Mutant valosin‐containing protein causes a novel type of frontotemporal dementia

R Schröder, GDJ Watts, SG Mehta, BO Evert… - Annals of …, 2005 - Wiley Online Library
R Schröder, GDJ Watts, SG Mehta, BO Evert, P Broich, K Fließbach, K Pauls, VH Hans…
Annals of neurology, 2005Wiley Online Library
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 …
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. Ann Neurol 2005;57:457–461
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