A novel presenilin 1 mutation associated with Pick's disease but not beta-amyloid plaques.
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.
Dermaut
Bart
B
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium.
Kumar-Singh
Samir
S
Engelborghs
Sebastian
S
Theuns
Jessie
J
Rademakers
Rosa
R
Saerens
Jos
J
Pickut
Barbara A
BA
Peeters
Karin
K
van den Broeck
Marleen
M
Vennekens
Krist'l
K
Claes
Stephen
S
Cruts
Marc
M
Cras
Patrick
P
Martin
Jean-Jacques
JJ
Van Broeckhoven
Christine
C
De Deyn
Peter Paul
PP
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
D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1