Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene

Goldfarb, L. G., Brown, P., McCombie, W. R., Goldgaber, D., Swergold, G. D., Wills, P. R., Cervenakova, L., Baron, H., Gibbs Jr, C. J., Gajdusek, D. C. (1991) Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene. Proceedings of the National Academy of Sciences of the United States of America, 88 (23). pp. 10926-10930. ISSN 00278424 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/1683708

Abstract

The PRNP gene, encoding the amyloid precursor protein that is centrally involved in Creutzfeldt-Jakob disease (CJD), has an unstable region of five variant tandem octapeptide coding repeats between codons 51 and 91. We screened a total of 535 individuals for the presence of extra repeats in this region, including patients with sporadic and familial forms of spongiform encephalopathy, members of their families, other neurological and non- neurological patients, and normal controls. We identified three CJD families (in each of which the proband's disease was neuropathologically confirmed and experimentally transmitted to primates) that were heterozygous for alleles with 10, 12, or 13 repeats, some of which had 'wobble' nucleotide substitutions. We also found one individual with 9 repeats and no nucleotide substitutions who had no evidence of neurological disease. These observations, together with data on published British patients with 11 and 14 repeats, strongly suggest that the occurrence of 10 or more octapeptide repeats in the encoded amyloid precursor protein predisposes to CJD.

Item Type: Paper
Uncontrolled Keywords: amyloid precursor protein prion protein article controlled study creutzfeldt jakob disease disease predisposition human human tissue major clinical study prion priority journal Adult Alleles Amino Acid Sequence Amyloid beta-Protein Precursor Animal Base Sequence Brain Case Report Cloning, Molecular Creutzfeldt-Jakob Syndrome Crossing Over (Genetics) Female Male Middle Age Molecular Sequence Data Mutation Oligodeoxyribonucleotides Phenotype Polymerase Chain Reaction Primates Prions PrPSc Proteins Repetitive Sequences, Nucleic Acid
Subjects: diseases & disorders > congenital hereditary genetic diseases
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
diseases & disorders > mental disorders > genetic disorders
CSHL Authors:
Communities: CSHL labs > McCombie lab
Depositing User: Matt Covey
Date Deposited: 23 Apr 2013 15:51
Last Modified: 23 Apr 2013 15:51
PMCID: PMC53045
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28250

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