A novel presenilin 1 mutation associated with Pick's disease but not beta-amyloid plaques.
Ann Neurol
; 55(5): 617-26, 2004 May.
Article
in En
| MEDLINE
| ID: mdl-15122701
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Amyloid beta-Peptides
/
Plaque, Amyloid
/
Pick Disease of the Brain
/
Membrane Proteins
/
Mutation
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Ann Neurol
Year:
2004
Document type:
Article
Affiliation country: