title: Presenilin enhancer-2 gene: identification of a novel promoter mutation in a patient with early-onset familial Alzheimer's disease.
abstract: 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;
  
  
  METHODS
  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.
authors: Institute of Neurological Sciences, National Research Council, Pianolago di Mangone, Cosenza, Italy. v.andreoli@isn.cnr.it
authors: Virginia
authors: V
authors: Andreoli
authors: Francesca
authors: F
authors: Trecroci
authors: Antonella
authors: A
authors: La Russa
authors: Rita
authors: R
authors: Cittadella
authors: Maria
authors: M
authors: Liguori
authors: Patrizia
authors: P
authors: Spadafora
authors: Manuela
authors: M
authors: Caracciolo
authors: Gemma
authors: G
authors: Di Palma
authors: Carmela
authors: C
authors: Colica
authors: Antonio
authors: A
authors: Gambardella
authors: Aldo
authors: A
authors: Quattrone
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C469349:PSENEN protein, human; D053829:Amyloid Precursor Protein Secretases