rs74315401

This study presents a comprehensive analysis of PRNP gene mutations from 19 years of diagnostic sequencing of 3,664 samples at the MRC Prion Unit. The authors identified 14 pathogenic missense mutations and several octapeptide repeat insertions/deletions, including novel variants (G54S, D167N, V209M, Q212PP) and rare mutations (P105L, G114V) with detailed clinical phenotypes. Population screening of 1,007 healthy controls from 51 diverse populations revealed codon 129 polymorphism frequencies and confirmed several variants (G54S, G142S, N171S) as non-pathogenic polymorphisms, while absence from all tested populations supports pathogenicity of G114V and D167N.

This PhD thesis examines host range and strain characteristics of chronic wasting disease (CWD) in cervids through experimental transmission to Syrian Golden hamsters. The study demonstrates that CWD isolates from deer with different prion protein (PrP) genotypes (wild-type, H95, S96) exhibit variable infectivity in hamsters and mice, with PrP polymorphisms at codons 95 and 96 affecting host range. The H95 variant produces a novel strain (H95+) with altered transmission properties compared to the parent Wisc-1 strain, indicating CWD strain diversity correlates with cervid species, geographic location, and PrP genotype.

This study identified a missense variant in the prion protein gene (PRNP) at codon 102 (Pro→Leu, Leu102) in Japanese patients with Creutzfeldt-Jakob disease (CJD) with congophilic kuru plaques. This variant, previously associated with Gerstmann-Straussler syndrome (GSS), was found heterozygously in 6 of 7 CJD-KP patients but absent in 8 CJD patients without kuru plaques, suggesting CJD-KP should be classified as GSS rather than CJD. The variant was also detected in unaffected family members of affected patients.