title: Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism.
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, 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.
authors.affiliation: Laboratory of Central Nervous System Studies, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: L G
authors.initials: LG
authors.lastname: Goldfarb
authors.forename: R B
authors.initials: RB
authors.lastname: Petersen
authors.forename: M
authors.initials: M
authors.lastname: Tabaton
authors.forename: P
authors.initials: P
authors.lastname: Brown
authors.forename: A C
authors.initials: AC
authors.lastname: LeBlanc
authors.forename: P
authors.initials: P
authors.lastname: Montagna
authors.forename: P
authors.initials: P
authors.lastname: Cortelli
authors.forename: J
authors.initials: J
authors.lastname: Julien
authors.forename: C
authors.initials: C
authors.lastname: Vital
authors.forename: W W
authors.initials: WW
authors.lastname: Pendelbury
mesh_terms: D000328:Adult; D001216:Asparagine / Q000235:genetics; D002890:Chromosomes, Human, Pair 20; D003062:Codon; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D017096:Prion Diseases / Q000235:genetics*; D011328:Prions / Q000235:genetics; D014633:Valine / Q000235:genetics
chemical_list: D003062:Codon; D011328:Prions; D001216:Asparagine; D004247:DNA; D014633:Valine