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Updated: Aug 12, 2026
Noninvasive, High-throughput Determination of Sleep Duration in Rodents
Published on: April 18, 2018
Clinical and genetic studies of fatal familial insomnia
A T Reder1, A S Mednick, P Brown
1Department of Neurology, University of Chicago School of Medicine, IL, USA.
Abstract:
We report a 42-year-old man who, for 8 months, had intermittent motor abnormalities and mild difficulty falling asleep. A diagnosis of fatal familial insomnia (FFI) became evident over the next 6 months when he developed progressive insomnia, myoclonus, sympathetic hyperactivity, and dementia. The amyloid or prion protein (PrP) genotype showed features typically seen in FFI, with a 178Asn mutation and a 129Met polymorphism. There was also a deletion of one octapeptide repeat, suggesting that the association of 178Asn mutation with the 129Met polymorphism is not due to "founder effect." Western immunoblot showed a trace of protease-resistant PrP in the thalamus--which had the most significant neuronal loss and gliosis--a moderate amount of PrP in the fronto-temporal area, and no detectable protein elsewhere in the brain. Endocrine studies showed that a circadian modulation of hormonal levels could be maintained despite a near-total absence of sleep. Administration of gamma-hydroxybutyrate induced a remarkable increase in slow-wave sleep.
Insights
Fatal familial insomnia (FFI) is a rare prion disease. This study details a patient with FFI, highlighting genetic factors and potential therapeutic responses.
Area of Science:
- Neuroscience
- Genetics
Background:
- Fatal familial insomnia (FFI) is a rare, autosomal dominant prion disease characterized by progressive insomnia, autonomic dysfunction, and dementia.
- The disease is caused by mutations in the prion protein gene (PRNP).
Observation:
- A 42-year-old man presented with 8 months of motor abnormalities and sleep difficulties, progressing to severe insomnia, myoclonus, sympathetic hyperactivity, and dementia over 6 months.
- Genetic analysis revealed the typical FFI genotype (178Asn mutation and 129Met polymorphism) with an additional octapeptide repeat deletion.
- Western immunoblotting detected protease-resistant prion protein (PrP) predominantly in the thalamus, correlating with neuronal loss and gliosis.
Findings:
- The 178Asn mutation and 129Met polymorphism association in FFI may not solely be due to a founder effect, as suggested by the octapeptide repeat deletion.
- Despite near-total sleep deprivation, circadian modulation of hormone levels was maintained.
- Gamma-hydroxybutyrate administration significantly increased slow-wave sleep in the patient.
Implications:
- This case provides insights into the genetic heterogeneity of FFI and the distribution of prion protein in the brain.
- The findings suggest potential therapeutic avenues targeting sleep regulation in prion diseases.
- Further research is warranted to explore the role of gamma-hydroxybutyrate in managing sleep disturbances in neurodegenerative conditions.
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