FATAL FAMILIAL INSOMNIA - PHENOTYPIC DIFF ERENCE DETERMINED BY POLYMORPHISM AT CODON-129

We report a new case of fatal familial insomnia, characterized by muta tion of codon 178 of prion protein gene and by methionine homozygosity at codon 129. This homozygotic form is revealed by severe insomnia an d dysautonomia. Microscopic lesions, neuronal loss and gliosis, are li mited to a part of the thalamus (dorso-median and anterior nucleii). F rom genetic analysis of a blood stain, retrospective diagnosis of fata l familial insomnia was made on the patient's mother who died three ye ars earlier with, clinical features suggestive of Creutzfeldt Jakob di sease. In her case the mutation of the codon 178 was associated with t he methionine/valine heterozygosity at codon 129. This genotypic polym orphism may account for conformation variation of prion protein isofor m that could explain clinical and pathological differences.