title: Mutant valosin-containing protein causes a novel type of frontotemporal dementia.
abstract: 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.
authors.affiliation: Department of Neurology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. rolf.schroeder@ukb.uni-bonn.de
authors.forename: Rolf
authors.initials: R
authors.lastname: Schröder
authors.forename: Giles D J
authors.initials: GD
authors.lastname: Watts
authors.forename: Sarju G
authors.initials: SG
authors.lastname: Mehta
authors.forename: Bernd O
authors.initials: BO
authors.lastname: Evert
authors.forename: Petra
authors.initials: P
authors.lastname: Broich
authors.forename: Klaus
authors.initials: K
authors.lastname: Fliessbach
authors.forename: Katharina
authors.initials: K
authors.lastname: Pauls
authors.forename: Volkmar H
authors.initials: VH
authors.lastname: Hans
authors.forename: Virginia
authors.initials: V
authors.lastname: Kimonis
authors.forename: Dietmar R
authors.initials: DR
authors.lastname: Thal
mesh_terms: 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
chemical_list: 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