FAMILIAL CREUTZFELDT-JAKOB-DISEASE WITH A 5-REPEAT OCTAPEPTIDE INSERTMUTATION

We report a familial form of Creutzfeldt-Jakob disease, associated wit h a unique insert mutation of the PRNP gene in an American family of U krainian origin. Ten family members exhibited early age at onset and l ong-duration illnesses characterized primarily by personality changes, cognitive impairment, and spasticity. The proband, presenting at age 42 years, exhibited a fairly stable, nonprogressive course over 7 year s, followed by precipitous decline and death in the eighth year. Other affected family members exhibited marked clinical heterogeneity. Each tested affected member had an insert mutation consisting of five extr a octapeptide repeats between codons 51 and 91 of the PRNP gene on chr omosome 20. Examination of two autopsy cases showed classic spongiform change, neuronal loss and astrocytosis in one case, and minimal patho logic abnormality in the other case. This report documents a new inser t mutation of the PRNP gene, and confirms the early age of onset, char acteristically prolonged clinical course, and clinical and pathologic heterogeneity seen in such mutations.