A novel presenilin 1 mutation associated with Pick's disease but not beta-amyloid plaques
Dermaut, Bart Kumar-Singh, S Engelborghs, S Theuns, J Rademakers, R Sacrens, J Pickut, BA Peeters, K van den Broeck, M Vennekens, K Claes, Stephan Cruts, M Cras, P Martin, JJ Van Broeckhoven, C De Deyn, PP #
Annals of neurology vol:55 issue:5 pages:617-626
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 I (PSI) mutations (Leu113Pro and insArg352) recently have been associated with familial FTD albeit without neuropathological confirmation. We report here a novel PSI 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 PSI as a candidate gene for Pick-type tauopathy without MAPT mutations.