NR ABUY
AU Brown,P.; Cervenakova,L.; Goldfarb,L.G.; McCombie,W.R.; Rubenstein,R.; Will,R.G.; Pocchiari,M.; Martinez-Lage,J.F.; Scalici,C.; Masullo,C.; Graupera,G.; Ligan,J.; Gajdusek,D.C.
TI Iatrogenic Creutzfeldt-Jakob Disease: An example of the interplay between ancient genes and modern medicine
QU Neurology 1994 Feb; 44(2): 291-3
PT journal article
AB 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.
IN
Bei 15 durch stereotaktische EEG-Elektroden oder Transplantationen von harter Gehirnhaut oder Augenhornhaut infizierten und bei 11 durch menschliches Wachstumshormon oder Gonadotropin infizierten Creutzfeldt-Jakob-PatientInnen, sowie bei 110 Kontrollpersonen wurde keine der von erblichen Creutzfeldt-Jakob-Krankheitsfällen bekannten pathogenen Punkt- oder Insertionsmutationen des Amyloidgenes auf dem Chromosom 20 gefunden. Während nur 54 der 110 Kontrollpersonen (50%) bezüglich des polymorphen Codons 129 homozygot waren, traf dies auf 24 der 26 untersuchten Creutzfeldt-Jakob-Infizierten (92%) zu. Von den weltweit 56 durch ärztliche Maßnahmen infizierten Creutzfeldt-Jakob-PatientInnen sind alle bis auf 4 homozygot bezüglich des Codons 129 im Prionproteingen.
Infektionsquelle Codon 129 Genotypen
Met/Met Met/Val Val/Val
harte Hirnhaut 11 0 1
Augenhornhaut 1 0 0
Stereotaktische EEG-Elektroden 1 1 0
Wachstumshormone 5 1 3
Gonadotropine 2 0 0
Kontrollen 45 56 9
MH Amyloid/*genetics; Base Sequence; Brain/metabolism; *Chromosomes, Human, Pair 20; Codon; Comparative Study; Corneal Transplantation/adverse effects; Creutzfeldt-Jakob Syndrome/blood/*etiology/*genetics; DNA/analysis/blood/isolation & purification; DNA Primers; Deoxyribonucleases, Type II Site-Specific; Dura Mater/transplantation; Electroencephalography/adverse effects; Genotype; Gonadotropins/adverse effects/therapeutic use; Growth Hormone/adverse effects/therapeutic use; Homozygote; Human; *Iatrogenic Disease; Methionine; Molecular Sequence Data; Open Reading Frames; *Point Mutation; Restriction Mapping; Transplantation, Homologous/adverse effects; Valine
AD Paul Brown (pwb@codon.nih.gov), Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
SP englisch
PO USA
OR Prion-Krankheiten 2