NR AEGZ
AU Gabizon,R.; Rosenman,H.; Meiner,Z.; Kahana,I.; Kahana,E.; Shugart,Y.; Ott,J.; Prusiner,S.B.
TI Mutation in codon 200 and polymorphism in codon 129 of the prion protein gene in Libyan Jews with Creutzfeldt-Jakob disease
QU Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 1994 Mar 29; 343(1306): 385-90
IA http://www.journals.royalsoc.ac.uk/media/3g267u4vuhcqywc3ng86/contributions/t/n/1/1/tn1122m1546v55l0.pdf
PT journal article
AB Various mutations in the prion protein (PrP) gene are associated with Creutzfeldt-Jakob disease (CJD), a transmissible fatal neurodegenerative disorder. Among Libyan Jews, CJD is a familial disease with an incidence about 100 times higher than the worldwide population. CJD in this community segregates with a point mutation at codon 200 of the PrP gene which causes the substitution of lysine for glutamate. This mutation was found in all definitely affected individuals and yields a maximum lod score of 4.85. Some healthy elderly mutation carriers above 65 years of age were identified, suggesting partial penetrance. Homozygous patients have the same disease pattern and age of onset as heterozygous patients, which argues that CJD associated with the codon 200 lysine mutation is a true dominant disorder. In the caucasian population, Palmer et al. (1991) reported an association between homozygosity in a polymorphic site at codon 129 of the PrP gene, coding for either valine or methionine, with a tendency to acquire the sporadic or iatrogenic forms of CJD, as well as with disease age of appearance in the genetic type. The incidence of the polymorphism at codon 129 in the control Libyan population is similar to the one found in the caucasian population. In the Libyan CJD patients, the codon 200 mutation is within a Met129-encoding allele. The incidence of the Met allele is significantly higher in the affected pedigrees than in the control Libyan population; however, no difference was detected between CJD patients, codon 200 healthy carriers, and their normal family members. Homozygosity at codon 129 did not correlate with age of onset or the clinical course in the Libyan Jewish patients. Our finding suggests that the codon 200 mutation causing CJD in Libyan Jews occurred in an isolated pedigree, and has not propagated since to the general Libyan Jewish community.
IN Bei relativ vielen lybischen Juden bewirkt der vererbte Austausch einer Glutaminsäure gegen ein Lysin an der Position 200 des Prionproteins ein im Vergleich zur restlichen Weltbevölkerung 100-fach häufigeres Auftreten der Creutzfeldt-Jakob-Krankheit. Bezüglich des Codons 200 homozygote Mutationsträger scheinen nicht früher oder schwerer als heterozygote zu erkranken. Dies spricht für eine dominante Erbkrankheit. Es wurden aber auch schon einige mehr als 65 Jahre alte gesunde Mutationsträger gefunden. In der untersuchten Population wurde kein Zusammenhang zwischen dem Auftreten oder Einsetzen der Erkrankung und der Homozygotie bezüglich des Codons 129 des Prionproteins gefunden. Das Methion-129-Allel zwar bei erkrankten Personen deutlich häufiger gefunden, erklärt wird dies aber mit einer Kopplung der pathogenen Mutation des Codons 200 an das Allel Met-129.
MH Adult; Aged; Alleles; Base Sequence; Codon/genetics; Creutzfeldt-Jakob Syndrome/*genetics; DNA Primers/genetics; Female; Genotype; Heterozygote; Homozygote; Human; Jews/genetics; Libya; Linkage (Genetics); Male; Middle Age; Molecular Sequence Data; Phenotype; Point Mutation; Polymorphism (Genetics); PrPsc Proteins; Prions/*genetics; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.
AD Department of Neurology, Hadassah University Hospital, Jerusalem, Israel.
SP englisch
PO England
OR Prion-Krankheiten G
ZF kritische Zusammenfassung von Roland Heynkes