An hPer2 phosphorylation site mutation in familiar advanced sleep phase syndrome

Familiar 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 I epsilon (CKI epsilon) binding region of hPER2, which causes hypophosphorylation by CKI epsilon 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.