Mutation of the Human Circadian Clock Gene CRY1 in Familial Delayed Sleep Phase Disorder


Patke A., Murphy P. J., Onat O. E., Krieger A. C., Ozcelik T., Campbell S. S., ...Daha Fazla

CELL, cilt.169, sa.2, ss.203-215, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 169 Sayı: 2
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1016/j.cell.2017.03.027
  • Dergi Adı: CELL
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.203-215
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Hayır

Özet

Patterns of daily human activity are controlled by an intrinsic circadian clock that promotes similar to 24 hr rhythms in many behavioral and physiological processes. This system is altered in delayed sleep phase disorder (DSPD), a common form of insomnia in which sleep episodes are shifted to later times misaligned with the societal norm. Here, we report a hereditary form of DSPD associated with a dominant coding variation in the core circadian clock gene CRY1, which creates a transcriptional inhibitor with enhanced affinity for circadian activator proteins Clock and Bmal1. This gain-of-function CRY1 variant causes reduced expression of key transcriptional targets and lengthens the period of circadian molecular rhythms, providing a mechanistic link to DSPD symptoms. The allele has a frequency of up to 0.6%, and reverse phenotyping of unrelated families corroborates late and/or fragmented sleep patterns in carriers, suggesting that it affects sleep behavior in a sizeable portion of the human population.