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

Toshio Iwase, Naofumi Kajimura, Makoto Uchiyama, Takashi Ebisawa, Kimio Yoshimura, Yuichi Kamei, Kayo Shibui, Keiko Kim, Yoshinao Kudo, Masaaki Katoh, Tsuyoshi Watanabe, Toru Nakajima, Yuji Ozeki, Mariko Sugishita, Toru Hori, Masaaki Ikeda, Ryoichi Toyoshima, Yuichi Inoue, Naoto Yamada, Kazuo MishimaMasahiko Nomura, Norio Ozaki, Masako Okawa, Kiyohisa Takahashi, Toshio Yamauchi

Research output: Contribution to journalArticlepeer-review

131 Citations (Scopus)


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. A T3111C polymorphism in the 3′-untranslated region of hClock, which had been reportedly associated with morning or evening preference for activity, was also investigated; the results showed that the 3111C allele frequency decreased in DSPS. Polymorphisms in the coding region of the hClock gene are unlikely to play an important role in the development of DSPS or N-24. The possible contribution of the T3111C polymorphism to DSPS susceptibility should be studied further.

Original languageEnglish
Pages (from-to)121-128
Number of pages8
JournalPsychiatry Research
Issue number2
Publication statusPublished - 2002
Externally publishedYes


  • Delayed sleep phase syndrome
  • Genetic screening
  • Missense mutation
  • Non-24-hour sleep-wake syndrome
  • Single-strand conformation polymorphism
  • Transcription factors

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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