| Institution: | (1) Austrian Reference Centre for Human Prion Diseases (OERPE) and Institute of Neurology, Medical University AKH 4J, Waehringer Guertel 18-20, 1097 Vienna, Austria;(2) Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy;(3) Department of Epidemiology and Biostatistics, Erasmus MC, PO Box 1738, 3000, DR, Rotterdam, The Netherlands;(4) Department of Pathology, The University of Melbourne, Parkville, Victoria, 3052, Australia;(5) Blood Safety Surveillance and Health Care Acquired Infections Division, The Centre for Infectious Disease Prevention and Control, LCDC Building, PL 0601E2, Tunney’s Pasture, Ottawa, ON, K1A 0L2, Canada;(6) National Laboratory for Host Genetic and Prion Diseases, NML, PHAC, Health, Winnipeg, MB, Canada;(7) U.360 INSERM, Hopital de la Salpetriere, 75651 Paris, Cedex 13, France;(8) Department of Neurology, Georg-August-Universität Göttingen, Robert-Koch Strasse 40, 37075 Gottingen, Germany;(9) Institute of Neuropathology, University of Munich, Marchioninistr. 17, 81377 Munich, Germany;(10) Departamento de Epidemiologia Aplicada, Instituto de Salud Carlos III, Centro Nacional de Epidemiologia, Calle Sinesio Delgado 6, 28029 Madrid, Spain;(11) Centro National de Microbiologia Unidad de Encefalopatias Espongiformes, Ctra Majadakonda—Pozuelo km2, 28220, Majadakonda, Madrid, Spain;(12) Swiss National Reference Centre for Prion Diseases, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland;(13) National CJD Surveillance Unit, Western General Hospital, Edinburgh, EH4 2XU, UK;(14) Institute of Preventive and Clinical Medicine, Research Base of Slovak Medical University, National Reference Centre for Prion Diseases, Limbova 14, 833 01 Bratislava, Slovakia;(15) Present address: National Institute of Psychiatry and Neurology and Hungarian Reference Centre for Human Prion Disease, Budapest, Hungary |
| Abstract: | A total of 10–15% of human transmissible spongiform encephalopathies (TSEs) or prion diseases are characterised by disease-specific mutations in the prion protein gene (PRNP). We examined the phenotype, distribution, and frequency of genetic TSEs (gTSEs) in different countries/geographical regions. We collected standardised data on gTSEs between 1993 and 2002 in the framework of the EUROCJD collaborative surveillance project. Our results show that clinicopathological phenotypes include genetic Creutzfeldt–Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann–Sträussler–Scheinker disease (GSS). Genetic TSE patients with insert mutation in the PRNP represent a separate group. Point and insertional mutations in the PRNP gene varies significantly in frequency between countries. The commonest mutation is E200K. Absence of a positive family history is noted in a significant proportion of cases in all mutation types (12–88%). FFI and GSS patients develop disease earlier than gCJD. Base pair insertions associated with the Creutzfeldt–Jakob disease (CJD) phenotype, GSS, and FFI cases have a longer duration of illness compared to cases with point mutations and gCJD. Cerebrospinal fluid 14-3-3 immunoassay, EEG, and MRI brain scan are useful in the diagnosis of CJD with point mutations, but are less sensitive in the other forms. Given the low prevalence of family history, the term “gTSE” is preferable to “familial TSE”. Application of genetic screening in clinical practice has the advantage of early diagnosis and may lead to the identification of a risk of a TSE.Gábor G. Kovács and Maria Propolo Contributed equally |
