphatases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001120:Arginine / Q000235:genetics; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D003704:Dementia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D020125:Mutation, Missense; D013194:Staining and Labeling / Q000379:methods; D025801:Ubiquitin / Q000378:metabolism; D000074405:Valosin Containing Protein; D016875:tau Proteins / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D018797:Cell Cycle Proteins; D005904:Glial Fibrillary Acidic Protein; D025801:Ubiquitin; D016875:tau Proteins; D001120:Arginine; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein; D003545:Cysteine