The association between Coffin‐Lowry syndrome and psychosis: a family study

Sivagamasundari, Umapathy; Fernando, Heshan; Jardine, Philip; Rao, Jay; Lunt, Peter G.; Jayewardene, S. L. W.

doi:10.1111/j.1365-2788.1994.tb00436.x

Cited by 17 publications

(4 citation statements)

References 7 publications

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“…CLS is characterized by moderate to severe mental retardation, pathognomonic craniofacial and skeletal deformities, growth retardation (Lowry et al, 1971), movement disorders (Stephenson et al, 2005), cardiovascular disorders, and a schizophrenia-like psychosis in heterozygote females (Hanauer and Young, 2002; Sivagamasundari et al, 1994). Recent availability of RSK2 knockout mice provide an animal model to probe the pathological causes of CLS.…”

Section: Introductionmentioning

confidence: 99%

Insights into the regulation of 5-HT2A serotonin receptors by scaffolding proteins and kinases

Allen

Yadav²,

Roth³

2008

Neuropharmacology

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SUMMARY 5-HT2A serotonin receptors are essential molecular targets for the actions of LSD-like hallucinogens and atypical antipsychotic drugs. 5-HT2A serotonin receptors also mediate a variety of physiological processes in peripheral and central nervous systems including platelet aggregation, smooth muscle contraction, and the modulation of mood and perception. Scaffolding proteins have emerged as important regulators of 5-HT2A receptors and our recent studies suggest multiple scaffolds exist for 5-HT2A receptors including PSD95, arrestin, and caveolin. In addition, a novel interaction has emerged between p90 ribosomal S6 kinase and 5-HT2A receptors which attenuates receptor signaling. This article reviews our recent studies and emphasizes the role of scaffolding proteins and kinases in the regulation of 5-HT2A trafficking, targeting and signaling.

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Section: Introductionmentioning

confidence: 99%

Insights into the regulation of 5-HT2A serotonin receptors by scaffolding proteins and kinases

Allen

Yadav²,

Roth³

2008

Neuropharmacology

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“…Individuals with CLS frequently display the symptoms of autism spectrum disorder as well as psychosis (U. Sivagamasundari et al, 1994). CLS is caused by a variety of heterogeneous loss-of-function mutations in the ribosomal protein S6 kinase, 90kDa, polypeptide 3 (RPS6KA3) gene, which maps to Xp22.2 (E. Trivier et al, 1996).…”

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confidence: 99%

“…Loss-of-function of RSK2 in humans leads to Coffin-Lowry syndrome, which includes behavioral characteristics of a schizophrenia-like psychosis in some individuals (R. A. Collacott et al, 1987;U. Sivagamasundari et al, 1994;A.…”

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confidence: 99%

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Cell-type selective deletion of RSK2 reveals insights into altered signaling in Coffin-Lowry Syndrome

Zhu

Farrell

et al. 2017

Preprint

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Coffin-Lowry syndrome (CLS) is an X-linked syndromic form of mental retardation characterized by various skeletal dysmorphisms, moderate to severe mental retardation, and in . CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/156257 doi: bioRxiv preprint first posted online Jun. 26, 2017; some cases, psychosis. CLS is caused by loss-of-function mutations of the p90 ribosomal S6 kinase 2 (RPS6KA3) gene encoding a growth factor-regulated serine/threonine kinase, ribosomal S6 kinase 2 (RSK2). We previously identified RSK2 as a novel interacting protein that tonically inhibits 5-HT2A receptor signaling by phosphorylating Ser-314 within the third intracellular loop.To determine if RSK2 inhibits 5-HT2A receptor signaling in vivo and whether disruption of RSK2 could lead to schizophrenia-like behaviors -as is seen in some CLS patients -we genetically disrupted the function of RSK2 either globally or selectively in forebrain pyramidal neurons in mice. Both global and forebrain-selective RSK2 deletion augmented the locomotor responses to the psychotomimetic drugs phencyclidine (PCP) and amphetamine (AMPH).Significantly, forebrain-selective deletion of RSK2 augmented 5-HT2A receptor signaling as exemplified by enhanced 5-HT2A-mediated c-fos activation and head-twitch response without altering the levels or distribution of 5-HT2A receptor protein. Thus, RSK2 modulates 5HT2A receptor function in vivo, and disruption of RSK2 leads to augmented psychostimulant-induced responses reminiscent of those seen in many animal models of schizophrenia. These findings strengthen the association between 5-HT2A receptor dysfunction and psychosis, and provide a potential mechanism underlying the schizophrenia-like symptoms present in some CLS patients. Highlights: Global and cell-type-specific RSK2 knock-out mice were assessed behaviorally and pharmacologically  Augmentation of amphetamine and PCP locomotor responses were seen in both global and forebrain-specific RSK2 KO mice  Augmentation of 5-HT2A serotonin receptor function but not number was also observed . CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/156257 doi: bioRxiv preprint first posted online Jun. 26, 2017;  These alterations reveal insights into mechanisms potentially responsible for behavioral sequlae of Coffin-Lowry Syndrome

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Coffin‐Lowry Syndrome

Hunter

2005

Management of Genetic Syndromes

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Coffin‐Lowry syndrome is a distinctive X‐linked dominantly inherited condition that has a birth prevalence of about 1/50,000 and is caused by mutations in the RDS6KA3 gene. The hemizygous male presents with significant mental retardation and a facial appearance characterized by a prominent forehead and supraorbital ridges; down‐slanting palpebrae and hypertelorism; a distinctive nose with a low bridge, thick septum, small and anteverted nares; and full and patulous lips with the lower lip everted. The hands are soft and hyperextensible with tapering fingers, and there are a number of minor and nonspecific radiographic changes that may aid in the diagnosis. Progressive kyphoscoliosis can be an important complication. Clinical expression in the heterozygous female can range from completely normal intelligence and appearance, through mild degrees of intellectual impairment and facial dysmorphia, to expression equaling that in the male. There is evidence to suggest a significant risk of premature death, primarily related to pulmonary and cardiac complications but in some cases remaining unexplained.

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The association between Coffin‐Lowry syndrome and psychosis: a family study

Cited by 17 publications

References 7 publications

Insights into the regulation of 5-HT2A serotonin receptors by scaffolding proteins and kinases

Insights into the regulation of 5-HT2A serotonin receptors by scaffolding proteins and kinases

Cell-type selective deletion of RSK2 reveals insights into altered signaling in Coffin-Lowry Syndrome

Coffin‐Lowry Syndrome

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