Editing Advanced sleep phase disorder (section)

=== Discovery ===
In 1999, [[Louis Ptáček]] conducted a study at the University of Utah in which he coined the term ''familial advanced sleep phase disorder'' after identifying individuals with a genetic basis for an advanced sleep phase. The first patient evaluated during the study reported "disabling early evening sleepiness" and "early morning awakening"; similar symptoms were also reported in her family members. Consenting relatives of the initial patient were evaluated, as well as those from two additional families. The clinical histories, sleep logs and [[actigraphy]] patterns of subject families were used to define a hereditary circadian rhythm variant associated with a short endogenous (i.e. internally-derived) period. The subjects demonstrated a phase advance of sleep-wake rhythms that was distinct not only from control subjects, but also to sleep-wake schedules widely considered to be conventional. The subjects were also evaluated using the [[Morningness–eveningness questionnaire|Horne-Östberg questionnaire]], a structured self-assessment questionnaire used to determine morningness-eveningness in human circadian rhythms. The Horne-Östberg scores of first-degree relatives of affected individuals were higher than those of 'marry-in' spouses and unrelated control subjects. While much of morning and evening preference is heritable, the allele causing FASPS was hypothesized to have a quantitatively larger effect on clock function than the more common genetic variations that influence these preferences. Additionally, the circadian phase of subjects was determined using plasma [[melatonin]] and body core temperature measurements; these rhythms were both phase-advanced by 3–4 hours in FASPS subjects compared with control subjects. The Ptáček group also constructed a [[Pedigree chart|pedigree]] of the three FASPS kindreds which indicated a clear [[Dominance (genetics)|autosomal dominant]] transmission of the sleep phase advance.<ref>{{Cite journal|last1=Jones|first1=Christopher R.|last2=Campbell|first2=Scott S.|last3=Zone|first3=Stephanie E.|last4=Cooper|first4=Fred|last5=DeSano|first5=Alison|last6=Murphy|first6=Patricia J.|last7=Jones|first7=Bryan|last8=Czajkowski|first8=Laura|last9=Ptček|first9=Louis J.|date=1999|title=Familial advanced sleep-phase syndrome: A short-period circadian rhythm variant in humans|journal=Nature Medicine|language=en|volume=5|issue=9|pages=1062–1065|doi=10.1038/12502|pmid=10470086|s2cid=14809619|issn=1078-8956}}</ref>

In 2001, the research group of [[Phyllis C. Zee]] phenotypically characterized an additional family affected with ASPS. This study involved an analysis of sleep/wake patterns, diurnal preferences (using a Horne-Östberg questionnaire), and the construction of a pedigree for the affected family. Consistent with established ASPS criteria, the evaluation of subject sleep architecture indicated that the advanced sleep phase was due to an alteration of circadian timing rather than an exogenous (i.e. externally-derived) disruption of sleep homeostasis, a mechanism of [[Neuroscience of sleep|sleep regulation]]. Furthermore, the identified family was one in which an ASPS-affected member was present in every generation; consistent with earlier work done by the Ptáček group, this pattern suggests that the phenotype segregates as a single gene with an autosomal dominant mode of inheritance.<ref name=":13">{{Cite journal|last1=Reid|first1=Kathryn J.|last2=Chang|first2=Anne-Marie|last3=Dubocovich|first3=Margarita L.|last4=Turek|first4=Fred W.|last5=Takahashi|first5=Joseph S.|last6=Zee|first6=Phyllis C.|date=1 July 2001|title=Familial Advanced Sleep Phase Syndrome|journal=Archives of Neurology|language=en|volume=58|issue=7|pages=1089–94|doi=10.1001/archneur.58.7.1089|pmid=11448298|issn=0003-9942|doi-access=free}}</ref>

In 2001, the research groups of Ptáček and [[Ying-Hui Fu]] published a genetic analysis of subjects experiencing the advanced sleep phase, implicating a mutation in the [[Casein kinase 1|CK1]]-binding region of [[PER2]] in producing the FASPS behavioral phenotype.<ref name=":42">{{Cite journal|last=Toh|first=K. L.|date=9 February 2001|title=An hPer2 Phosphorylation Site Mutation in Familial Advanced Sleep Phase Syndrome|journal=Science|volume=291|issue=5506|pages=1040–1043|doi=10.1126/science.1057499|pmid=11232563|bibcode=2001Sci...291.1040T|s2cid=1848310}}</ref> FASPS is the first disorder to link known core clock genes directly with human circadian sleep disorders.<ref>{{Cite journal|last1=Takahashi|first1=Joseph S.|last2=Hong|first2=Hee-Kyung|last3=Ko|first3=Caroline H.|last4=McDearmon|first4=Erin L.|date=2008|title=The genetics of mammalian circadian order and disorder: implications for physiology and disease|journal=Nature Reviews Genetics|language=en|volume=9|issue=10|pages=764–775|doi=10.1038/nrg2430|issn=1471-0056|pmc=3758473|pmid=18802415}}</ref> As the PER2 mutation is not exclusively responsible for causing FASPS, current research has continued to evaluate cases in order to identify new mutations that contribute to the disorder.{{citation needed|date=July 2021}}