Mutation screening of the human Clock gene in circadian rhythm sleep disorders.

We tested whether the human Clock (hClock) gene, one of the essential components of the circadian oscillator, is implicated in the vulnerability to delayed sleep phase syndrome (DSPS) and non-24-hour sleep-wake syndrome (N-24). Screening in the entire coding region of the hClock gene with PCR amplification revealed three polymorphisms, of which two predicted the amino acid substitutions R533Q and H542R. The frequencies of the R533Q and H542R alleles in patients with DSPS or N-24 were very low and not significantly different from those in control subjects.