CDKL5 is agene that provides instructions for making aprotein calledcyclin-dependent kinase-like 5 also known asserine/threonine kinase 9 (STK9) that is essential for normal brain development. Mutations in the gene can cause deficiencies in the protein. The gene regulates neuronal morphology through cytoplasmic signaling and controlling gene expression.[5] The CDKL5 protein acts as akinase, which is an enzyme that changes the activity of other proteins by adding a cluster ofoxygen andphosphorus atoms (aphosphate group) at specific positions. Researchers are currently working to determine which proteins are targeted by the CDKL5 protein.[6]
The CDKL5protein acts as akinase, which is an enzyme that modulates the activity of other proteins by adding a phosphate group to specific positions. The CDKL5 protein regulates neuronal morphology through cytoplasmic signaling and by controlling gene expression, playing a crucial role in the development and maintenance of the nervous system.
Studies have shown that the CDKL5 protein interacts with various signaling pathways and plays a role in controlling neurotransmitter release, synaptic plasticity, and cell survival. The CDKL5 protein has also been shown to regulate the activity of genes involved in neuronal development and the formation of synaptic connections.
Researchers are actively working to better understand the role of the CDKL5 protein in brain development and the underlying mechanisms of CDKL5 disorders. Further studies are needed to determine which proteins are targeted by the CDKL5 protein, as well as to develop effective treatments for individuals affected by CDKL5 disorders.
Mutations in the CDKL5 gene causeCDKL5 deficiency disorder.[7] CDKL5 deficiency disorder had, earlier, been thought of as a variant ofRett syndrome, due to some similarities in the clinical presentation.[8] CDKL5 deficiency syndrome is now known to be an independent clinical entity caused by mutations in a distinct X-linked gene, and is considered separate from Rett Syndrome, rather than a variant of it.[9] While CDKL5 is primarily found in girls, it has been seen in boys as well.[10] This disorder includes many of the features of classic Rett syndrome, including developmental problems, loss of language skills, and repeated hand-wringing or "hand-washing" movements), but also causes recurrent seizures, beginning in infancy. Some CDKL5 mutations alter a singleamino acid in a region of the CDKL5 protein that is critical for its kinase function. Other mutations lead to the production of an abnormally short, nonfunctioning version of the protein. At least 50 disease-causing mutations in this gene have been discovered.[11]
Further confirmation that CDKL5 is an independent disorder with its own characteristics is provided by a 2016 study which concluded that the clinical presentations of the two disorders were not identical.[12] At one time, mutations in the CDKL5 gene were thought to cause a disorder calledX-linked infantile spasm syndrome (ISSX),[13][14] orWest syndrome.[15][16] Studies have established CDKL5 disorder as a distinct clinical entity.
This section needs to beupdated. The reason given is:Ganaxolone is a recently-approved neurosteroid indicated for seizures associated with CDKL5 deficiency disorder.. Please help update this article to reflect recent events or newly available information.(March 2022)
The CDKL5 gene is located on the short (p) arm of the X chromosome at position 22.[26] More precisely, the CDKL5 gene is located from base pair 18,443,724 to base pair 18,671,748 on the X chromosome.[6]
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^Müller A, Helbig I, Jansen C, Bast T, Guerrini R, Jähn J, et al. (January 2016). "Retrospective evaluation of low long-term efficacy of antiepileptic drugs and ketogenic diet in 39 patients with CDKL5-related epilepsy".European Journal of Paediatric Neurology.20 (1):147–51.doi:10.1016/j.ejpn.2015.09.001.hdl:10067/1315500151162165141.PMID26387070.
^Montini E, Andolfi G, Caruso A, Buchner G, Walpole SM, Mariani M, Consalez G, Trump D, Ballabio A, Franco B (August 1998). "Identification and characterization of a novel serine-threonine kinase gene from the Xp22 region". (primary).Genomics.51 (3):427–33.doi:10.1006/geno.1998.5391.PMID9721213.
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