Mutation of the human circadian clock gene CRY1 in familial delayed sleep phase disorder
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[1] Rockefeller University
Rockefeller University
Estados Unidos
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[2] Faculty of Science
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- Localización: Cell, ISSN 0092-8674, Vol. 169, Nº. 2, 2017, págs. 203-215
- Idioma: inglés
- Texto completo no disponible (Saber más ...)
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Resumen
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.
