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Science 291 (5506): 1040-1043

Copyright © 2001 by the American Association for the Advancement of Science

An hPer2 Phosphorylation Site Mutation in Familial Advanced Sleep Phase Syndrome

Kong L. Toh,1* Christopher R. Jones,23* Yan He,4 Erik J. Eide,5 William A. Hinz,5 David M. Virshup,56 Louis J. Ptácek,27dagger Ying-Hui Fu4

Familial advanced sleep phase syndrome (FASPS) is an autosomal dominant circadian rhythm variant; affected individuals are "morning larks" with a 4-hour advance of the sleep, temperature, and melatonin rhythms. Here we report localization of the FASPS gene near the telomere of chromosome 2q. A strong candidate gene (hPer2), a human homolog of the period gene in Drosophila, maps to the same locus. Affected individuals have a serine to glycine mutation within the casein kinase Iepsilon (CKIepsilon ) binding region of hPER2, which causes hypophosphorylation by CKIepsilon in vitro. Thus, a variant in human sleep behavior can be attributed to a missense mutation in a clock component, hPER2, which alters the circadian period.

1 Department of Human Genetics,
2 Department of Neurology,
3 University Hospital Sleep Disorders Center,
4 Department of Neurobiology and Anatomy,
5 Department of Oncological Sciences and the Huntsman Cancer Institute Center for Children,
6 Department of Pediatrics,
7 Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: ptacek{at}genetics.utah.edu


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M. Takimoto, A. Hamada, A. Tomoda, S. Ohdo, T. Ohmura, H. Sakato, J. Kawatani, T. Jodoi, H. Nakagawa, H. Terazono, et al. (2005)
Am J Physiol Regulatory Integrative Comp Physiol 289, R1273-R1279
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The circadian cycle: daily rhythms from behaviour to genes: First in the Cycles Review Series.
M. Merrow, K. Spoelstra, and T. Roenneberg (2005)
EMBO Rep. 6, 930-935
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Transient short free running circadian rhythm in a case of aneurysm near the suprachiasmatic nuclei.
K E Bloch, T Brack, and A Wirz-Justice (2005)
J. Neurol. Neurosurg. Psychiatry 76, 1178-1180
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Timing and Consolidation of Human Sleep, Wakefulness, and Performance by a Symphony of Oscillators.
D.-J. Dijk and M. von Schantz (2005)
J Biol Rhythms 20, 279-290
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