Clinical features of Fatal Familial Insomnia: Phenotypic variability in relation to a polymorphism at codon 129 of the prion protein gene

Pasquale Montagna, Pietro Cortelli, Patrizia Avoni, Paolo Tinuper, Giuseppe Plazzi, Roberto Gallassi, Francesco Portaluppi, Jean Julien, Claude Vital, Marie Bernadette Delisle, Pierluigi Gambelti, Elio Lugaresi

Research output: Contribution to journalArticle

Abstract

Fatal Familial Insomnia is a hereditary prion disease characterized by a mutation at codon 178 of the prion protein gene cosegregating with the methionine polymorphism at codon 129 of the mutated allele. It is characterized by disturbances of the wake-sleep cycle, dysautonomia and somatomotor manifestations (myoclonus, ataxia, dysarthria, spasticity). PET studies disclose severe thalamic and additionally cortical hypometabolism. Neuropathology shows marked neuronal loss and gliosis in the thalamus, especially the medio-dorsal and anterior-ventral nuclei, olivary hypertrophy and some spongiosis of the cerebral cortex. Detailed analysis of 14 cases from 5 unrelated families showed that patients ran either a short (9.1 + 1.1 months) or a prolonged (30.8 + 21.3 months) clinical course according to whether they were homozygote met/met or heterozygote met/val at codon 129. Moreover, homozygotes had more prominent oneiric episodes, insomnia and dysautonomia at onset, whereas heterozygotes showed ataxia and dysarthria at onset, earlier sphincter loss and epileptic Grand Mal seizures; they also displayed more extensive cortical involvement on PET and at postmortem examination. Our data suggest that the phenotype expression of Fatal Familial Insomnia is related, at least partly, to the polymorphism at codon 129 of the prion protein-gene.

Original languageEnglish
Pages (from-to)515-520
Number of pages6
JournalBrain Pathology
Volume8
Issue number3
Publication statusPublished - 1998

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine

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    Montagna, P., Cortelli, P., Avoni, P., Tinuper, P., Plazzi, G., Gallassi, R., Portaluppi, F., Julien, J., Vital, C., Delisle, M. B., Gambelti, P., & Lugaresi, E. (1998). Clinical features of Fatal Familial Insomnia: Phenotypic variability in relation to a polymorphism at codon 129 of the prion protein gene. Brain Pathology, 8(3), 515-520.