UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro

van der Zee, J; Urwin, H; Engelborghs, S; Bruyland, M; Vandenberghe, R; Dermaut, B; De Pooter, T; ... Van Broeckhoven, C; + view all (2008) CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro. HUM MOL GENET , 17 (2) 313 - 322. 10.1093/hmg/ddm309.

Full text not available from this repository.

Abstract

The charged multivesicular body protein 2B gene (CHMP2B) was recently associated with frontotemporal lobar degeneration (FTLD) linked to chromosome 3 in a Danish FTLD family (FTD-3). In this family, a mutation in the acceptor splice site of exon 6 produced two aberrant transcripts predicting two C-truncated CHMP2B proteins due to a read through of intron 5 (p.Met178ValfsX2) and a cryptic splicing event within exon 6 (p.Met178LeufsX30). Extensive mutation analysis of CHMP2B in Belgian patients (N = 146) identified one nonsense mutation in exon 5 (c.493C > T) in a familial FTLD patient, predicting a C-truncated protein p.Gln165X analogous to the Danish mutant proteins. Overexpression of Belgian p.Gln165X in human neuroblastoma SK-N-SH cells showed the formation of large, aberrant endosomal structures that were highly similar to those observed for Danish p.Met178ValfsX2. Together, these data suggest that C-truncating mutations in CHMP2B might underlie the pathogenic mechanism in FTLD by disturbing endosome function. We also describe a missense mutation in exon 5 of CHMP2B (p.Asn143Ser) in a familial patient with cortical basal degeneration. However, the pathogenic character of this mutation remains elusive.

Type: Article
Title: CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro
DOI: 10.1093/hmg/ddm309
Keywords: PROGRESSIVE SUPRANUCLEAR PALSY, ESCRT-III, CORTICOBASAL DEGENERATION, DEMENTIA, COMPLEX, CHROMOSOME-3, DIAGNOSIS, CRITERIA, DISEASE, DOMAIN
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Neurodegenerative Diseases
URI: http://discovery.ucl.ac.uk/id/eprint/146125
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item