Atypical Creutzfeldt-Jakob Disease in an American Family with an Insert Mutation in the PRNP Amyloid Precursor Gene.

Authors

Paul Brown MD
Lev G. Goldfarb MD
W. Richard McCombie PhD
Ana Nieto MD
D Squillacote MD
William Sheremata MD
Brian W. Little MD, PhD, Lehigh Valley Health NetworkFollow
Marck S. Godec MD
Clarence J. Gibbs Jr PhD
D.Carleton Gajdusek MD

Publication/Presentation Date

1-31-1992

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.

Volume

42

Issue

2

First Page

422

Last Page

427

ISSN

0028-3878

Published In/Presented At

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.

Disciplines

Neurology

PubMedID

1736177

Department(s)

Department of Medicine

Document Type

Article