NR AFBC
AU Haltia,M.; Kovanen,J.; Goldfarb,L.G.; Brown,P.; Gajdusek,D.C.
TI Familial Creutzfeldt-Jakob disease in Finland: epidemiological, clinical, pathological and molecular genetic studies.
QU European Journal of Epidemiology 1991 Sep; 7(5): 494-500
PT journal article
AB In 1974-1984 30 patients died with a diagnosis of Creutzfeldt-Jakob disease (CJD) in Finland (annual mortality rate of CJD 0.9 per million population for the years 1979-1984). Six of these patients (20%) were familial, all belonging to the same kindred. The pedigree now includes 15 affected members in four generations, and the occurrence of disease is consistent with an autosomal dominant mode of inheritance. The clinical features of CJD in this family are in most respects typical of the familial disease described elsewhere. However, the mean age at onset is 47, periodic EEG activity has not been observed, and the mean duration of illness of 27.5 months is longer than usual for either familial or sporadic CJD. Neuropathological examination of brain biopsy and autopsy specimens revealed spongiform change without amyloid plaques, and brain tissue from one patient transmitted disease to a capuchin monkey. In an analysis of the histocompatibility antigens of the family, CJD was not linked with a single haplotype, but at least 12 out of 13 CJD patients shared the HLA antigen A28. Molecular genetic studies disclosed a new G-to-A mutation in codon 178 of the PRNP gene (resulting in a substitution of asparagine for aspartic acid) in the DNA of eight family members with CJD but not in any of ten currently healthy first degree relatives of the patients, or 86 controls. The codon 178 mutation thus seems to co-segregate with CJD in this family. Linkage analysis gave a LOD score value of 3.6.
IN
1979-1984 starben in Finnland 0,9 von 1 Million Menschen an der Creutzfeldt-Jakob-Krankheit. Davon waren 20% erblich bedingt. Der Erbgang in 4 Generationen einer Familie spricht für eine autosomal dominante Vererbung. Die Symptome traten durchschnittlich mit 47 Jahren auf und dauerten mit im Mittel 27,5 Monaten ungewöhnlich lange. Dennoch wurden bei einer Autopsie keine amyloiden Plaques gefunden. Hirnmaterial eines Patienten übertrug die Krankheit auf einen Affen. Bei den kranken und nicht bei den gesunden Familienmitgliedern wurde eine Mutation von Asparaginsäure zu Asparagin im Codon 178 gefunden.
Es wurde keine Verbindung zwischen CJD und einem bestimmten Histokompatibilitätsantigenhaplotyp festgestellt, aber mindestens 12 von 13 CJD Patienten hatten das Histokompatibilitätsantigen A28.
MH Adult; Animal; Brain/pathology/physiopathology; Codon; Creutzfeldt-Jakob; Syndrome/*epidemiology/genetics/pathology/physiopathology; DNA/analysis; Electroencephalography; Finland/epidemiology; HLA Antigens/analysis; Human; Middle Age; Molecular Biology; Pedigree; PrPsc Proteins; Prions/genetics
AD M.Haltia, J.Kovanen, Departments of Pathology and Neurology, University of Helsinki, Haartmaninkatu 3, SF-00290 Helsinki, Finland; L.G.Goldfarb, P.Brown, D.C.Gajdusek, Laboratory of CNS Studies and Laboratory of Molecular and Cellular Neurobiology (Section of Receptor Biochemistry and Molecular Biology), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
SP englisch
PO Italien
OR Prion-Krankheiten H