Creutzfeldt-Jakob disease segregating in a three generation Danish family

A three generation family is presented in which rapidly progressive, early- onset Creutzfeldt-Jakob disease without typical EEG changes segregates as a n autosomal dominant disease. An aspartic acid to asparagine mutation at co don 178 of the prion gene, PRNP, cosegregates with the disease. As expected , the disease allele also carries the valine codon of the polymorphic valin e/methionine codon 129 of the gene. In family members homozygous for this v aline codon the disease was more rapidly progressive than in a heterozygous family member, who had a variant clinical phenotype. Definite neuropatholo gical diagnosis required prion staining with specific antibodies.