title: A novel presenilin 1 mutation associated with Pick's disease but not beta-amyloid plaques.
abstract: Familial forms of frontotemporal dementia (FTD) with tauopathy are mostly caused by mutations in the gene encoding the microtubule-associated protein tau (MAPT). However, rare forms of familial tauopathy without MAPT mutations have been reported, suggesting other tauopathy-related genetic defects. Interestingly, two presenilin 1 (PS1) mutations (Leu113Pro and insArg352) recently have been associated with familial FTD albeit without neuropathological confirmation. We report here a novel PS1 mutation in a patient with Pick-type tauopathy in the absence of extracellular beta-amyloid deposits. The mutation is predicted to substitute Gly-->Val at codon position 183 (Gly183Val) and to affect the splice signal at the junction of the sixth exon and intron. Further clinical-genetic investigation showed a positive family history of FTD-like dementia and suggested that Gly183Val is associated with a phenotypically heterogeneous neurodegenerative disorder. Our results suggest PS1 as a candidate gene for Pick-type tauopathy without MAPT mutations.
authors.affiliation: Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Dermaut
authors.forename: Samir
authors.initials: S
authors.lastname: Kumar-Singh
authors.forename: Sebastian
authors.initials: S
authors.lastname: Engelborghs
authors.forename: Jessie
authors.initials: J
authors.lastname: Theuns
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.forename: Jos
authors.initials: J
authors.lastname: Saerens
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Pickut
authors.forename: Karin
authors.initials: K
authors.lastname: Peeters
authors.forename: Marleen
authors.initials: M
authors.lastname: van den Broeck
authors.forename: Krist'l
authors.initials: K
authors.lastname: Vennekens
authors.forename: Stephen
authors.initials: S
authors.lastname: Claes
authors.forename: Marc
authors.initials: M
authors.lastname: Cruts
authors.forename: Patrick
authors.initials: P
authors.lastname: Cras
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Martin
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: Peter Paul
authors.initials: PP
authors.lastname: De Deyn
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D020774:Pick Disease of the Brain / Q000235:genetics* / Q000473:pathology*; D058225:Plaque, Amyloid / Q000235:genetics* / Q000473:pathology; D053764:Presenilin-1
chemical_list: D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1