IDENTIFICATION OF A NOVEL MUTATION (LEU282ARG) OF THE HUMAN PRESENILIN-1 GENE IN ALZHEIMERS-DISEASE

Many different mutations, causative of Alzheimer's disease, have been found in the presenilin-1 gene (PS-1). We have developed a screening m ethod based on denaturing gradient gel electrophoresis (DGGE), which a llows the mutational analysis of the whole exon 9 ai PS-l. Upon the sc reening 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 s ite 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 d etermine the specific pathologic mechanisms of this mutation is now op en. (C) 1998 Published by Elsevier Science Ireland Ltd.