A novel CDKL5 mutation in a Japanese patient with atypical Rett syndrome

Christianto, Antonius; Katayama, Syouichi; Kameshita, Isamu; Inazu, Toshiyuki

doi:10.1016/j.cca.2016.06.003

Cited by 11 publications

(11 citation statements)

References 31 publications

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“…As CDKL5 plays many important roles in the nervous system, gene mutations leading to the loss of its activity are also believed to lead to the onset of severe neurological diseases. In practice, several pathogenic CDKL5 variants exhibit reduced or absence of phosphorylation activity [25,41,44]. Consequently, the identification of CDKL5 substrates is an important prerequisite for the discovery of drug targets.…”

Section: Discussionmentioning

confidence: 99%

“…The relationship between CDKL5 and neurodevelopmental disorders has been the subject of many reports. In particular, missense mutations in the sequence encoding the catalytic domain of CDKL5 are thought to induce CDD by causing a decline or complete loss of the enzyme function [25,40,41]. Consequently, exploration of the CDKL5 substrates and analysis of the biological significance of their phosphorylation will deepen our understanding of the pathology of CDD, potentially yielding significant clues for future treatment possibilities.…”

Section: Possible Targets Of Cdkl5mentioning

confidence: 99%

“…In particular, recent advancements in the next-generation sequencing technology have enabled highly efficient identification of mutations, and mutation databases such as the Genome Aggregation Database (gnomAD) (http://gnomad.broadinstitute.org/) and the ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) have been populated with many examples of such mutations [93,94]. We have identified a novel CDKL5 mutation, resulting in Y177C substitution, in a Japanese patient, and showed that 6 Neural Plasticity it results in a complete loss of the CDKL5 enzymatic activity [25]. Nevertheless, little is known regarding the manner in which the CDKL5 modification affects the activity.…”

Section: Pathogenic Substitutions In the Kinase Domain Of Cdkl5mentioning

confidence: 99%

“…From 2004 onwards, reports of CDKL5 as the causative gene of atypical Rett syndrome began to emerge [7]. Many new mutations have been discovered in patients with CDD so far; both missense and nonsense mutations in the CDKL5 gene have been reported [21][22][23][24][25]. As most of the missense mutations occur in the region encoding the catalytic domain of CDKL5, it is believed that reduced activity of the enzyme-specifically, its ability to modify amino acid residues-is the direct cause of the onset of disease.…”

Section: Introductionmentioning

confidence: 99%

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Cyclin-Dependent Kinase-Like 5 (CDKL5): Possible Cellular Signalling Targets and Involvement in CDKL5 Deficiency Disorder

et al. 2020

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Cyclin-dependent kinase-like 5 (CDKL5, also known as STK9) is a serine/threonine protein kinase originally identified in 1998 during a transcriptional mapping project of the human X chromosome. Thereafter, a mutation in CDKL5 was reported in individuals with the atypical Rett syndrome, a neurodevelopmental disorder, suggesting that CDKL5 plays an important regulatory role in neuronal function. The disease associated with CDKL5 mutation has recently been recognised as CDKL5 deficiency disorder (CDD) and has been distinguished from the Rett syndrome owing to its symptomatic manifestation. Because CDKL5 mutations identified in patients with CDD cause enzymatic loss of function, CDKL5 catalytic activity is likely strongly associated with the disease. Consequently, the exploration of CDKL5 substrate characteristics and regulatory mechanisms of its catalytic activity are important for identifying therapeutic target molecules and developing new treatment. In this review, we summarise recent findings on the phosphorylation of CDKL5 substrates and the mechanisms of CDKL5 phosphorylation and dephosphorylation. We also discuss the relationship between changes in the phosphorylation signalling pathways and the Cdkl5 knockout mouse phenotype and consider future prospects for the treatment of mental and neurological disease associated with CDKL5 mutations.

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Section: Discussionmentioning

confidence: 99%

Section: Possible Targets Of Cdkl5mentioning

confidence: 99%

Section: Pathogenic Substitutions In the Kinase Domain Of Cdkl5mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cyclin-Dependent Kinase-Like 5 (CDKL5): Possible Cellular Signalling Targets and Involvement in CDKL5 Deficiency Disorder

et al. 2020

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“…Therefore, 28 articles were eligible for full-text review and data assessment. Finally, 15 articles were excluded due to unavailable data for constructing a 2 × 2 contingency table, and the remaining 13 studies were enrolled in the meta-analysis [28-40]. A flowchart demonstrating the study selection process is illustrated in Fig.…”

Section: Resultsmentioning

confidence: 99%

A Meta-Analysis of the Diagnostic Accuracy of Circular RNAs in Digestive System Malignancy

Chen¹,

Zhang²,

Han³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have been found to be dysregulated in various cancers. However, the clinical application value of these circRNAs in digestive system cancers remains to be clarified. We aimed to comprehensively explore the potential role of circRNAs as diagnostic indicators in digestive system malignancies. Methods: Relevant studies were systematically retrieved from PubMed, Web of Science and the Cochrane Library. The data that were required to complete 2 × 2 contingency tables were obtained from the included studies. Stratified analyses by cancer type, sample size and publication year were performed. Results: Thirteen studies with 2,276 individuals were included in the meta-analysis. The pooled sensitivity and specificity of circRNAs in the diagnosis of digestive system malignancy were 0.72 [95% confidence interval (CI): 0.65-0.77] and 0.77 (95% CI: 0.72-0.81), respectively. The overall positive likelihood ratio was 3.09 (95% CI: 2.64-3.62), and the overall negative likelihood ratio was 0.37 (95% CI: 0.31-0.44). The pooled diagnostic odds ratio was 8.38 (95% CI: 6.86-10.25), and the overall area under the curve was 0.81 (95% CI: 0.77-0.84), indicating good discriminative ability of circRNAs as biomarkers for digestive system malignancy. Conclusion: circRNAs distinguish patients with digestive system cancer from controls with relatively high diagnostic accuracy. circRNAs may be used as potential biomarkers for the diagnosis of digestive system malignancy.

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Straightforward and rapid method for detection of cyclin-dependent kinase-like 5 activity

Katayama

Inazu

2019

Analytical Biochemistry

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A novel CDKL5 mutation in a Japanese patient with atypical Rett syndrome

Cited by 11 publications

References 31 publications

Cyclin-Dependent Kinase-Like 5 (CDKL5): Possible Cellular Signalling Targets and Involvement in CDKL5 Deficiency Disorder

Cyclin-Dependent Kinase-Like 5 (CDKL5): Possible Cellular Signalling Targets and Involvement in CDKL5 Deficiency Disorder

A Meta-Analysis of the Diagnostic Accuracy of Circular RNAs in Digestive System Malignancy

Straightforward and rapid method for detection of cyclin-dependent kinase-like 5 activity

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