title: Novel Mutation (Gly212Val) in the PS2 Gene Associated with Early-Onset Familial Alzheimer's Disease.
abstract: Mutations in the presenilin 2 gene (PS2) are an extremely rare cause of early-onset autosomal dominant Alzheimer's disease (AD), accounting for only 5% of these families. These cases represent a particular model of AD, and the scarcity of reports on their clinical phenotypes makes them of great interest. We report a family with early-onset autosomal dominant AD in four members, where the two living siblings were found to carry the novel PS2 mutation Gly212Val (exon 7, transmembrane domain IV) with highly predicted pathogenicity. Age at onset ranged from 60 to 65 years and three of the cases died between ages 74 and 76 years. Clinical phenotype was quite homogeneous among affected members of the family, and overall features, including cognitive decline, tau/p-tau and amyloid-β cerebrospinal fluid markers, neuroimaging, and neuropathology were consistent with typical AD. Lewy bodies were present but restricted to the amygdala.
authors.affiliation: Dementia Care Unit, Virgen de la Arrixaca University Hospital, IMIB (Instituto Murciano de Investigación Biosanitaria), Murcia, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Marín-Muñoz
authors.affiliation: Dementia Care Unit, Virgen de la Arrixaca University Hospital, IMIB (Instituto Murciano de Investigación Biosanitaria), Murcia, Spain.
authors.forename: Ma Fuensanta
authors.initials: MF
authors.lastname: Noguera-Perea
authors.affiliation: Department of Neurology, Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Estrella
authors.initials: E
authors.lastname: Gómez-Tortosa
authors.affiliation: Murcia Brain Bank, Murcia, Spain.
authors.forename: David
authors.initials: D
authors.lastname: López-Motos
authors.affiliation: Dementia Care Unit, Virgen de la Arrixaca University Hospital, IMIB (Instituto Murciano de Investigación Biosanitaria), Murcia, Spain.
authors.forename: Martirio
authors.initials: M
authors.lastname: Antequera-Torres
authors.affiliation: Dementia Care Unit, Virgen de la Arrixaca University Hospital, IMIB (Instituto Murciano de Investigación Biosanitaria), Murcia, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Martínez-Herrada
authors.affiliation: Dementia Care Unit, Virgen de la Arrixaca University Hospital, IMIB (Instituto Murciano de Investigación Biosanitaria), Murcia, Spain.
authors.forename: Salvadora
authors.initials: S
authors.lastname: Manzanares-Sánchez
authors.affiliation: Dementia Care Unit, Virgen de la Arrixaca University Hospital, IMIB (Instituto Murciano de Investigación Biosanitaria), Murcia, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Vivancos-Moreau
authors.affiliation: Dementia Care Unit, Virgen de la Arrixaca University Hospital, IMIB (Instituto Murciano de Investigación Biosanitaria), Murcia, Spain.
authors.forename: Agustina
authors.initials: A
authors.lastname: Legaz-García
authors.affiliation: Department of Neuropathology and Brain Tissue Bank, Fundación CIEN, Carlos III Health Institute, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Rábano-Gutiérrez Del Arroyo
authors.affiliation: Dementia Care Unit, Virgen de la Arrixaca University Hospital, IMIB (Instituto Murciano de Investigación Biosanitaria), Murcia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Antúnez-Almagro
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005998:Glycine / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053766:Presenilin-2 / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D014633:Valine / Q000235:genetics
chemical_list: C508861:PSEN2 protein, human; D053766:Presenilin-2; D014633:Valine; D005998:Glycine
keywords: Early-onset dementia; familial Alzheimer’s disease; neurogenetics; presenilin 2 mutation