title: PEN-2 gene mutation in a familial Alzheimer's disease case.
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.
authors.affiliation: Istituto di Ricerche Farmacologiche "Mario Negri", Via Eritrea 62, 20157, Milano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Sala Frigerio
authors.forename: P
authors.initials: P
authors.lastname: Piscopo
authors.forename: E
authors.initials: E
authors.lastname: Calabrese
authors.forename: A
authors.initials: A
authors.lastname: Crestini
authors.forename: L
authors.initials: L
authors.lastname: Malvezzi Campeggi
authors.forename: R
authors.initials: R
authors.lastname: Civita di Fava
authors.forename: S
authors.initials: S
authors.lastname: Fogliarino
authors.forename: D
authors.initials: D
authors.lastname: Albani
authors.forename: G
authors.initials: G
authors.lastname: Marcon
authors.forename: R
authors.initials: R
authors.lastname: Cherchi
authors.forename: R
authors.initials: R
authors.lastname: Piras
authors.forename: G
authors.initials: G
authors.lastname: Forloni
authors.forename: A
authors.initials: A
authors.lastname: Confaloni
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases; D001483:Base Sequence; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D008565:Membrane Proteins; C469349:PSENEN protein, human; D053829:Amyloid Precursor Protein Secretases