title: Identification of a novel mutation (Leu282Arg) of the human presenilin 1 gene in Alzheimer's disease.
abstract: Many different mutations, causative of Alzheimer's disease, have been found in the presenilin-1 gene (PS-1). We have developed a screening method based on denaturing gradient gel electrophoresis (DGGE), which allows the mutational analysis of the whole exon 9 of PS-1. Upon the screening of a Spanish sample of early onset familial Alzheimer disease cases, we have found a novel mutation in the PS-1 gene. The mutation (a T to G transition) results in a change of the amino acid at position 282 of the presenilin protein from leucine to arginine. This mutation is located in the hydrophobic domain number 7 (exon 9) close to the site of physiological cleavage processing. The average of onset of the affected members of this family is 43+/-5 years, and the average age of exitus of affected members is 56+/-3 years. The possibility to determine the specific pathologic mechanisms of this mutation is now open.
authors.affiliation: Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Aldudo
authors.forename: M J
authors.initials: MJ
authors.lastname: Bullido
authors.forename: T
authors.initials: T
authors.lastname: Arbizu
authors.forename: R
authors.initials: R
authors.lastname: Oliva
authors.forename: F
authors.initials: F
authors.lastname: Valdivieso
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics*; D019943:Amino Acid Substitution / Q000235:genetics*; D001120:Arginine / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007930:Leucine / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic; D053764:Presenilin-1; D012307:Risk Factors
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D001120:Arginine; D007930:Leucine