First report of polymorphisms in the prion-like protein gene (PRND): implications for human prion diseases.

The aim of this study was to investigate the possible involvement of genetic variation in the prion-like protein gene (PRND), which encodes the doppel protein (Dpl), in the aetiology of human prion diseases. Patients with sporadic, infectious or genetic forms of human prion diseases and controls were systematically screened, using the single-strand conformational polymorphism method, for genetic variants of the PRND gene. Four polymorphisms in PRND (three structural changes, T26M, P56L and T174M and a silent polymorphism, T(174)T) were detected. No strong association was found between any of these polymorphisms and human prion diseases but certain PRND alleles may be useful markers for tracing the chromosomal ancestry of PRNP mutations. Although genetic variation in PRND does not seem to play a major role in the pathogenesis of prion diseases, this first report of PRND polymorphisms may open up new possibilities for investigating the involvement of such polymorphisms in other human diseases.