Mutation of the Human Circadian Clock Gene CRY1 in Familial Delayed Sleep Phase Disorder. Academic Article uri icon

Overview

MeSH

  • Circadian Rhythm
  • Exons
  • Female
  • Gene Deletion
  • Humans
  • Male
  • Middle Aged
  • Pedigree

MeSH Major

  • Cryptochromes
  • Sleep Disorders, Circadian Rhythm

abstract

  • Patterns of daily human activity are controlled by an intrinsic circadian clock that promotes ∼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. Copyright © 2017 Elsevier Inc. All rights reserved.

publication date

  • April 6, 2017

has subject area

  • Circadian Rhythm
  • Cryptochromes
  • Exons
  • Female
  • Gene Deletion
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Sleep Disorders, Circadian Rhythm

Research

keywords

  • Case Reports
  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5479574

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2017.03.027

PubMed ID

  • 28388406

Additional Document Info

start page

  • 203

end page

  • 215.e13

volume

  • 169

number

  • 2