Mutation of the Human Circadian Clock Gene CRY1 in Familial Delayed Sleep Phase Disorder
Highlights • A human subject with DSPD with a variation in CRY1 has altered circadian rhythms • Proband kindred and unrelated carrier families display aberrant sleep patterns • The allele alters circadian molecular rhythms • The genetic variation enhances CRY1 function as a transcriptional inhibitor Summary 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 ...