title: Novel presenilin 1 mutation (Ile408Thr) in an Italian family with late-onset Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a neurodegenerative disease affecting over 20 million people worldwide, mainly adult subjects in advanced age. Over 240 different fully penetrant autosomal dominant mutations in 532 families around the world have been described in three genes [i.e., amyloid precursor protein (APP), and presenilins (PSEN1 and PSEN2)] causing 50% of all Familial AD. We report a new mutation (p.Ile408Thr, c. 1223T>C) in the PSEN1 gene in one autosomal dominant Late Onset AD patient. The genetic variation occurred in a conserved domain of the protein and was present in the proband and in the younger sister who is likely to be prodromal AD. Thus, we suggest that this variant will have probably a pathogenic effect, hypothesizing a possible key role of this new mutation in the pathogenesis of Alzheimer's disease for this family.
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tedde
authors.affiliation: Villa Serena Hospital, Città S. Angelo, Pescara, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Bartoli
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Piaceri
authors.affiliation: Villa Serena Hospital, Città S. Angelo, Pescara, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Ferrara
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bagnoli
authors.affiliation: Villa Serena Hospital, Città S. Angelo, Pescara, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Serio
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Sorbi
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Italy. Electronic address: nacmias@unifi.it.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Nacmias
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation; D010375:Pedigree; D053764:Presenilin-1 / Q000235:genetics*
chemical_list: C508853:PSEN1 protein, human; D053764:Presenilin-1
keywords: APP; Alzheimer’s disease; DNA; PSEN1; PSEN2