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Presenilin enhancer‐2 gene: Identification of a novel promoter mutation in a patient with early‐onset familial Alzheimer's disease
Author(s) -
Andreoli Virginia,
Trecroci Francesca,
La Russa Antonella,
Cittadella Rita,
Liguori Maria,
Spadafora Patrizia,
Caracciolo Manuela,
Di Palma Gemma,
Colica Carmela,
Gambardella Antonio,
Quattrone Aldo
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.02.010
Subject(s) - presenilin , amyloid precursor protein , enhancer , genetics , gene , biology , mutant , nicastrin , alzheimer's disease , mutation , exon , promoter , allele , disease , medicine , transcription factor , gene expression , pathology
γ‐Secretase proteins complex cleaves the amyloid precursor protein (APP) to generate amyloid‐β (Aβ) peptides. Considerable evidence suggests that alterations in genes encoding these proteins exert their influence on the pathogenesis of familial Alzheimer's disease (FAD). Presenilin enhancer‐2 gene ( PEN‐2 ) is a necessary component of the γ‐Secretase complex. Recently, it has been shown that PEN‐2 mutations could be involved in Alzheimer's disease (AD). We performed a mutational screening of all PEN‐2 coding and promoter regions in a FAD cohort derived from Southern Italy. Four hundred and fifty‐two subjects (FAD: 97; Controls: 355) were recruited for this study. 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. 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.