A NOVEL PATHOGENIC MUTATION (LEU262PHE) FOUND IN THE PRESENILIN-1 GENE IN EARLY-ONSET ALZHEIMERS-DISEASE

Several mutations causing early-onset familial Alzheimer's disease (AD ) have been detected in the presenilin 1 (PS-1) gene. Pathogenic mutat ions have also been described in an homologous gene, presenilin 2 (PS- 2). In order to screen for mutations in these genes, cDNA samples from early-onset AD cases were analysed, using single strand conformation polymorphism (SSCP) and direct cDNA sequencing. Two missense mutations in the PS-I gene were detected, a previously unidentified amino acid substitution Leu262Phe and an earlier reported amino acid substitution Glu318Gly. No disease-related mutations were found in the PS-2 gene. (C) 1997 Elsevier Science Ireland Ltd.