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Mutant valosin‐containing protein causes a novel type of frontotemporal dementia
Author(s) -
Schröder Rolf,
Watts Giles D. J.,
Mehta Sarju G.,
Evert Bernd O.,
Broich Petra,
Fließbach Klaus,
Pauls Katharina,
Hans Volkmar H.,
Kimonis Virginia,
Thal Dietmar R.
Publication year - 2005
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20407
Subject(s) - frontotemporal dementia , missense mutation , mutant protein , mutant , ubiquitin , dementia , mutation , biology , medicine , genetics , pathology , gene , disease
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. Ann Neurol 2005;57:457–461