Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene

P. Brown, L. G. Goldfarb, W. R. McCombie, A. Nieto, D. Squillacote, William Sheremata, B. W. Little, M. S. Godec, C. J. Gibbs, D. C. Gajdusek

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

An American family of English origin with an unusually early onset and long-duration form of Creutzfeldt-Jakob disease (CJD) had a heterozygous insert mutation in the region of repeating octapeptide coding sequences between codons 51 and 91 of the PRNP gene on chromosome 20. Affected members were 23 to 35 years old at the onset of illnesses that lasted from 4 to 13 years, yet experimental transmission of disease from the proband (11-year duration) produced a typically brief incubation period and duration of illness in each of three inoculated primates. Also, the PrP amyloid protein that accumulates in CJD brain was only barely detectable in extracted brain tissue from one case with massive spongiform change and was undetectable in another case with no spongiform change, perhaps because of epitope shielding by a configurational change in the protein induced by the mutation. Analysis of this and other families with similar inserts suggests that such mutations in the PRNP gene not only predispose to CJD, but also modify its phenotypic expression.

Original languageEnglish
Pages (from-to)422-427
Number of pages6
JournalNeurology
Volume42
Issue number2
StatePublished - Feb 1 1992

Fingerprint

Creutzfeldt-Jakob Syndrome
Amyloid
Mutation
Chromosomes, Human, Pair 20
Genes
Amyloidogenic Proteins
Brain
Codon
Primates
Epitopes
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Brown, P., Goldfarb, L. G., McCombie, W. R., Nieto, A., Squillacote, D., Sheremata, W., ... Gajdusek, D. C. (1992). Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene. Neurology, 42(2), 422-427.

Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene. / Brown, P.; Goldfarb, L. G.; McCombie, W. R.; Nieto, A.; Squillacote, D.; Sheremata, William; Little, B. W.; Godec, M. S.; Gibbs, C. J.; Gajdusek, D. C.

In: Neurology, Vol. 42, No. 2, 01.02.1992, p. 422-427.

Research output: Contribution to journalArticle

Brown, P, Goldfarb, LG, McCombie, WR, Nieto, A, Squillacote, D, Sheremata, W, Little, BW, Godec, MS, Gibbs, CJ & Gajdusek, DC 1992, 'Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene', Neurology, vol. 42, no. 2, pp. 422-427.
Brown P, Goldfarb LG, McCombie WR, Nieto A, Squillacote D, Sheremata W et al. Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene. Neurology. 1992 Feb 1;42(2):422-427.
Brown, P. ; Goldfarb, L. G. ; McCombie, W. R. ; Nieto, A. ; Squillacote, D. ; Sheremata, William ; Little, B. W. ; Godec, M. S. ; Gibbs, C. J. ; Gajdusek, D. C. / Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene. In: Neurology. 1992 ; Vol. 42, No. 2. pp. 422-427.
@article{5b87a6986f284bebbfa5e3f1f4fd9ced,
title = "Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene",
abstract = "An American family of English origin with an unusually early onset and long-duration form of Creutzfeldt-Jakob disease (CJD) had a heterozygous insert mutation in the region of repeating octapeptide coding sequences between codons 51 and 91 of the PRNP gene on chromosome 20. Affected members were 23 to 35 years old at the onset of illnesses that lasted from 4 to 13 years, yet experimental transmission of disease from the proband (11-year duration) produced a typically brief incubation period and duration of illness in each of three inoculated primates. Also, the PrP amyloid protein that accumulates in CJD brain was only barely detectable in extracted brain tissue from one case with massive spongiform change and was undetectable in another case with no spongiform change, perhaps because of epitope shielding by a configurational change in the protein induced by the mutation. Analysis of this and other families with similar inserts suggests that such mutations in the PRNP gene not only predispose to CJD, but also modify its phenotypic expression.",
author = "P. Brown and Goldfarb, {L. G.} and McCombie, {W. R.} and A. Nieto and D. Squillacote and William Sheremata and Little, {B. W.} and Godec, {M. S.} and Gibbs, {C. J.} and Gajdusek, {D. C.}",
year = "1992",
month = "2",
day = "1",
language = "English",
volume = "42",
pages = "422--427",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene

AU - Brown, P.

AU - Goldfarb, L. G.

AU - McCombie, W. R.

AU - Nieto, A.

AU - Squillacote, D.

AU - Sheremata, William

AU - Little, B. W.

AU - Godec, M. S.

AU - Gibbs, C. J.

AU - Gajdusek, D. C.

PY - 1992/2/1

Y1 - 1992/2/1

N2 - An American family of English origin with an unusually early onset and long-duration form of Creutzfeldt-Jakob disease (CJD) had a heterozygous insert mutation in the region of repeating octapeptide coding sequences between codons 51 and 91 of the PRNP gene on chromosome 20. Affected members were 23 to 35 years old at the onset of illnesses that lasted from 4 to 13 years, yet experimental transmission of disease from the proband (11-year duration) produced a typically brief incubation period and duration of illness in each of three inoculated primates. Also, the PrP amyloid protein that accumulates in CJD brain was only barely detectable in extracted brain tissue from one case with massive spongiform change and was undetectable in another case with no spongiform change, perhaps because of epitope shielding by a configurational change in the protein induced by the mutation. Analysis of this and other families with similar inserts suggests that such mutations in the PRNP gene not only predispose to CJD, but also modify its phenotypic expression.

AB - An American family of English origin with an unusually early onset and long-duration form of Creutzfeldt-Jakob disease (CJD) had a heterozygous insert mutation in the region of repeating octapeptide coding sequences between codons 51 and 91 of the PRNP gene on chromosome 20. Affected members were 23 to 35 years old at the onset of illnesses that lasted from 4 to 13 years, yet experimental transmission of disease from the proband (11-year duration) produced a typically brief incubation period and duration of illness in each of three inoculated primates. Also, the PrP amyloid protein that accumulates in CJD brain was only barely detectable in extracted brain tissue from one case with massive spongiform change and was undetectable in another case with no spongiform change, perhaps because of epitope shielding by a configurational change in the protein induced by the mutation. Analysis of this and other families with similar inserts suggests that such mutations in the PRNP gene not only predispose to CJD, but also modify its phenotypic expression.

UR - http://www.scopus.com/inward/record.url?scp=0026606082&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026606082&partnerID=8YFLogxK

M3 - Article

VL - 42

SP - 422

EP - 427

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 2

ER -