title: A novel pathogenic PSEN1 mutation in a family with Alzheimer's disease: phenotypical and neuropathological features.
abstract: We report a novel presenilin1 (PSEN1) gene mutation (I143 V) in a four-generation family with Alzheimer's disease. Clinical, molecular, and neuropathological examinations were performed on index patient; thirteen affected subjects were also identified. The index patient presented at 55 with personality changes, apathy, reduction of verbal fluency, and temporal and spatial disorientation. At 68, she showed visual hallucinations; blurred language, and rigidity. She became bedridden and died at 75. A novel mutation at codon 143 was found in PSEN1 gene, changing isoleucine to valine. The brain showed severe atrophy of the frontal and temporal lobes. Parenchymal amyloid-β (Aβ) deposits were abundant, diffuse to grey structures and contained Aβ42, but very few Aβ40. Amyloid angiopathy was absent. Neurofibrillary changes were severe. Our study confirms that PSEN1 mutations can be associated with unusual phenotypes. The peculiarity of the age at onset (not very early), the long course, and the frontal involvement, together with the rather complete absence of Aβ40 and of amyloid angiopathy, widen the spectrum of PSEN1-linked phenotypes.
authors.affiliation: Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia Terme (CZ), Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Gallo
authors.forename: Norina
authors.initials: N
authors.lastname: Marcello
authors.forename: Sabrina A M
authors.initials: SA
authors.lastname: Curcio
authors.forename: Rosanna
authors.initials: R
authors.lastname: Colao
authors.forename: Silvana
authors.initials: S
authors.lastname: Geracitano
authors.forename: Livia
authors.initials: L
authors.lastname: Bernardi
authors.forename: Maria
authors.initials: M
authors.lastname: Anfossi
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Puccio
authors.forename: Francesca
authors.initials: F
authors.lastname: Frangipane
authors.forename: Alessandra
authors.initials: A
authors.lastname: Clodomiro
authors.forename: Maria
authors.initials: M
authors.lastname: Mirabelli
authors.forename: Franca
authors.initials: F
authors.lastname: Vasso
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Smirne
authors.forename: Gabriella
authors.initials: G
authors.lastname: Muraca
authors.forename: Raffaele
authors.initials: R
authors.lastname: Di Lorenzo
authors.forename: Raffaele
authors.initials: R
authors.lastname: Maletta
authors.forename: Enrico
authors.initials: E
authors.lastname: Ghidoni
authors.forename: Orso
authors.initials: O
authors.lastname: Bugiani
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giaccone
authors.forename: Amalia C
authors.initials: AC
authors.lastname: Bruni
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D053764:Presenilin-1 / Q000235:genetics*; D014633:Valine / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; C508853:PSEN1 protein, human; D053764:Presenilin-1; D007532:Isoleucine; D014633:Valine