title: Genetic prion disease: the EUROCJD experience.
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.
authors.affiliation: Austrian Reference Centre for Human Prion Diseases (OERPE), Vienna, Austria.
authors.forename: Gábor G
authors.initials: GG
authors.lastname: Kovács
authors.forename: Maria
authors.initials: M
authors.lastname: Puopolo
authors.forename: Anna
authors.initials: A
authors.lastname: Ladogana
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pocchiari
authors.forename: Herbert
authors.initials: H
authors.lastname: Budka
authors.forename: Cornelia
authors.initials: C
authors.lastname: van Duijn
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Collins
authors.forename: Alison
authors.initials: A
authors.lastname: Boyd
authors.forename: Antonio
authors.initials: A
authors.lastname: Giulivi
authors.forename: Mike
authors.initials: M
authors.lastname: Coulthart
authors.forename: Nicole
authors.initials: N
authors.lastname: Delasnerie-Laupretre
authors.forename: Jean Philippe
authors.initials: JP
authors.lastname: Brandel
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: Jesus
authors.initials: J
authors.lastname: de Pedro-Cuesta
authors.forename: Miguel
authors.initials: M
authors.lastname: Calero-Lara
authors.forename: Markus
authors.initials: M
authors.lastname: Glatzel
authors.forename: Adriano
authors.initials: A
authors.lastname: Aguzzi
authors.forename: Matthew
authors.initials: M
authors.lastname: Bishop
authors.forename: Richard
authors.initials: R
authors.lastname: Knight
authors.forename: Girma
authors.initials: G
authors.lastname: Belay
authors.forename: Robert
authors.initials: R
authors.lastname: Will
authors.forename: Eva
authors.initials: E
authors.lastname: Mitrova
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000134:cerebrospinal fluid / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging; D004252:DNA Mutational Analysis; D005060:Europe; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D017354:Point Mutation; D015995:Prevalence; D017096:Prion Diseases / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors / Q000134:cerebrospinal fluid / Q000235:genetics*; D011859:Radiography; D012307:Risk Factors
chemical_list: D000682:Amyloid; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors