Familial advanced sleep phase syndrom

The results obtained with the model for the mammalian circadian clock provide cues for circadian-rhythm-related sleep disorders in humans [117]. Thus permanent phase shifts in LD conditions could account for (a) the familial advanced sleep phase syndrome (FASPS) associated with PER hypopho-sphorylation [118, 119] and (b) the delayed sleep phase syndrome, which is also related to PER [120]. People affected by FASPS fall asleep around 7 30 p.m. and awake around 4 30 a.m. The duration of sleep is thus normal, but the phase is advanced by several hours. Moreover, the autonomous period measured for circadian rhythms in constant conditions is shorter [121]. The model shows that a decrease in the activity of the kinase responsible for PER phosphorylation is indeed accompanied by a reduction of the circadian period in continuous darkness and by a phase advance upon entrainment of the rhythm by the LD cycle [114]. 

C. R. Jones, S. S. Campbell, S. E. Zone, E. Cooper, A. DeSano, P. J. Murphy, B. Jones, L. Czajkowski, and L. J. Ptacek, Familial advanced sleep-phase syndrome A short-period circadian rhythm variant in humans. Nat. Med. 5, 1062-1065 (1999). 

Tei H, Okamura H, Shigeyoshi Y et al 1997 Circadian oscillation of a mammalian homologue of the Drosophila period gene. Nature 389 512—516 Toh KL, J ones CR, He Y et al 2001 An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. Science 291 1040-1043... 

Toh KL, Jones CR, He Y et al2001 An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. Science 291 1040-1043... 

Familial advanced and delayed sleep phase syndromes can both be attributed to mammalian per mutations in a region of the PER protein, presumably a CKIe binding domain (Ebisawa et al 2001, Toh et al 2001). Because a phosphorylation disorder might cause some sleep syndromes, the establishment of a system with which to assay post-translational modifications of PER protein has recently received considerable focus. 

Familial advanced (Toh et al 2001) and delayed (Ebisawa et al 2001) sleep phase syndrome is caused by disorders of the molecular circadian clock. To verify the... 

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