Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Creutzfeldt-Jakob Disease, sporadic Form and new Variant [A81.0]

OMIM numbers: 123400, 176640 (PRNP)

Dr. rer. biol. hum. Soheyla Chahrokh-Zadeh,
Dr. rer. nat. Christoph Marschall

Scientific Background

While cases of the sporadic form of Creutzfeldt-Jacob disease (sCJD) were already reported in the 70s, a new variant of the disease (vCJD), probably transmitted to humans, was first observed in 1996. Most patients developed the disease in Great Britain during the time of BSE. Earliest onset of the disease was 12 years; the average age of death was 29 years.

Due to the similarity of the signs and symptoms of sCJD and vCJD and the familial form of CJD, an association with the prion protein PrP was suspected and therefore the encoding PRNP gene of vCJD patients examined systematically. Most of the studied patients showed a genetic variant at codon 129 of the PRNP gene, the PRNP-M129V polymorphism (rs1799990) (homozygosity for the amino acid methionine in position 129). In the case of Kuru, another form of transmitted spongiform encephalopathy which the prion protein is also involved in, heterozygosity for methionine in position 129 of the PRNP gene is associated with a late onset of the disease. Approximately 40% of all Caucasians are homzygous for methionine, 50% heterozygous and 10% homozygous for valin in position 129. According to previous findings, valin at codon 129 seems to provide protection regarding vCJD or prolong the onset of the disease.