This report describes familial advanced sleep phase syndrome 2 (FASPS2), which is a subtype of advanced sleep phase syndrome; FASPS2 exhibits autosomal dominant inheritance. The human gene implicated in this disease is CSNK1D, which encodes casein kinase 1 delta, a ubiquitous serine/threonine-specific protein kinase. There is one high-scoring fly ortholog, dco, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and classical alleles have been generated. Dmel\dco is also a high-scoring ortholog of the human gene CSNK1E.
Multiple UAS constructs of the human Hsap\CSNK1D gene have been introduced into flies, including wild-type CSNK1D and a CSNK1D gene carrying a mutational lesion associated with FASPS2. Variant(s) implicated in human disease tested (as transgenic human gene, CSNK1D): the T44A variant form has been introduced into flies. Expression of the T44A variant results in a lengthening of the circadian locomotor activity period length.
Homozygous loss-of-function mutations of Dmel\dco result in lethality, typically during the larval stage. Less severe alleles or genotypes result in circadian rhythm defects. Many physical and genetics interactions have been described for Dmel\dco; see below and in the dco gene report.
[updated Jul. 2017 by FlyBase; FBrf0222196]
Advanced sleep phase syndrome is a sleep disorder that involves an altered circadian rhythm resulting in falling asleep in early evening and awaking very early in the morning.
Advanced sleep phase syndrome is characterized by very early sleep onset and offset (summary by Jones et al., 1999, pubmed:10470086). [From MIM:604348, 2016.05.24]
[ADVANCED SLEEP PHASE SYNDROME, FAMILIAL, 2; FASPS2](https://omim.org/entry/615224)
[CASEIN KINASE I, DELTA; CSNK1D](https://omim.org/entry/600864)
Familial advanced sleep phase syndrome 2 (FASPS2) is a disorder characterized by very early sleep onset and offset. Individuals are 'morning larks' with a 4 hours advance of the sleep, temperature and melatonin rhythms. [From UniProt, uniprot:P48730 2016.05.25]
Familial advanced sleep phase syndrome 2 (FASPS2) has been reported in a 3-generation family with autosomal dominant transmission of FASPS. Fifteen family members were interviewed for their typical work and vacation sleep-wake schedules, and 5 were identified with FASPS. In the absence of competing psychosocial demands, both the average sleep onset time ( 18:12 +/- 1.4 hours vs 23:24 +/- 1.1 hour) and final wake time ( 04:06 +/- 0.7 hour vs 08:00 +/- 1.6 hours) of these subjects were significantly earlier (p less than 0.0001) than those of the 9 unaffected family members. Affected individuals reported onset of FASPS between early childhood and the mid-teen years (Xu et al., 2005, pubmed:15800623). Five of the mutation carriers with FASPS2 in this family additionally had migraine with or without aura. One mutation carrier who did not have FASPS also had migraine. However, 3 family members who were offspring of carriers but did not carry the mutation also had migraine. A second unrelated family also segregated FASPS and migraine with or without aura. Transgenic mice carrying the T44A mutation were more sensitive to pain after treatment with the migraine trigger nitroglycerin, and showed a reduced threshold for cortical spreading depression, which is believed to be the physiologic analog of migraine aura, as well as greater arterial dilation during cortical spreading depression (Brennan et al., 2013, pubmed:23636092). [From MIM:615224, 2016.05.24]
This form of autosomal dominant advanced sleep phase syndrome, FASPS2, is caused by heterozygous mutations in the CSNK1D gene. Identified mutations include T44A and H46R. [From MIM:615224 and MIM:600864, 2016.05.25]
The CSNKID gene encodes casein kinase 1 delta, a member of the casein kinase I (CKI) gene family whose members have been implicated in the control of cytoplasmic and nuclear processes, including DNA replication and repair. The encoded protein may also be involved in the regulation of apoptosis, circadian rhythm, microtubule dynamics, chromosome segregation, and p53-mediated effects on growth. The encoded protein is highly similar to the mouse and rat CK1 delta homologs. [provided by RefSeq, Feb 2014]
Many to one: 2 human to 1 Drosophila.
Ortholog of human CSNK1D and CSNK1E (1 Drosophila to 2 human).
Dmel\Lam shares 67% identity and 75% similarity with human CSNK1D, and 66% identity and 77% similarity with human CSNK1E.
