title: Frontotemporal dementia caused by CHMP2B mutations.
abstract: CHMP2B mutations are a rare cause of autosomal dominant frontotemporal dementia (FTD). The best studied example is frontotemporal dementia linked to chromosome 3 (FTD-3) which occurs in a large Danish family, with a further CHMP2B mutation identified in an unrelated Belgian familial FTD patient. These mutations lead to C-terminal truncations of the CHMP2B protein and we will review recent advances in our understanding of the molecular effects of these mutant truncated proteins on vesicular fusion events within the endosome-lysosome and autophagy degradation pathways. We will also review the clinical features of FTD caused by CHMP2B truncation mutations as well as new brain imaging and neuropathological findings. Finally, we collate the current data on CHMP2B missense mutations, which have been reported in FTD and motor neuron disease.
authors.affiliation: Department of Neurodegenerative Disease, VCL Institute of Neurology, Queen Square, London, UK. la.isaacs@prion.ucl.ac.uk
authors.forename: A M
authors.initials: AM
authors.lastname: Isaacs
authors.forename: P
authors.initials: P
authors.lastname: Johannsen
authors.forename: I
authors.initials: I
authors.lastname: Holm
authors.forename: J E
authors.initials: JE
authors.lastname: Nielsen
mesh_terms: D000595:Amino Acid Sequence; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics*; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: C503812:CHMP2B protein, human; D056827:Endosomal Sorting Complexes Required for Transport