A MUTATION IN CODON-717 OF THE AMYLOID PRECURSOR PROTEIN GENE IN AN AUSTRALIAN FAMILY WITH ALZHEIMERS-DISEASE

DNA from the probands of seven Australian families with hereditary Alz heimer's disease was screened for the presence of known mutations in t he amyloid precursor protein (APP) gene on chromosome 21 using single stranded conformational polymorphism (SSCP) analysis [14]. One subject was found to have a mutation causing a Val --> tie substitution at po sition 717. This was confirmed by restriction enzyme digestion and seq uencing. The mutation has been found in both the other affected family members available for study and in two at-risk relatives. It was not present in the only living unaffected relative who has passed the usua l age of onset in this family. There is so far no evidence that apolip oprotein E (APOE) genotype influences age of onset in this family, tho ugh numbers are small. Two other families with autopsy confirmation an d age of onset in the fifth decade had no APP mutation and are thought likely to have a mutation on chromosome 14 on the basis of their earl ier onset age.