Delayed sleep phase disorder (DSPD) is a common sleep disorder in which a person’s sleep/wake cycle is shifted beyond the usual or typically considered normal rhythm. Affected people are “night owls”: their internal body clock is set differently, they fall asleep late at night, find it difficult to get up at conventional times in the morning and they experience daytime sleepiness.

Researchers have now identified in a proband a dominant variant in the cryptochrome circadian clock 1 (CRY1) gene as the genetic cause of DSPD. CRY1 is a key component of the molecular clock comprising multiple interacting genes and feedback loops that regulate the endogenous circadian rhythm to a cycle length of about 24 hours. The researchers now report in Cell that the newly identified mutation in CRY1 creates a transcriptional inhibitor with enhanced affinity for circadian activator proteins Clock and Bmal1. The gain of function of CRY1 causes reduced expression of key transcriptional targets and lengthens the period of circadian molecular rhythms.

The CRY1 allele is reported in genomic databases with a frequency of up to 0.6%. By reverse phenotyping, the researchers determined that further carriers of the variant from unrelated families also displayed aberrant sleep patterns, and they conclude that the identified variant may affect sleep behavior in a sizeable portion of the human population.