PEN-2 gene mutation in a familial Alzheimer's disease case

Genetic evidence indicates a central role of cerebral accumulation of beta-amyloid (Abeta) in the pathogenesis of Alzheimer's disease (AD). Beside presenilin 1 and 2, three other recently discovered proteins (Aph 1, PEN 2 and nicastrin) are associated with gamma-secretase activity, the enzymati...

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Bibliographic Details
Published in:Journal of neurology 2005-09, Vol.252 (9), p.1033-1036
Main Authors: FRIGERIO, Carlo Sala, PISCOPO, Paola, PIRAS, Rita, FORLONI, Gianluigi, CONFALONI, Annamaria, CALABRESE, Elena, CRESTINI, Alessio, MALVEZZI, Lorenzo, DI FAVA, Campeggi Rita, FOGLIARINO, Sergio, ALBANI, Diego, MARCON, Gabriella, CHERCHI, Rosella
Format: Article
Language:English
Subjects:
Aged
Alzheimer Disease - genetics
Amyloid Precursor Protein Secretases
Base Sequence
Biological and medical sciences
Blotting, Western
Chromatography, High Pressure Liquid
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Female
Genetic Predisposition to Disease
Humans
Male
Medical sciences
Membrane Proteins - genetics
Mutation
Neurology
Pedigree
Polymorphism, Genetic
Reverse Transcriptase Polymerase Chain Reaction
Tumors of the nervous system. Phacomatoses
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Summary:Genetic evidence indicates a central role of cerebral accumulation of beta-amyloid (Abeta) in the pathogenesis of Alzheimer's disease (AD). Beside presenilin 1 and 2, three other recently discovered proteins (Aph 1, PEN 2 and nicastrin) are associated with gamma-secretase activity, the enzymatic complex generating Abeta. Alterations in genes encoding these proteins were candidates for a role in AD. The PEN 2 gene was examined for unknown mutations and polymorphisms in sporadic and familial Alzheimer patients. Samples from age-matched controls (n=253), sporadic AD (SAD, n=256) and familial AD (FAD, n=140) were screened with DHPLC methodology followed by sequencing. Scanning the gene identified for the first time a missense mutation (D90N) in a patient with FAD. Three intronic polymorphisms were also identified, one of which had a higher presence of the mutated allele in AD subjects carrying the allele epsilon4 of apolipoprotein E than controls. The pathogenic role of the PEN-2 D90N mutation in AD is not clear, but the findings might lead to new studies on its functional and genetic role.
ISSN:0340-5354
1432-1459
DOI:10.1007/s00415-005-0799-7