An h <i>Per2</i> Phosphorylation Site Mutation in Familial Advanced Sleep Phase Syndrome

TLDR

Familial advanced sleep phase syndrome is an autosomal dominant circadian disorder that causes a ~4‑hour advance of sleep, temperature, and melatonin rhythms. The FASPS locus maps to chromosome 2q, where a serine‑to‑glycine missense mutation in the CKIε‑binding region of hPER2 leads to hypophosphorylation and shortens the circadian period.

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.