Mutations in familial Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker's syndrome.

A host protein encoded by the gene specifying the scrapie amyloid precursor affects pathogenesis of the transmissible spongiform encephalopathies: Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker's syndrome (GSS), and kuru in man, and scrapie in animals. We found a mutation in this gene of two patients with CJD from one family and a second mutation in the same gene in three patients with GSS from another family. The mutation in two related familial CJD patients changed glutamine in position 200 tolysine. This mutation was absent in other individuals including unrelated patients with familial CJD, sporadic CJD, and GSS. The other mutation in three GSS patients changed proline in position 102 to leucine, the same mutation described recently in some GSS families. We did not find it in six unaffected relatives of the GSS patients or in other individuals including sporadic and familial CJD patients. A rare insertion described earlier in one CJD family was also absent in all tested individuals.