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)
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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: | 1991 |
| Date Deposited: | 23 Apr 2013 15:51 |
| Last Modified: | 30 Sep 2019 14:56 |
| PMCID: | PMC53045 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/28250 |
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