Iatrogenic Creutzfeldt-Jakob disease: an example of the interplay between ancient genes and modern medicine.

We tested DNA from 15 centrally infected cases of iatrogenic Creutzfeldt-Jakob disease (CJD) (dura mater or corneal homografts and stereotactic EEG electrodes), 11 peripherally infected cases (native human growth hormone or gonadotrophin), and 110 control individuals for the presence of mutations in the chromosome 20 amyloid gene. No patient or control had any of the known pathogenic point or insert mutations found in familial disease, but allelic homozygosity at polymorphic codon 129 was present in all but two (92%) of the 26 patients, compared with 54 (50%) of the 110 controls (p < 0.001). Pooled data from all identified and tested cases of iatrogenic disease yielded a worldwide total of 56 patients, of whom all but four were homozygous at codon 129 (p < 0.001). These findings support the thesis that homozygosity at codon 129 enhances susceptibility to iatrogenic infections of both central and peripheral origin, with evident implications for the population of dura mater homograft and pituitary hormone recipients whose lives have been complicated by the possibility of exposure to the infectious agent of CJD.