A pilot study of a genetic CJD risk factor (E200K) in the general Slovak population.

Abstract

Creutzfeldt-Jakob disease (CJD) is a fatal, incurable human transmissible spongiform encephalopathy, or prion disease. Classical CJD has been recognised since the 1920s. CJD occurs in three forms : sporadic, of unknown origin, genetic, related to disease specific point mutations, insertions or deletions of the prion protein gene (PRNP) and iatrogenic (iCJD), caused by accidental transmission of the disease in the course of medical or surgical treatment. A new variant of CJD, which is causally related to bovine spongiform encephalopathy (BSE) was first described by Will et al. in 1996. The risk of horizontal transmission of CJD has been confirmed in classical [1] as well as in variant CJD. Precautions and measures to prevent iCJD are focused mainly on clinical CJD patients, but a potential risk from preclinical cases, for example asymptomatic carriers of CJDspecific mutations of the PRNP, cannot be excluded. These carriers represent a ‘‘genetic CJD-risk group’’ in the general population. More than 37 disease-specific mutations have been described in the PRNP coding sequence. The most common point mutation associated with genetic CJD is at codon 200 (E200K) [2]. While in the majority of countries the genetic form represents about 10–15 % of all CJD patients, in Slovakia it has never been \65 % since 1975. [3]. Except for one case with the R208H mutation, all 202 genetic CJD patients in Slovakia carry the E200K mutation (gCJD). Most of these cases are concentrated in two clusters in central Slovakia [4]. Voluntary genetic testing of healthy blood relatives has revealed that 35 % carry the E200K mutation [3]. Besides the risk of gCJD (59 % of carriers will develop the disease) (3), ‘‘healthy’’ carriers could act as a source of iatrogenic infection. To our knowledge, the prevalence of the mutation E200K has not been studied. The aim of this pilot study is to investigate the occurrence and frequency of asymptomatic carries of E200K in the Slovak general population, comparing the areas of focal accumulation of gCJD with extrafocal areas, i.e. comparison of regions with contrasting incidence rates of gCJD. In the present study the occurrence of the mutation E200K and the distribution of the M129 V polymorphism of PRNP were analysed in 2,662 subjects with no known link to patients with gCJD. Tested were DNA from two different sources: 1. anonymised DNA samples of newborns provided by Slovak Newborn Screening Center were from regions with different incidence of gCJD: 1a) 893 samples from two focal accumulations (clusters) of gCJD in central Slovakia (mean incidence of gCJD 3.55/million) and 1b) 757 samples from extrafocal regions in western and E. Mitrova D. Kosorinova M. Gajdos I. Tomeckova Medical Faculty, Slovak Medical University, Bratislava, Slovakia