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).


METHODS
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 200Lys mutation in the largest CJD kindred yet reported. The clinical concept of familial CJD should be enlarged to include this unusual phenotype.
Bertoni
J M
JM
Department of Neurology, Creighton University, Omaha, Neb 68131-2197.
Brown
P
P
Goldfarb
L G
LG
Rubenstein
R
R
Gajdusek
D C
DC
D000328:Adult; D000368:Aged; D000682:Amyloid / Q000235:genetics; D001483:Base Sequence; D002890:Chromosomes, Human, Pair 20; D003062:Codon; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics*; D004277:DNA, Single-Stranded; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D013494:Supranuclear Palsy, Progressive / Q000235:genetics*
D000682:Amyloid; D003062:Codon; D004277:DNA, Single-Stranded