1.Sleep disturbance associated with Smith-Magenis syndrome.
Chinese Journal of Medical Genetics 2021;38(12):1262-1265
Smith-Magenis syndrome (SMS) (OMIM #182290) is a rare genetic disorder with a prevalence of 1 in 25 000 live births. Approximately 90% of SMS patients have harbored a 3.7 Mb interstitial 17p11.2 deletion involving the RAI1 gene, while 10% of cases have carried pathogenic variants of the RAI1 gene. SMS is characterized by sleep disturbance, intellectual impairment, developmental delay, craniofacial and cardiovascular anomalies, obesity, self injury, aggressive and autistic-like behaviors. Most SMS patients have sleep disorders such as short total sleep time, frequent night waking, short sleep onset, and early morning waking. The sleep disturbance may aggravate with age and persist throughout life. Three mechanisms have been delineated. The first concern was the abnormal secretion of melatonin, with high levels during daytime and low levels at night. Evaluation of the integrity of the intrinsically photosensitive retinal ganglion cell (ipRGC)/melanopsin system has found that SMS patients showed dysfunction in the sustained component of the pupillary light responses to blue light. Synchronization of daily melatonin profile and its photoinhibition are dependent on the activation of melanopsin. Dysfunction of the retina-melanin system may be one of the causes of melatonin spectrum disorders. Secondly, dysregulation of circadian rhythm gene expression has also been noted in mice and SMS patients. Finally, there may be association between sleep deprivation symptoms and DNA methylation patterns, which has provided new insights for SMS-associated sleep disorders and symptoms alike. Treatment for SMS-related sleep disorders is administered primarily through medications like melatonin tablets, which can alleviate insomnia-related sleep difficulties, in particular externalizing behavior in children. Researchers are also actively exploring other treatments for SMS currently.
Animals
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Circadian Rhythm
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Humans
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Melatonin
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Mice
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Sleep
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Sleep Wake Disorders/genetics*
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Smith-Magenis Syndrome/genetics*
2.Association of CLOCK gene T3111C polymorphism with attention deficit hyperactivity disorder and related sleep disturbances in children.
Yin-Li CAO ; Qin-Tao CUI ; Cheng-He TANG ; Xiao CHANG
Chinese Journal of Contemporary Pediatrics 2012;14(4):285-288
OBJECTIVETo examine the association between CLOCK gene T3111C polymorphism with attention deficit hyperactivity disorder (ADHD) and ADHD related sleep disturbances in children.
METHODSOne hundred and sixty-six unrelated children with ADHD diagnosed according to DSM-IV criteria and a control group of 150 normal children were enrolled in this study. Parents filled out the Sleep Disturbance Scale for Children (SDSC). Genotype and allele frequencies of T3111C of the CLOCK gene were examined by PCR-restriction fragment length polymorphisms (PCR-RFLP).
RESULTSThere were significant differences in the genotype and allele frequencies of T3111C of the CLOCK gene between the ADHD and control groups (P<0.05). C allele frequency in the ADHD group was significantly higher than in the control group (χ2=7.254, P=0.007, OR=1.740, 95%CI=1.160-2.612). The ADHD children with sleep disturbances were found to have higher C allele frequency than those without sleep disturbances (χ2=13.052, P<0.001, OR=2.766, 95%CI=1.573-4.865).
CONCLUSIONSThere is an association between CLOCK gene T3111C polymorphism and both ADHD and related sleep disturbances in children. The individuals with C allele are susceptible to ADHD as well as ADHD related sleep disturbances.
Adolescent ; Attention Deficit Disorder with Hyperactivity ; complications ; genetics ; CLOCK Proteins ; genetics ; Child ; Child, Preschool ; Female ; Humans ; Male ; Polymorphism, Genetic ; Sleep Wake Disorders ; etiology ; genetics
3.Circadian Polymorphisms in Night Owls, in Bipolars, and in Non-24-Hour Sleep Cycles.
Daniel F KRIPKE ; Walter T KLIMECKI ; Caroline M NIEVERGELT ; Katharine M REX ; Sarah S MURRAY ; Tatyana SHEKHTMAN ; Gregory J TRANAH ; Richard T LOVING ; Heon Jeong LEE ; Min Kyu RHEE ; Farhad F SHADAN ; J Steven POCETA ; Shazia M JAMIL ; Lawrence E KLINE ; John R KELSOE
Psychiatry Investigation 2014;11(4):345-362
People called night owls habitually have late bedtimes and late times of arising, sometimes suffering a heritable circadian disturbance called delayed sleep phase syndrome (DSPS). Those with DSPS, those with more severe progressively-late non-24-hour sleep-wake cycles, and those with bipolar disorder may share genetic tendencies for slowed or delayed circadian cycles. We searched for polymorphisms associated with DSPS in a case-control study of DSPS research participants and a separate study of Sleep Center patients undergoing polysomnography. In 45 participants, we resequenced portions of 15 circadian genes to identify unknown polymorphisms that might be associated with DSPS, non-24-hour rhythms, or bipolar comorbidities. We then genotyped single nucleotide polymorphisms (SNPs) in both larger samples, using Illumina Golden Gate assays. Associations of SNPs with the DSPS phenotype and with the morningness-eveningness parametric phenotype were computed for both samples, then combined for meta-analyses. Delayed sleep and "eveningness" were inversely associated with loci in circadian genes NFIL3 (rs2482705) and RORC (rs3828057). A group of haplotypes overlapping BHLHE40 was associated with non-24-hour sleep-wake cycles, and less robustly, with delayed sleep and bipolar disorder (e.g., rs34883305, rs34870629, rs74439275, and rs3750275 were associated with n=37, p=4.58E-09, Bonferroni p=2.95E-06). Bright light and melatonin can palliate circadian disorders, and genetics may clarify the underlying circadian photoperiodic mechanisms. After further replication and identification of the causal polymorphisms, these findings may point to future treatments for DSPS, non-24-hour rhythms, and possibly bipolar disorder or depression.
Bipolar Disorder
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Case-Control Studies
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Comorbidity
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Depression
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Genetics
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Haplotypes
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Humans
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Melatonin
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Phenotype
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Photoperiod
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Polymorphism, Single Nucleotide
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Polysomnography
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Sleep Wake Disorders, Circadian Rhythm
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Strigiformes*