Marín-Muñoz Juan, Noguera-Perea Ma Fuensanta, Gómez-Tortosa Estrella, López-Motos David, Antequera-Torres Martirio, Martínez-Herrada Begoña, Manzanares-Sánchez Salvadora, Vivancos-Moreau Laura, Legaz-García Agustina, Rábano-Gutiérrez Del Arroyo Alberto, Antúnez-Almagro Carmen
Dementia Care Unit, Virgen de la Arrixaca University Hospital, IMIB (Instituto Murciano de Investigación Biosanitaria), Murcia, Spain.
Department of Neurology, Fundación Jiménez Díaz, Madrid, Spain.
J Alzheimers Dis. 2016 Apr 25;53(1):73-8. doi: 10.3233/JAD-160050.
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.
