Fatal familial insomnia and familial Creutzfeldt-Jakob disease: Disease phenotype determined by a DNA polymorphism

Lev G. Goldfarb, Robert B. Petersen, Massimo Tabaton, Paul Brown, Andréa C. LeBlanc, Pasquale Montagna, Pietro Cortelli, Jean Julien, Claude Vital, William W. Pendelbury, Matti Haltia, Peter R. Wills, Jean J. Hauw, Paul E. McKeever, Lucia Monari, Bertold Schrank, Gary D. Swergold, Lucila Autilio-Gambetti, D. Carleton Gajdusek, Elio LugaresiPierluigi Gambetti

Research output: Contribution to journalArticlepeer-review

595 Scopus citations

Abstract

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, Asn 178 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.

Original languageEnglish
Pages (from-to)806-808
Number of pages3
JournalScience
Volume258
Issue number5083
DOIs
StatePublished - 1992

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