{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:37:16Z","timestamp":1790473036452,"version":"4.1.0"},"reference-count":56,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Clinica Chimica Acta"],"published-print":{"date-parts":[[2020,9]]},"DOI":"10.1016\/j.cca.2020.05.037","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T13:22:15Z","timestamp":1589980935000},"page":"287-294","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"special_numbering":"C","title":["Unusual double mutation in MECP2 and CDKL5 genes in Rett-like syndrome: Correlation with phenotype and genes expression"],"prefix":"10.1016","volume":"508","author":[{"given":"Marwa Ben","family":"Jdila","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chahnez Charfi","family":"Triki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania","family":"Ghorbel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafa","family":"Bouchalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihem Ben","family":"Ncir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma","family":"Kamoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiza","family":"Fakhfakh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cca.2020.05.037_b0005","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.cca.2016.06.003","article-title":"A novel CDKL5 mutation in a Japanese patient with atypical Rett syndrome","volume":"459","author":"Christianto","year":"2016","journal-title":"ClinicaChim. Acta"},{"issue":"2","key":"10.1016\/j.cca.2020.05.037_b0010","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1177\/1073858403260995","article-title":"Rett syndrome: a prototypical neurodevelopmental disorder","volume":"10","author":"Neul","year":"2004","journal-title":"The Neuroscientist"},{"issue":"3","key":"10.1016\/j.cca.2020.05.037_b0015","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1007\/s10803-013-1902-z","article-title":"Brief report: MECP2 mutations in people without Rett syndrome","volume":"44","author":"Suter","year":"2014","journal-title":"J. Autism Dev. Disord."},{"issue":"2","key":"10.1016\/j.cca.2020.05.037_b0020","doi-asserted-by":"crossref","DOI":"10.1098\/rsob.170216","article-title":"Rett syndrome: a neurological disorder with metabolic components","volume":"8","author":"Kyle","year":"2018","journal-title":"Open Biol."},{"issue":"3","key":"10.1016\/j.cca.2020.05.037_b0025","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1136\/jmedgenet-2015-103568","article-title":"Identification of novel genetic causes of Rett syndrome-like phenotypes","volume":"53","author":"Lopes","year":"2016","journal-title":"J. Med. Genet."},{"issue":"12","key":"10.1016\/j.cca.2020.05.037_b0030","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1002\/ccr3.2511","article-title":"Whole exome sequencing reveals a de novo missense variant in EEF1A2 in a Rett syndrome-like patient","volume":"7","author":"Kaur","year":"2019","journal-title":"Clin. Case Reports"},{"issue":"3","key":"10.1016\/j.cca.2020.05.037_b0035","article-title":"An early seizure variant type of a male Rett syndrome patient with a MECP2 p. Arg133His missense mutation","volume":"7","author":"Yoon","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"issue":"6","key":"10.1016\/j.cca.2020.05.037_b0040","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1136\/jmedgenet-2018-105775","article-title":"Genetic landscape of Rett syndrome-like phenotypes revealed by whole exome sequencing","volume":"56","author":"Iwama","year":"2019","journal-title":"J. Med. Genet."},{"key":"10.1016\/j.cca.2020.05.037_b0045","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ijdevneu.2019.01.005","article-title":"Surface-and voxel-based brain morphologic study in Rett and Rett-like syndrome with MECP2 mutation","volume":"73","author":"Shiohama","year":"2019","journal-title":"Int. J. Dev. Neurosci."},{"issue":"01","key":"10.1016\/j.cca.2020.05.037_b0050","first-page":"027","article-title":"CDKL5 in different atypical Rett syndrome variants: description of the first eight patients from Spain","volume":"1","author":"Mart\u00ednez","year":"2012","journal-title":"J. Pediat. Epilepsy"},{"key":"10.1016\/j.cca.2020.05.037_b0055","doi-asserted-by":"crossref","unstructured":"E. Frullanti F.T. Papa E. Grillo A. Clarke B. Ben-Zeev M. Pineda F. Mari Analysis of the Phenotypes in the Rett Networked Database Int. J. Genom. 2019.","DOI":"10.1155\/2019\/6956934"},{"issue":"16","key":"10.1016\/j.cca.2020.05.037_b0060","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.3390\/ijms20163925","article-title":"Genetic Landscape of Rett Syndrome Spectrum: Improvements and Challenges","volume":"20","author":"Vidal","year":"2019","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.cca.2020.05.037_b0065","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s13023-016-0499-7","article-title":"Rett syndrome: a wide clinical and autonomic picture","volume":"11","author":"Pini","year":"2016","journal-title":"Orphanet J. Rare Diseases"},{"issue":"1","key":"10.1016\/j.cca.2020.05.037_b0070","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.ajhg.2008.05.015","article-title":"FOXG1 is responsible for the congenital variant of Rett syndrome","volume":"83","author":"Ariani","year":"2008","journal-title":"Am. J. Human Genet."},{"issue":"2","key":"10.1016\/j.cca.2020.05.037_b0075","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1136\/jmg.2004.026237","article-title":"CDKL5\/STK9 is mutated in Rett syndrome variant with infantile spasms","volume":"42","author":"Scala","year":"2005","journal-title":"J. Med. Genet."},{"issue":"6","key":"10.1016\/j.cca.2020.05.037_b0080","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1086\/426462","article-title":"Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation","volume":"75","author":"Weaving","year":"2004","journal-title":"Am. J. Human Genet."},{"issue":"3","key":"10.1016\/j.cca.2020.05.037_b0085","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.nbd.2010.02.014","article-title":"CDKL5 is a brain MeCP2 target gene regulated by DNA methylation","volume":"38","author":"Carouge","year":"2010","journal-title":"Neurobiol. Disease"},{"issue":"14","key":"10.1016\/j.cca.2020.05.037_b0090","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1093\/hmg\/ddi198","article-title":"CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome","volume":"14","author":"Mari","year":"2005","journal-title":"Human Mol. Genet."},{"key":"10.1016\/j.cca.2020.05.037_b0095","first-page":"59","article-title":"Characterization of the Relationship of CDKL5 with MeCP2 and Dnmt1 in PrimaryRat Cortical Neurons","author":"Yi","year":"2016","journal-title":"Brazilian Arch. Biol. Technol."},{"issue":"17","key":"10.1016\/j.cca.2020.05.037_b0100","doi-asserted-by":"crossref","first-page":"8655","DOI":"10.1158\/0008-5472.CAN-06-1621","article-title":"N-myc is an essential downstream effector of Shh signaling during both normal and neoplastic cerebellar growth","volume":"66","author":"Hatton","year":"2006","journal-title":"Cancer Res."},{"issue":"11\u201312","key":"10.1016\/j.cca.2020.05.037_b0105","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.bbagrm.2012.08.001","article-title":"CDKL5, a novel MYCN-repressed gene, blocks cell cycle and promotes differentiation of neuronal cells","volume":"1819","author":"Valli","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA)-Gene Regulatory Mech."},{"issue":"4","key":"10.1016\/j.cca.2020.05.037_b0110","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.yebeh.2010.01.024","article-title":"Correlations between neurophysiological, behavioral, and cognitive function in Rett syndrome","volume":"17","author":"Vignoli","year":"2010","journal-title":"Epilepsy & Behav."},{"issue":"11","key":"10.1016\/j.cca.2020.05.037_b0115","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.1016\/j.ridd.2014.07.031","article-title":"Recent insights into genotype\u2013phenotype relationships in patients with Rett syndrome using a fine grain scale","volume":"35","author":"Fabio","year":"2014","journal-title":"Res. Develop. Disabilities"},{"key":"10.1016\/j.cca.2020.05.037_b0120","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cca.2017.08.001","article-title":"Novel mutations in the CDKL5 gene in complex genotypes associated with West syndrome with variable phenotype: First description of somatic mosaic state","volume":"473","author":"Jdila","year":"2017","journal-title":"Clin. Chim. Acta"},{"issue":"1","key":"10.1016\/j.cca.2020.05.037_b0125","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1089\/gtmb.2008.0076","article-title":"A novel MECP2 gene mutation in a Tunisian patient with Rett syndrome","volume":"13","author":"Fendri-Kriaa","year":"2009","journal-title":"Genetic Testing Mol. Biomarkers"},{"issue":"4","key":"10.1016\/j.cca.2020.05.037_b0130","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212 \u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"issue":"16","key":"10.1016\/j.cca.2020.05.037_b0135","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1093\/bioinformatics\/btv195","article-title":"PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels","volume":"31","author":"Choi","year":"2015","journal-title":"Bioinformatics"},{"issue":"1","key":"10.1016\/j.cca.2020.05.037_b0140","first-page":"7","article-title":"Predicting functional effect of human missense mutations using PolyPhen-2","volume":"76","author":"Adzhubei","year":"2013","journal-title":"Curr. Protocols Human Genet."},{"issue":"21","key":"10.1016\/j.cca.2020.05.037_b0145","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1093\/bioinformatics\/btp528","article-title":"Automated inference of molecular mechanisms of disease from amino acid substitutions","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"10.1016\/j.cca.2020.05.037_b0150","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.cca.2019.03.1609","article-title":"Homozygosity mapping and whole exome sequencing reveal a novel ERCC8 mutation in a Chinese consanguineous family with unique cerebellar ataxia","volume":"494","author":"Zhang","year":"2019","journal-title":"Clin. Chim. Acta"},{"issue":"1","key":"10.1016\/j.cca.2020.05.037_b0155","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1186\/s12887-018-1265-x","article-title":"NRG1 variant effects in patients with Hirschsprung disease","volume":"18","author":"Budi","year":"2018","journal-title":"BMC Pediat."},{"issue":"6","key":"10.1016\/j.cca.2020.05.037_b0160","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1017\/S1355838298980116","article-title":"Using reliability information to annotate RNA secondary structures","volume":"4","author":"Zuker","year":"1998","journal-title":"RNA"},{"issue":"17","key":"10.1016\/j.cca.2020.05.037_b0165","doi-asserted-by":"crossref","first-page":"3894","DOI":"10.1093\/nar\/gkf493","article-title":"Human non-synonymous SNPs: server and survey","volume":"30","author":"Ramensky","year":"2002","journal-title":"Nucleic Acids Res."},{"issue":"13","key":"10.1016\/j.cca.2020.05.037_b0170","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1177\/0883073815578529","article-title":"A Novel Mutation p. A59P in N-Terminal Domain of Methyl-CpG\u2013Binding Protein 2 Confers Phenotypic Variability in 3 Cases of Tunisian Rett Patients: Clinical Evaluations and In Silico Investigations","volume":"30","author":"Kharrat","year":"2015","journal-title":"J. Child Neurol."},{"issue":"8","key":"10.1016\/j.cca.2020.05.037_b0175","doi-asserted-by":"crossref","first-page":"2914","DOI":"10.1172\/JCI78167","article-title":"MECP2 disorders: from the clinic to mice and back","volume":"125","author":"Lombardi","year":"2015","journal-title":"J. Clin. Investig."},{"issue":"22","key":"10.1016\/j.cca.2020.05.037_b0180","doi-asserted-by":"crossref","first-page":"5593","DOI":"10.3390\/ijms20225593","article-title":"In silico study of rett syndrome treatment-related genes, mecp2, cdkl5, and foxg1, by evolutionary classification and disordered region assessment","volume":"20","author":"Fahmi","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.cca.2020.05.037_b0185","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3389\/fncel.2013.00064","article-title":"A novel DNA-binding feature of MeCP2 contributes to Rett syndrome","volume":"7","author":"Xu","year":"2013","journal-title":"Front. Cell. Neurosci."},{"issue":"3","key":"10.1016\/j.cca.2020.05.037_b0190","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1128\/MCB.01593-06","article-title":"Multiple modes of interaction between the methylated DNA binding protein MeCP2 and chromatin","volume":"27","author":"Nikitina","year":"2007","journal-title":"Mol. Cell. Biol."},{"issue":"22","key":"10.1016\/j.cca.2020.05.037_b0195","doi-asserted-by":"crossref","first-page":"7008","DOI":"10.1021\/bi990224y","article-title":"The methyl-CpG binding transcriptional repressor MeCP2 stably associates with nucleosomal DNA","volume":"38","author":"Chandler","year":"1999","journal-title":"Biochemistry"},{"issue":"2","key":"10.1016\/j.cca.2020.05.037_b0200","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00109-003-0497-9","article-title":"A WW domain binding region in methyl-CpG-binding protein MeCP2: impact on Rett syndrome","volume":"82","author":"Buschdorf","year":"2004","journal-title":"J. Mol. Med."},{"issue":"3","key":"10.1016\/j.cca.2020.05.037_b0205","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1136\/jmg.38.3.171","article-title":"MECP2 mutation in non-fatal, non-progressive encephalopathy in a male","volume":"38","author":"Imessaoudene","year":"2001","journal-title":"J. Med. Genet."},{"issue":"9","key":"10.1016\/j.cca.2020.05.037_b0210","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1093\/hmg\/10.9.941","article-title":"MECP2 is highly mutated in X-linked mental retardation","volume":"10","author":"Couvert","year":"2001","journal-title":"Hum. Mol. Genet."},{"issue":"1","key":"10.1016\/j.cca.2020.05.037_b0215","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/sj.ejhg.5200761","article-title":"Polymorphisms in the C-terminal domain of MECP2 in mentally handicapped boys: implications for genetic counselling","volume":"10","author":"Moncla","year":"2002","journal-title":"Eur. J. Human Genet."},{"issue":"5","key":"10.1016\/j.cca.2020.05.037_b0220","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1177\/0883073811420496","article-title":"Novel mutations in the C-terminal region of the MECP2 gene in Tunisian Rett syndrome patients","volume":"27","author":"Fendri-Kriaa","year":"2012","journal-title":"J. Child Neurol."},{"issue":"1","key":"10.1016\/j.cca.2020.05.037_b0225","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ejpn.2010.04.005","article-title":"Epilepsy caused by CDKL5 mutations","volume":"15","author":"Castr\u00e9n","year":"2011","journal-title":"Eur. J. Paediat. Neurol."},{"key":"10.1016\/j.cca.2020.05.037_b0230","doi-asserted-by":"crossref","DOI":"10.1016\/j.pediatrneurol.2019.02.015","article-title":"Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder: clinical review","author":"Olson","year":"2019","journal-title":"Pediatr. Neurol."},{"key":"10.1016\/j.cca.2020.05.037_b0235","doi-asserted-by":"crossref","unstructured":"J.A. Endicott, M.E. Noble, Structural characterization of the cyclin-dependent protein kinase family, 2013.","DOI":"10.1042\/BST20130097"},{"issue":"42","key":"10.1016\/j.cca.2020.05.037_b0240","first-page":"32048","article-title":"Functional consequences of mutations in CDKL5, an X-linked gene involved in infantile spasms and mental retardation","volume":"281","author":"Bertani","year":"2006","journal-title":"J. Biol. Chem."},{"issue":"3","key":"10.1016\/j.cca.2020.05.037_b0245","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1136\/jmg.2007.053504","article-title":"Impairment of CDKL5 nuclear localisation as a cause for severe infantile encephalopathy","volume":"45","author":"Rosas-Vargas","year":"2008","journal-title":"J. Med. Genet."},{"issue":"38","key":"10.1016\/j.cca.2020.05.037_b0250","doi-asserted-by":"crossref","first-page":"12777","DOI":"10.1523\/JNEUROSCI.1102-10.2010","article-title":"CDKL5, a protein associated with rett syndrome, regulates neuronal morphogenesis via Rac1 signaling","volume":"30","author":"Chen","year":"2010","journal-title":"J. Neurosci."},{"key":"10.1016\/j.cca.2020.05.037_b0255","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/728267","article-title":"What we know and would like to know about CDKL5 and its involvement in epileptic encephalopathy","author":"Kilstrup-Nielsen","year":"2012","journal-title":"Neural Plasticity"},{"issue":"30","key":"10.1016\/j.cca.2020.05.037_b0260","doi-asserted-by":"crossref","first-page":"21362","DOI":"10.1074\/jbc.M600504200","article-title":"Tumor necrosis factor-\u03b1 induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner","volume":"281","author":"Takeuchi","year":"2006","journal-title":"J. Biol. Chem."},{"issue":"1","key":"10.1016\/j.cca.2020.05.037_b0265","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/ana.21562","article-title":"Brain metabolism in Rett syndrome: age, clinical, and genotype correlations","volume":"65","author":"Horsk\u00e1","year":"2009","journal-title":"Ann. Neurol."},{"issue":"1","key":"10.1016\/j.cca.2020.05.037_b0270","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrn2038","article-title":"Microglia-mediated neurotoxicity: uncovering the molecular mechanisms","volume":"8","author":"Block","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"issue":"3","key":"10.1016\/j.cca.2020.05.037_b0275","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.neuroscience.2007.09.076","article-title":"Enhanced cell death in MeCP2 null cerebellar granule neurons exposed to excitotoxicity and hypoxia","volume":"150","author":"Russell","year":"2007","journal-title":"Neuroscience"},{"issue":"5","key":"10.1016\/j.cca.2020.05.037_b0280","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/gb-2003-4-5-111","article-title":"Genomic analysis of the eukaryotic protein kinase superfamily: a perspective","volume":"4","author":"Hanks","year":"2003","journal-title":"Genome Biol."}],"container-title":["Clinica Chimica Acta"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0009898120302412?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0009898120302412?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,14]],"date-time":"2025-09-14T14:57:36Z","timestamp":1757861856000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0009898120302412"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":56,"alternative-id":["S0009898120302412"],"URL":"https:\/\/doi.org\/10.1016\/j.cca.2020.05.037","relation":{},"ISSN":["0009-8981"],"issn-type":[{"value":"0009-8981","type":"print"}],"subject":[],"published":{"date-parts":[[2020,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Unusual double mutation in MECP2 and CDKL5 genes in Rett-like syndrome: Correlation with phenotype and genes expression","name":"articletitle","label":"Article Title"},{"value":"Clinica Chimica Acta","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cca.2020.05.037","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}