Evidence map›Paper›PMID 22578325›Full record

ArticleAmerican journal of human genetics2012

Smith-Magenis syndrome results in disruption of CLOCK gene transcription and reveals an integral role for RAI1 in the maintenance of circadian rhythmicity.

Stephen R Williams, Deborah Zies, Sureni V Mullegama, Michael S Grotewiel, Sarah H Elsea

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 2 pooled it
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 2 syntheses or guidelines pooled it, 115 citations in OpenAlex.

  1. Pooled it
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  11. Pentanucleotide Repeat Insertions in RAI1 Cause Benign Adult Familial Myoclonic Epilepsy Type 8.Movement disorders : official journal of the Movement Disorder Society · 2024
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  19. Dream enactment behavior: review for the clinician.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2020
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Stephen R WilliamsDepartment of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, 23298, USA.
Deborah Zies
Sureni V Mullegama
Michael S Grotewiel
Sarah H Elsea
Virginia Commonwealth University · USSalk Institute for Biological Studies · USUniversity of Mary Washington · US

Funding

Molecular Analysis of del(17)(p11.2)R01HD038534 · NICHD · VIRGINIA COMMONWEALTH UNIVERSITY · PI ELSEA, SARAH H. · 2001 to 2005
$1.2M
NICHD NIH HHS R01 HD038534
6 · The paper itself

Abstract

Haploinsufficiency of RAI1 results in Smith-Magenis syndrome (SMS), a disorder characterized by intellectual disability, multiple congenital anomalies, obesity, neurobehavioral abnormalities, and a disrupted circadian sleep-wake pattern. An inverted melatonin rhythm (i.e., melatonin peaks during the day instead of at night) and associated sleep-phase disturbances in individuals with SMS, as well as a short-period circadian rhythm in mice with a chromosomal deletion of Rai1, support SMS as a circadian-rhythm-dysfunction disorder. However, the molecular cause of the circadian defect in SMS has not been described. The circadian oscillator temporally orchestrates metabolism, physiology, and behavior largely through transcriptional modulation. Data support RAI1 as a transcriptional regulator, but the genes it might regulate are largely unknown. Investigation into the role that RAI1 plays in the regulation of gene transcription and circadian maintenance revealed that RAI1 regulates the transcription of circadian locomotor output cycles kaput (CLOCK), a key component of the mammalian circadian oscillator that transcriptionally regulates many critical circadian genes. Data further show that haploinsufficiency of RAI1 and Rai1 in SMS fibroblasts and the mouse hypothalamus, respectively, results in the transcriptional dysregulation of the circadian clock and causes altered expression and regulation of multiple circadian genes, including PER2, PER3, CRY1, BMAL1, and others. These data suggest that heterozygous mutation of RAI1 and Rai1 leads to a disrupted circadian rhythm and thus results in an abnormal sleep-wake cycle, which can contribute to an abnormal feeding pattern and dependent cognitive performance. Finally, we conclude that RAI1 is a positive transcriptional regulator of CLOCK, pinpointing a novel and important role for this gene in the circadian oscillator.

Indexed as

Circadian RhythmTranscription, GeneticAnimalsCLOCK ProteinsFemaleFibroblastsGene Expression RegulationHeterozygoteHumansHypothalamusMaleMiceMice, TransgenicMutationOligonucleotide Array Sequence AnalysisOscillometryCLOCK ProteinsRAI1 protein, humanRai1 protein, mouseRNA, Small InterferingTrans-ActivatorsTranscription Factors

Identifiers

PMID22578325
PMCPMC3370274
OpenAlexW2012653631

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.