title: Two pedigrees of familial advanced sleep phase syndrome in Japan.
abstract: OBJECTIVE
  To determine whether a known missense mutation (bp2106 A/G) in hPer2 (a human homolog of the Drosophila period gene) for familial advanced sleep phase syndrome in a Caucasian family is involved in Japanese familial advanced sleep phase syndrome pedigrees.
  
  
  RESULTS
  We identified 2 new Japanese families with advanced sleep phase syndrome, and a systematic survey was carried out in 28 relatives of theses 2 families. A total of 9 affected subjects were identified. The affected members showed significantly strong morningness tendencies compared with the unaffected members in various circadian parameters including the Horne-Ostberg Morningness-Eveningness Questionnaire score (77.3 +/- 4.8 vs 57.5 +/- 7.6, p < 0.001), average sleep-onset time (20:45 +/- 75 min vs 23:16 +/- 64 min, p < 0.02), and average wake time (4:55 +/- 38 min vs 6:13 +/- 25 min, p < 0.01), as well as saliva dim-light melatonin-onset time (20:15 +/- 21 min vs 22:25 +/- 65 min, p < 0.02). DNA samples were obtained from 7 affected and 7 unaffected subjects. None of the tested subjects possessed the missense mutation (bp2106 A/G) in hPer2. Furthermore, there is no significant linkage between affected subjects with hPer2 region by 2-point mapping and by direct sequencing of 23 exons of hPer2.
  
  
  CONCLUSIONS
  These findings support the notion of genetic heterogeneity of familial advanced sleep phase syndrome cases in humans. The search for more familial advanced sleep phase syndrome cases and for loci other than hPer2 are necessary to further examine the roles of circadian-related genes in genetically determined human circadian rhythm disorders.
authors.affiliation: Department of Neuropsychiatry, Akita University School of Medicine, Akita-city, Japan.
authors.forename: Kohtoku
authors.initials: K
authors.lastname: Satoh
authors.forename: Kazuo
authors.initials: K
authors.lastname: Mishima
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Inoue
authors.forename: Takashi
authors.initials: T
authors.lastname: Ebisawa
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000328:Adult; D002648:Child; D005091:Exons; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D009687:Nuclear Proteins; D010375:Pedigree; D056950:Period Circadian Proteins; D017354:Point Mutation / Q000235:genetics; D011506:Proteins / Q000235:genetics; D020178:Sleep Disorders, Circadian Rhythm / Q000208:ethnology* / Q000235:genetics*; D011795:Surveys and Questionnaires; D013577:Syndrome; D014157:Transcription Factors
chemical_list: D009687:Nuclear Proteins; C421902:PER2 protein, human; D056950:Period Circadian Proteins; D011506:Proteins; D014157:Transcription Factors