title: Uncommon polymorphism in the presenilin genes in human familial Alzheimer's disease: not to be mistaken with a pathogenic mutation.
abstract: In this article, we studied the frequency of mutations in the presenilin (PSEN) 1, PSEN2 and amyloid precursor protein genes in a group of patients with late-onset Alzheimer's disease (AD). No pathogenic mutations were found, but a rare non-conservative single-nucleotide polymorphism was detected in the PSEN2 gene (P334R) in a large kindred with familial late-onset AD. No cosegregation was observed in this family. Uncommon polymorphisms can be easily mistaken as a pathogenic mutation when segregation is not analyzed. Family segregation study represents an essential point in considering the pathogenicity of these mutations. These uncommon single-nucleotide polymorphisms should be always taken into account in the genetic testing of AD. They may well have important implications for genetic counselling in AD.
authors.affiliation: Neurology Service, Institut d'Investigacions Biomediques August Pi i Suyner (IDIBAPS), Hospital Clínic, Barcelona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lleó
authors.forename: Magda
authors.initials: M
authors.lastname: Castellví
authors.forename: Rafael
authors.initials: R
authors.lastname: Blesa
authors.forename: Rafael
authors.initials: R
authors.lastname: Oliva
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D001923:Brain Chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000502:physiology*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053764:Presenilin-1; D053766:Presenilin-2
chemical_list: D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2