DETECTING PRION PROTEIN GENE-MUTATIONS BY DENATURING GRADIENT GEL-ELECTROPHORESIS

Mutations of the prion protein (PrP) gene are present in patients with Gerstmann-Straussler-Scheinker syndrome (GSS), familial Creutzfeldt-J akob disease (CJD), and fatal familial insomnia (FFI). We developed a denaturing gradient gel electrophoresis (DGGE) strategy that readily i dentifies point mutations in the PrP coding sequence. By comparison wi th appropriate controls, haplotypes often may be deduced. This method permits samples from many patients with GSS, CJD, as well as patients with unusual degenerative neurologic disorders, to be screened rapidly , sensitively, and inexpensively for the presence of known and novel P rP mutations. We illustrate the sensitivity of this approach by report ing 2 novel polymorphisms in the PrP coding sequence. (C) 1994 Wiley-L iss, Inc.