Familial Creutzfeldt-Jakob Disease (Codon 200 Mutation) With Supranuclear Palsy

Objective.—To identify a possible gene defect in a large kindred with atypical Creutzfeldt-Jakob disease (CJD). Subjects.—Over 360 kindred members, with and without progressive dementia. Methods.—Family, hospital, and clinic records were reviewed. The DNA was extracted from paraffin-embedded brain tissue of two deceased patients, and from blood leukocytes of nine healthy persons at risk. DNA was subjected to polymerase chain reaction and then analyzed by restriction endonuclease and single nucleotide primer extension. Results.—Nine family members had progressive fatal neurological disease consistent with CJD without myoclonus or typical electroencephalographic findings. Supranuclear gaze palsy was present in all five patients who underwent eye examinations. Two neuropathologically confirmed cases and five of nine at-risk family members had an identical mutation (GAG to AAG, glutamic acid to lysine) in codon 200 of the amyloid gene (PRNP) on chromosome 20. Conclusions.—Clinically atypical CJD with early supranuclear gaze palsy but without myoclonus or characteristic electroencephalographic periodicity patterns is associated with the codon 200^Lys mutation in the largest CJD kindred yet reported. The clinical concept of familial CJD should be enlarged to include this unusual phenotype.