Familial Creutzfeldt-Jakob disease in Finland: epidemiological, clinical, pathological and molecular genetic studies

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...

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Bibliographic Details
Published inEuropean journal of epidemiology Vol. 7; no. 5; p. 494
Main Authors Haltia, M, Kovanen, J, Goldfarb, L G, Brown, P, Gajdusek, D C
Format Journal Article
LanguageEnglish
Published Netherlands 01.09.1991
Subjects
Adult
Animals
Brain - pathology
Brain - physiopathology
Codon
Creutzfeldt-Jakob Syndrome - epidemiology
Creutzfeldt-Jakob Syndrome - genetics
Creutzfeldt-Jakob Syndrome - pathology
Creutzfeldt-Jakob Syndrome - physiopathology
DNA - analysis
Electroencephalography
Finland - epidemiology
HLA Antigens - analysis
Humans
Middle Aged
Molecular Biology
Pedigree
Prions - genetics
PrPSc Proteins
Finland
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Summary: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.
ISSN:0393-2990
DOI:10.1007/bf00143128