An h <i>Per2</i> Phosphorylation Site Mutation in Familial Advanced Sleep Phase Syndrome
Kong Leong Toh, Christopher R. Jones, Yan He(Institute of Neurobiology), Erik J. Eide(Huntsman Cancer Institute), William A. Hinz(Huntsman Cancer Institute), David M. Virshup(Huntsman Cancer Institute), Louis J. Ptáček(Howard Hughes Medical Institute), Ying‐Hui Fu(Institute of Neurobiology)
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Abstract
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.