INHERITED CREUTZFELDT-JAKOB-DISEASE IN A BRITISH FAMILY ASSOCIATED WITH A NOVEL 144-BASE-PAIR INSERTION OF THE PRION PROTEIN GENE

A case of familial Creutzfeldt-Jakob disease associated with a 144 bas e pair insertion in the open reading frame of the prion protein gene i s described. Sequencing of the mutated allele showed an arrangement of six octapeptide repeats, distinct from that of a recently described B ritish family with an insertion of similar size. Thirteen years previo usly the brother of the proband had died from ''Huntington's disease'' , but re-examination of his neuropathology revealed spongiform encepha lopathy and anti-prion protein immunocytochemistry gave a positive res ult. The independent evolution of at least two distinct pathological 1 44 base pair insertions in Britain is proposed. The importance of main taining a high index of suspicion of inherited Creutzfeldt-Jakob disea se in cases of familial neurodegenerative disease is stressed.