Coffin‐Lowry syndrome and schizophrenia: a family report

Collacott, R. A.; Warrington, Jill; Young, Ian

doi:10.1111/j.1365-2788.1987.tb01356.x

Cited by 9 publications

(3 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CLS patients being dependent, they are unlikely to develop drug abuse. Interestingly, schizophrenia has been reported in some CLS female patients (Collacott et al. 1987).…”

Section: Discussionmentioning

confidence: 99%

Dopaminergic system dysregulation in the mrsk2_KO mouse, an animal model of the Coffin‐Lowry syndrome

Pereira

Gruss

Braun

et al. 2008

Journal of Neurochemistry

View full text Add to dashboard Cite

The Coffin-Lowry syndrome, a rare syndromic form of X-linked mental retardation, is caused by loss-of-function mutations in the hRSK2 (RPS6KA3) gene. To further investigate RSK2 (90-kDa ribosomal S6 kinase) implication in cognitive processes, a mrsk2_KO mouse has previously been generated as an animal model of Coffin-Lowry syndrome. The aim of the present study was to identify possible neurochemical dysregulation associated with the behavioral and morphological abnormalities exhibited by mrsk2_KO mice. A cortical dopamine level increase was found in mrsk2_KO mice that was accompanied by an over-expression of dopamine receptor of type 2 and the dopamine transporter. We also detected an increase of total and phosphorylated extracellular regulated kinase that may be responsible for the increased level of tyrosine hydroxylase phosphorylation also observed. By taking into consideration previously reported data, our results strongly suggest that the dopaminergic dysregulation in mrsk2_KO mice may be caused, at least in part, by tyrosine hydroxylase hyperactivity. This cortical hyperdopaminergia may explain some non-cognitive but also cognitive alterations exhibited by mrsk2_KO mice.

show abstract

“…CLS patients being dependent, they are unlikely to develop drug abuse. Interestingly, schizophrenia has been reported in some CLS female patients (Collacott et al. 1987).…”

Section: Discussionmentioning

confidence: 99%

Dopaminergic system dysregulation in the mrsk2_KO mouse, an animal model of the Coffin‐Lowry syndrome

Pereira

Gruss

Braun

et al. 2008

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…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.…”

mentioning

confidence: 99%

“…. As some individuals with CLS exhibit a schizophrenia-like psychosis (R. A Collacott et al, 1987;U. Sivagamasundari et al, 1994;.…”

mentioning

confidence: 99%

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

Zhu

Farrell

et al. 2017

Preprint

View full text Add to dashboard Cite

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

show abstract

A syndromic form of X-linked mental retardation: the Coffin-Lowry syndrome

2002

View full text Add to dashboard Cite

Coffin-Lowry syndrome is a well characterised entity and a detailed clinical examination usually allows diagnosis. However, recognising it in very young children is often difficult since physical characteristics are mild and not specific. In addition, most cases are sporadic. Screening for ribosomal S6 kinase mutations is essential in most cases to confirm the diagnosis as well as for genetic counselling.

show abstract

Coffin‐Lowry syndrome and schizophrenia: a family report

Cited by 9 publications

References 8 publications

Dopaminergic system dysregulation in the mrsk2_KO mouse, an animal model of the Coffin‐Lowry syndrome

Dopaminergic system dysregulation in the mrsk2_KO mouse, an animal model of the Coffin‐Lowry syndrome

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

A syndromic form of X-linked mental retardation: the Coffin-Lowry syndrome

Contact Info

Product

Resources

About