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A novel presenilin 1 mutation associated with Pick's disease but not β‐amyloid plaques
Author(s) -
Dermaut Bart,
KumarSingh Samir,
Engelborghs Sebastian,
Theuns Jessie,
Rademakers Rosa,
Saerens Jos,
Pickut Barbara A.,
Peeters Karin,
Van Den Broeck Marleen,
Vennekens Krist'l,
Claes Stephen,
Cruts Marc,
Cras Patrick,
Martin JeanJacques,
Van Broeckhoven Christine,
De Deyn Peter Paul
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20083
Subject(s) - tauopathy , frontotemporal dementia , mutation , biology , tau protein , genetics , presenilin , exon , dementia , gene , alzheimer's disease , disease , pathology , neurodegeneration , medicine
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 β‐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.