Fatal Familial Insomnia and Familial Creutzfeldt-Jakob Disease: Disease Phenotype Determined by a DNA Polymorphism

作者：Lev G. Goldfarb, Robert B. Petersen, Massimo Tabaton, Paul Brown, Andrea Claire LeBlanc, Pasquale Montagna, Pietro Cortelli, Jean Julien, Claude Vital, William W. Pendelbury, M Haltia, Peter R. Wills, J.J. Hauw, Paul E. McKeever, Lucia Monari, Bertold Schrank, Gary D. Swergold, LUCILA AUTILIO‐GAMBETTI, D. Carleton Gajdusek, Elio Lugaresi, Pierluigi L. Gambetti · 发表于：Science · 年份：1992 · DOI：10.1126/science.1439789 · 被引用次数：725 · 研究领域：Prion Diseases and Protein Misfolding、Amyotrophic Lateral Sclerosis Research、Trace Elements in Health

Fatal familial insomnia (FFI) and a subtype of familial Creutzfeldt-Jakob disease (CJD), two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asn178) of the prion protein gene. The possibility that a second genetic component modified the phenotypic expression of the Asn178 mutation was investigated. FFI and the familial CJD subtype segregated with different genotypes determined by the Asn178 mutation and the methionine-valine polymorphism at codon 129. The Met129, Asn178 allele segregated with FFI in all 15 affected members of five kindreds whereas the Val129, Asn178 allele segregated with the familial CJD subtype in all 15 affected members of six kindreds. Thus, two distinct disease phenotypes linked to a single pathogenic mutation can be determined by a common polymorphism.