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 Lugaresi; Pierluigi Gambetti

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 journal › Article › peer-review

620 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, 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.

Original language	English
Pages (from-to)	806-808
Number of pages	3
Journal	Science
Volume	258
Issue number	5083
State	Published - Oct 30 1992

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Goldfarb, L. G., Petersen, R. B., Tabaton, M., Brown, P., LeBlanc, A. C., Montagna, P., Cortelli, P., Julien, J., Vital, C., Pendelbury, W. W., Haltia, M., Wills, P. R., Hauw, J. J., McKeever, P. E., Monari, L., Schrank, B., Swergold, G. D., Autilio-Gambetti, L., Gajdusek, D. C., ... Gambetti, P. (1992). Fatal familial insomnia and familial Creutzfeldt-Jakob disease: Disease phenotype determined by a DNA polymorphism. Science, 258(5083), 806-808.

@article{4d1ffc0343614173b028c18f389415d4,

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.",

author = "Goldfarb, {Lev G.} and Petersen, {Robert B.} and Massimo Tabaton and Paul Brown and LeBlanc, {Andr{\'e}a C.} and Pasquale Montagna and Pietro Cortelli and Jean Julien and Claude Vital and Pendelbury, {William W.} and Matti Haltia and Wills, {Peter R.} and Hauw, {Jean J.} and McKeever, {Paul E.} and Lucia Monari and Bertold Schrank and Swergold, {Gary D.} and Lucila Autilio-Gambetti and Gajdusek, {D. Carleton} and Elio Lugaresi and Pierluigi Gambetti",

year = "1992",

month = oct,

day = "30",

language = "English",

volume = "258",

pages = "806--808",

journal = "Science",

issn = "0036-8075",

publisher = "Science",

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Goldfarb, LG, Petersen, RB, Tabaton, M, Brown, P, LeBlanc, AC, Montagna, P, Cortelli, P, Julien, J, Vital, C, Pendelbury, WW, Haltia, M, Wills, PR, Hauw, JJ, McKeever, PE, Monari, L, Schrank, B, Swergold, GD, Autilio-Gambetti, L, Gajdusek, DC, Lugaresi, E & Gambetti, P 1992, 'Fatal familial insomnia and familial Creutzfeldt-Jakob disease: Disease phenotype determined by a DNA polymorphism', Science, vol. 258, no. 5083, pp. 806-808.

TY - JOUR

T1 - Fatal familial insomnia and familial Creutzfeldt-Jakob disease

T2 - Disease phenotype determined by a DNA polymorphism

AU - Goldfarb, Lev G.

AU - Petersen, Robert B.

AU - Tabaton, Massimo

AU - Brown, Paul

AU - LeBlanc, Andréa C.

AU - Montagna, Pasquale

AU - Cortelli, Pietro

AU - Julien, Jean

AU - Vital, Claude

AU - Pendelbury, William W.

AU - Haltia, Matti

AU - Wills, Peter R.

AU - Hauw, Jean J.

AU - McKeever, Paul E.

AU - Monari, Lucia

AU - Schrank, Bertold

AU - Swergold, Gary D.

AU - Autilio-Gambetti, Lucila

AU - Gajdusek, D. Carleton

AU - Lugaresi, Elio

AU - Gambetti, Pierluigi

PY - 1992/10/30

Y1 - 1992/10/30

N2 - 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.

AB - 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.

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M3 - Article

C2 - 1439789

AN - SCOPUS:0026496257

SN - 0036-8075

VL - 258

SP - 806

EP - 808

JO - Science

JF - Science

IS - 5083

ER -

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

Abstract

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