Iatrogenic Creutzfeldt‐Jakob disease

Brown, Paul A.; Červen̆áková, Larisa; Goldfarb, L. G.; McCombie, W. Richard; Rubenstein, Richard; Will, Robert; Pocchiari, Maurizio; Martínez‐Lage, Juan F.; Scalici, C.; Masullo, Carlo; Graupera, G.; Ligan, J.; Gajdusek, D. Carleton

doi:10.1212/wnl.44.2.291

Cited by 134 publications

(46 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although not in itself pathogenic, it has been shown to influence susceptibility to iatrogenic and sporadic forms of TSE and to affect age at onset and duration of illness in familial TSE; in association with a pathogenic mutation in codon 178, the entire disease phenotype is altered (5)(6)(7)(8)(9)(10)(11).…”

Section: Discussionmentioning

confidence: 99%

Phenotype-genotype studies in kuru: Implications for new variant Creutzfeldt–Jakob disease

Červen̆áková

Goldfarb

Garruto

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

137

View full text Add to dashboard Cite

The PRNP polymorphic (methionine/valine) codon 129 genotype inf luences the phenotypic features of transmissible spongiform encephalopathy. All tested cases of new variant Creutzfeldt-Jakob disease (nvCJD) have been homozygous for methionine, and it is conjectural whether different genotypes, if they appear, might have distinctive phenotypes and implications for the future ''epidemic curve'' of nvCJD. Genotype-phenotype studies of kuru, the only other orally transmitted transmissible spongiform encephalopathy, might be instructive in predicting the answers to these questions. We therefore extracted DNA from blood clots or sera from 92 kuru patients, and analyzed their codon 129 PRNP genotypes with respect to the age at onset and duration of illness and, in nine cases, to detailed clinical and neuropathology data. Homozygosity at codon 129 (particularly for methionine) was associated with an earlier age at onset and a shorter duration of illness than was heterozygosity, but other clinical characteristics were similar for all genotypes. In the nine neuropathologically examined cases, the presence of histologically recognizable plaques was limited to cases carrying at least one methionine allele (three homozygotes and one heterozygote). If nvCJD behaves like kuru, future cases (with longer incubation periods) may begin to occur in older individuals with heterozygous codon 129 genotypes and signal a maturing evolution of the nvCJD ''epidemic.'' The clinical phenotype of such cases should be similar to that of homozygous cases, but may have less (or at least less readily identified) amyloid plaque formation.

show abstract

Section: Discussionmentioning

confidence: 99%

Phenotype-genotype studies in kuru: Implications for new variant Creutzfeldt–Jakob disease

Červen̆áková

Goldfarb

Garruto

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

137

View full text Add to dashboard Cite

show abstract

“…42 -44 Examples are the CCR5 gene for HIV infection, 45 malaria and heterozygosity for sickle cell anemia 46 or variant Creutzfeld -Jakob disease and a Gene -environment interaction A Dempfle et al polymorphism in codon 129 of the prion protein gene PRNP. 47 In these examples, individuals with certain genotypes have a much lower risk for infection or progression to serious disease. Infectious disease studies usually include only individuals at high risk of infection (assumed to be exposed).…”

Section: Study Designs For G â Ementioning

confidence: 99%

Gene–environment interactions for complex traits: definitions, methodological requirements and challenges

et al. 2008

View full text Add to dashboard Cite

Genetic and environmental risk factors and their interactions contribute to the development of complex diseases. In this review, we discuss methodological issues involved in investigating gene -environment (G Â E) interactions in genetic -epidemiological studies of complex diseases and their potential relevance for clinical application. Although there are some important examples of interactions and applications, the widespread use of the knowledge about G Â E interaction for targeted intervention or personalized treatment (pharmacogenetics) is still beyond current means. This is due to the fact that convincing evidence and high predictive or discriminative power are necessary conditions for usefulness in clinical practice. We attempt to clarify conceptual differences of the term 'interaction' in the statistical and biological sciences, since precise definitions are important for the interpretation of results. We argue that the investigation of G Â E interactions is more rewarding for the detailed characterization of identified disease genes (ie at advanced stages of genetic research) and the stratified analysis of environmental effects by genotype or vice versa. Advantages and disadvantages of different epidemiological study designs are given and sample size requirements are exemplified. These issues as well as a critical appraisal of common methodological concerns are finally discussed.

show abstract

“…This polymorphism is a key determinant of susceptibility to sporadic (10) and acquired (8,11) prion diseases and may affect age at onset (12)(13)(14). Based on the analysis of 300 sporadic CJD subjects, Parchi et al (14) identified six distinct clinicopathological variants of sCJD, which appeared to be specified largely by the genotype at codon 129 and the physiochemical properties of PrP Sc .…”

mentioning

confidence: 99%

Methionine 129 Variant of Human Prion Protein Oligomerizes More Rapidly than the Valine 129 Variant

Tahiri-Alaoui

Gill

Disterer

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

The human PrP gene (PRNP) has two common alleles that encode either methionine or valine at codon 129. This polymorphism modulates disease susceptibility and phenotype of human transmissible spongiform encyphalopathies, but the molecular mechanism by which these effects are mediated remains unclear. Here, we compared the misfolding pathway that leads to the formation of ␤-sheet-rich oligomeric isoforms of the methionine 129 variant of PrP to that of the valine 129 variant. We provide evidence for differences in the folding behavior between the two variants at the early stages of oligomer formation. We show that Met 129 has a higher propensity to form ␤-sheet-rich oligomers, whereas Val 129 has a higher tendency to fold into ␣-helical-rich monomers. An equimolar mixture of both variants displayed an intermidate folding behavior. We show that the oligomers of both variants are initially a mixture of ␣-and ␤-rich conformers that evolve with time to an increasingly homogeneous ␤-rich form. This maturation process, which involves no further change in proteinase K resistance, occurs more rapidly in the Met 129 form than the Val 129 form. Although the involvement of such ␤-rich oligomers in prion pathogenesis is speculative, the misfolding behavior could, in part, explain the higher susceptibility of individuals that are methionine homozygote to both sporadic and variant CreutzfeldtJakob disease.

show abstract

Iatrogenic Creutzfeldt‐Jakob disease

Cited by 134 publications

References 13 publications

Phenotype-genotype studies in kuru: Implications for new variant Creutzfeldt–Jakob disease

Phenotype-genotype studies in kuru: Implications for new variant Creutzfeldt–Jakob disease

Gene–environment interactions for complex traits: definitions, methodological requirements and challenges

Methionine 129 Variant of Human Prion Protein Oligomerizes More Rapidly than the Valine 129 Variant

Contact Info

Product

Resources

About