• Andrea Tedde, Benedetta Nacmias, Monica Ciantelli, Paolo Forleo, Elena Cellini, Silvia Bagnoli, Carolina Piccini, Paolo Caffarra, Enrico Ghidoni, Marco Paganini, Laura Bracco, and Sandro Sorbi.
• Department of Neurological and Psychiatric Sciences, University of Florence, Italy.
• Arch Neurol Chicago. 2003 Nov 1;60(11):1541-4.

BackgroundMutations in the presenilin 1 (PS1) and presenilin 2 (PS2) genes, and more rarely in beta-amyloid precursor protein (betaAPP), underlie the pathogenesis of most cases of familial Alzheimer disease (FAD).ObjectiveTo screen the entire coding region of the PS1 and PS2 genes and exons 16 and 17 of the betaAPP to find pathogenetic mutations in FAD. Patients Patients with FAD were consecutively enrolled from among the outpatients from the neurology departments at the Universities of Florence and Parma and the Santa Maria Nuova Hospital in Reggio Emilia, Italy.Design And MethodsPolymerase chain reaction-single-strand conformation polymorphism and DNA se-quencing were used to investigate the affected members of families with FAD.ResultsWe identified a family carrying a novel Ser130Leu mutation in the PS2 gene. Moreover, we found 2 novel PS1 mutations: Cys92Ser in exon 4 in 2 unrelated families and Leu174Met in exon 6 in the PS1 gene. We also found a fourth Italian family with the betaAPP Val717Ile mutation.ConclusionsOne novel PS2 mutation associated with highly penetrant but variable age at onset (35-85 years) and 2 novel PS1 missense mutations associated with early-onset Alzheimer disease at age 49 to 54 years have been identified in Italian families. Screening for new mutations in presenilin and betaAPP genes was beneficial in characterizing gene function in FAD.

23 keywords...

hide…