1. PEN-2 gene mutation in a familial Alzheimer's disease case.
- Author
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Sala Frigerio C, Piscopo P, Calabrese E, Crestini A, Malvezzi Campeggi L, Civita di Fava R, Fogliarino S, Albani D, Marcon G, Cherchi R, Piras R, Forloni G, and Confaloni A
- Subjects
- Aged, Amyloid Precursor Protein Secretases, Base Sequence, Blotting, Western, Chromatography, High Pressure Liquid, Female, Humans, Male, Pedigree, Polymorphism, Genetic, Reverse Transcriptase Polymerase Chain Reaction, Alzheimer Disease genetics, Genetic Predisposition to Disease, Membrane Proteins genetics, Mutation
- Abstract
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.
- Published
- 2005
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