Presenilin enhancer-2 gene: Identification of a novel promoter mutation in a patient with early-onset familial Alzheimer's disease

Background: g-Secretase proteins complex cleaves the amyloid precursor protein (APP) to generate amyloid -b (Ab) peptides. Considerable evidence suggests that alterations in genes encoding these proteins exert their influence on the pathogenesis of familial Alzheimer disease (FAD). Presenilin enhancer-2 gene (PEN-2) is a necessary component of the g-Secretase complex. Recently it has been shown that PEN-2 mutations could be involved in Alzheimer's disease (AD). Methods: We performed a mutational screening of all PEN-2 coding and promoter regions in a FAD cohort derived from Southern Italy . 452 subjects (FAD: 97; Controls: 355) were recruited for this study. Results: We identified for the first time in a key region necessary for the promoter activity a novel 3 bp deletion in a subject with early-FAD. Our genetic data demonstrate that the mutant allele may influence the transcriptional activity of the PEN-2 gene. Conclusions: Although the effective role of the PEN-2 promoter deletion in AD is not entirely clear, these findings might lead to more studies on its functional and genetic role.