{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:30:09Z","timestamp":1787502609033,"version":"build-2736575974"},"reference-count":109,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T00:00:00Z","timestamp":1692489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KAKENHI","award":["21K07293"],"award-info":[{"award-number":["21K07293"]}]},{"name":"KAKENHI","award":["23H02575"],"award-info":[{"award-number":["23H02575"]}]},{"name":"KAKENHI","award":["21H05685"],"award-info":[{"award-number":["21H05685"]}]},{"name":"KAKENHI","award":["23H04227"],"award-info":[{"award-number":["23H04227"]}]},{"name":"Grant-in-Aid for Transformative Research Areas (A)","award":["21K07293"],"award-info":[{"award-number":["21K07293"]}]},{"name":"Grant-in-Aid for Transformative Research Areas (A)","award":["23H02575"],"award-info":[{"award-number":["23H02575"]}]},{"name":"Grant-in-Aid for Transformative Research Areas (A)","award":["21H05685"],"award-info":[{"award-number":["21H05685"]}]},{"name":"Grant-in-Aid for Transformative Research Areas (A)","award":["23H04227"],"award-info":[{"award-number":["23H04227"]}]},{"name":"Japan Epilepsy Research Foundation","award":["21K07293"],"award-info":[{"award-number":["21K07293"]}]},{"name":"Japan Epilepsy Research Foundation","award":["23H02575"],"award-info":[{"award-number":["23H02575"]}]},{"name":"Japan Epilepsy Research Foundation","award":["21H05685"],"award-info":[{"award-number":["21H05685"]}]},{"name":"Japan Epilepsy Research Foundation","award":["23H04227"],"award-info":[{"award-number":["23H04227"]}]},{"name":"Takeda Science Foundation","award":["21K07293"],"award-info":[{"award-number":["21K07293"]}]},{"name":"Takeda Science Foundation","award":["23H02575"],"award-info":[{"award-number":["23H02575"]}]},{"name":"Takeda Science Foundation","award":["21H05685"],"award-info":[{"award-number":["21H05685"]}]},{"name":"Takeda Science Foundation","award":["23H04227"],"award-info":[{"award-number":["23H04227"]}]},{"name":"Naito Foundation","award":["21K07293"],"award-info":[{"award-number":["21K07293"]}]},{"name":"Naito Foundation","award":["23H02575"],"award-info":[{"award-number":["23H02575"]}]},{"name":"Naito Foundation","award":["21H05685"],"award-info":[{"award-number":["21H05685"]}]},{"name":"Naito Foundation","award":["23H04227"],"award-info":[{"award-number":["23H04227"]}]},{"name":"Hokuto Foundation","award":["21K07293"],"award-info":[{"award-number":["21K07293"]}]},{"name":"Hokuto Foundation","award":["23H02575"],"award-info":[{"award-number":["23H02575"]}]},{"name":"Hokuto Foundation","award":["21H05685"],"award-info":[{"award-number":["21H05685"]}]},{"name":"Hokuto Foundation","award":["23H04227"],"award-info":[{"award-number":["23H04227"]}]},{"name":"Mochida Memorial Foundation for Medical and Pharmaceutical Research","award":["21K07293"],"award-info":[{"award-number":["21K07293"]}]},{"name":"Mochida Memorial Foundation for Medical and Pharmaceutical Research","award":["23H02575"],"award-info":[{"award-number":["23H02575"]}]},{"name":"Mochida Memorial Foundation for Medical and Pharmaceutical Research","award":["21H05685"],"award-info":[{"award-number":["21H05685"]}]},{"name":"Mochida Memorial Foundation for Medical and Pharmaceutical Research","award":["23H04227"],"award-info":[{"award-number":["23H04227"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>CASK-related disorders are a form of rare X-linked neurological diseases and most of the patients are females. They are characterized by several symptoms, including microcephaly with pontine and cerebellar hypoplasia (MICPCH), epilepsy, congenital nystagmus, and neurodevelopmental disorders. Whole-genome sequencing has identified various mutations, including nonsense and missense mutations, from patients with CASK-related disorders, revealing correlations between specific mutations and clinical phenotypes. Notably, missense mutations associated with epilepsy and intellectual disability were found throughout the whole region of the CASK protein, while missense mutations related to microcephaly and MICPCH were restricted in certain domains. To investigate the pathophysiology of CASK-related disorders, research groups have employed diverse methods, including the generation of CASK knockout mice and the supplementation of CASK to rescue the phenotypes. These approaches have yielded valuable insights into the identification of functional domains of the CASK protein associated with a specific phenotype. Additionally, recent advancements in the AI-based prediction of protein structure, such as AlphaFold2, and the application of genome-editing techniques to generate CASK mutant mice carrying missense mutations from patients with CASK-related disorders, allow us to understand the pathophysiology of CASK-related disorders in more depth and to develop novel therapeutic methods for the fundamental treatment of CASK-related disorders.<\/jats:p>","DOI":"10.3390\/genes14081656","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T01:38:31Z","timestamp":1692581911000},"page":"1656","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Diverse Clinical Phenotypes of CASK-Related Disorders and Multiple Functional Domains of CASK Protein"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4195-2804","authenticated-orcid":false,"given":"Takuma","family":"Mori","sequence":"first","affiliation":[{"name":"Department of Neuroinnovation, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto 390-8621, Japan"},{"name":"Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1673-4637","authenticated-orcid":false,"given":"Katsuhiko","family":"Tabuchi","sequence":"additional","affiliation":[{"name":"Department of Neuroinnovation, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto 390-8621, Japan"},{"name":"Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1083\/jcb.142.1.129","article-title":"Human CASK\/LIN-2 binds syndecan-2 and protein 4.1 and localizes to the basolateral membrane of epithelial cells","volume":"142","author":"Cohen","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1006\/geno.1998.5404","article-title":"The location of human CASK at Xp11.4 identifies this gene as a candidate for X-linked optic atrophy","volume":"51","author":"Dimitratos","year":"1998","journal-title":"Genomics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1002\/humu.20564","article-title":"Detection of genomic copy number changes in patients with idiopathic mental retardation by high-resolution X-array-CGH: Important role for increased gene dosage of XLMR genes","volume":"28","author":"Froyen","year":"2007","journal-title":"Hum. Mutat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1038\/ng.194","article-title":"Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum","volume":"40","author":"Najm","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1750-1172-7-18","article-title":"Spectrum of pontocerebellar hypoplasia in 13 girls and boys with CASK mutations: Confirmation of a recognizable phenotype and first description of a male mosaic patient","volume":"7","author":"Burglen","year":"2012","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1111\/j.1528-1167.2012.03548.x","article-title":"CASK aberrations in male patients with Ohtahara syndrome and cerebellar hypoplasia","volume":"53","author":"Saitsu","year":"2012","journal-title":"Epilepsia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.1002\/ajmg.a.35640","article-title":"Clinical and radiological features of Japanese patients with a severe phenotype due to CASK mutations","volume":"158A","author":"Takanashi","year":"2012","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.braindev.2013.03.007","article-title":"A de novo CASK mutation in pontocerebellar hypoplasia type 3 with early myoclonic epilepsy and tetralogy of Fallot","volume":"36","author":"Nakamura","year":"2014","journal-title":"Brain Dev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.braindev.2015.02.007","article-title":"Late-onset epileptic spasms in a female patient with a CASK mutation","volume":"37","author":"Nakajiri","year":"2015","journal-title":"Brain Dev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ejpn.2021.02.006","article-title":"CASK related disorder: Epilepsy and developmental outcome","volume":"31","author":"Giacomini","year":"2021","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1136\/jmedgenet-2011-100218","article-title":"Phenotypic spectrum associated with CASK loss-of-function mutations","volume":"48","author":"Moog","year":"2011","journal-title":"J. Med. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ajhg.2008.12.018","article-title":"A missense mutation in CASK causes FG syndrome in an Italian family","volume":"84","author":"Piluso","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/ajmg.a.38069","article-title":"A de novo splice site mutation in CASK causes FG syndrome-4 and congenital nystagmus","volume":"173","author":"Dunn","year":"2017","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/ejhg.2009.220","article-title":"CASK mutations are frequent in males and cause X-linked nystagmus and variable XLMR phenotypes","volume":"18","author":"Hackett","year":"2010","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41398-020-00994-0","article-title":"Presynaptic dysfunction in CASK-related neurodevelopmental disorders","volume":"10","author":"Becker","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1161\/CIRCRESAHA.120.318170","article-title":"Loss of CASK Accelerates Heart Failure Development","volume":"128","author":"Mustroph","year":"2021","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9185","DOI":"10.1007\/s13277-014-2179-3","article-title":"High expression of CASK correlates with progression and poor prognosis of colorectal cancer","volume":"35","author":"Wei","year":"2014","journal-title":"Tumor Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11631","DOI":"10.18632\/oncotarget.2600","article-title":"Down-regulation of miR-203 induced by Helicobacter pylori infection promotes the proliferation and invasion of gastric cancer by targeting CASK","volume":"5","author":"Zhou","year":"2014","journal-title":"Oncotarget"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"681683","DOI":"10.3389\/fonc.2021.681683","article-title":"CASK Silence Overcomes Sorafenib Resistance of Hepatocellular Carcinoma through Activating Apoptosis and Autophagic Cell Death","volume":"11","author":"Ding","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"108789","DOI":"10.1016\/j.abb.2021.108789","article-title":"CASK regulates Notch pathway and functions as a tumor promoter in pancreatic cancer","volume":"701","author":"Qu","year":"2021","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1523\/JNEUROSCI.16-08-02488.1996","article-title":"CASK: A novel dlg\/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexins","volume":"16","author":"Hata","year":"1996","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1042\/bj3200694","article-title":"Caenorhabditis elegans LIN-2A and mammalian neuronal CASK are prototypical members of a subfamily of MAGUKs (membrane-associated guanylate kinases) characterized by a common kinase-like domain and a guanylate kinase domain predicted to bind ATP","volume":"320","author":"Baines","year":"1996","journal-title":"Biochem. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0925-4773(97)00668-0","article-title":"Camguk, Lin-2, and CASK: Novel membrane-associated guanylate kinase homologs that also contain CaM kinase domains","volume":"63","author":"Dimitratos","year":"1997","journal-title":"Mech. Dev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.cell.2008.02.036","article-title":"CASK Functions as a Mg2+-independent neurexin kinase","volume":"133","author":"Mukherjee","year":"2008","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.molcel.2011.07.021","article-title":"Liprin-mediated large signaling complex organization revealed by the liprin-\u03b1\/CASK and liprin-\u03b1\/liprin-\u03b2 complex structures","volume":"43","author":"Wei","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1083\/jcb.201301011","article-title":"Liprin-\u03b12 promotes the presynaptic recruitment and turnover of RIM1\/CASK to facilitate synaptic transmission","volume":"201","author":"Spangler","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"19051","DOI":"10.1074\/jbc.M400284200","article-title":"A multiprotein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is associated with inward rectifier Kir2 potassium channels","volume":"279","author":"Leonoudakis","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.bbrc.2006.10.113","article-title":"CASK associates with glutamate receptor interacting protein and signaling molecules","volume":"351","author":"Hong","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jmb.2011.07.005","article-title":"The molecular basis of the Caskin1 and Mint1 interaction with CASK","volume":"412","author":"Stafford","year":"2011","journal-title":"J. Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1128\/MCB.22.6.1778-1791.2002","article-title":"A novel and conserved protein-protein interaction domain of mammalian Lin-2\/CASK binds and recruits SAP97 to the lateral surface of epithelia","volume":"22","author":"Lee","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/nn.2362","article-title":"SAP97 and CASK mediate sorting of NMDA receptors through a previously unknown secretory pathway","volume":"12","author":"Jeyifous","year":"2009","journal-title":"Nat. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"C183","DOI":"10.1152\/ajpcell.00249.2001","article-title":"Basolateral membrane expression of the Kir 2.3 channel is coordinated by PDZ interaction with Lin-7\/CASK complex","volume":"282","author":"Olsen","year":"2002","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"C1733","DOI":"10.1152\/ajpcell.00323.2007","article-title":"Lin-7 targets the Kir 2.3 channel on the basolateral membrane via a L27 domain interaction with CASK","volume":"293","author":"Alewine","year":"2007","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1083\/jcb.142.1.139","article-title":"Direct interaction of CASK\/LIN-2 and syndecan heparan sulfate proteoglycan and their overlapping distribution in neuronal synapses","volume":"142","author":"Hsueh","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.1523\/JNEUROSCI.19-17-07415.1999","article-title":"Regulated expression and subcellular localization of syndecan heparan sulfate proteoglycans and the syndecan-binding protein CASK\/LIN-2 during rat brain development","volume":"19","author":"Hsueh","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41583-020-00415-7","article-title":"Neurexins: Molecular codes for shaping neuronal synapses","volume":"22","author":"Gomez","year":"2021","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"24453","DOI":"10.1074\/jbc.274.35.24453","article-title":"Association of neuronal calcium channels with modular adaptor proteins","volume":"274","author":"Maximov","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6939","DOI":"10.1523\/JNEUROSCI.22-16-06939.2002","article-title":"Synaptic targeting of N-type calcium channels in hippocampal neurons","volume":"22","author":"Maximov","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/35005118","article-title":"Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK\/LIN-2","volume":"404","author":"Hsueh","year":"2000","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0896-6273(04)00139-4","article-title":"Transcriptional modification by a CASK-interacting nucleosome assembly protein","volume":"42","author":"Wang","year":"2004","journal-title":"Neuron"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/cne.20825","article-title":"Neural activity- and development-dependent expression and distribution of CASK interacting nucleosome assembly protein in mouse brain","volume":"494","author":"Lin","year":"2006","journal-title":"J. Comp. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0304-3835(01)00846-1","article-title":"CASK and its target gene Reelin were co-upregulated in human esophageal carcinoma","volume":"179","author":"Wang","year":"2002","journal-title":"Cancer Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.bbrc.2009.03.015","article-title":"CASK point mutation regulates protein-protein interactions and NR2b promoter activity","volume":"382","author":"Huang","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41592-022-01488-1","article-title":"ColabFold: Making protein folding accessible to all","volume":"19","author":"Mirdita","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1111\/jnc.15215","article-title":"Missense mutations in CASK, coding for the calcium-\/calmodulin-dependent serine protein kinase, interfere with neurexin binding and neurexin-induced oligomerization","volume":"157","author":"Pan","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D980","DOI":"10.1093\/nar\/gkt1113","article-title":"ClinVar: Public archive of relationships among sequence variation and human phenotype","volume":"42","author":"Landrum","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1002\/ajmg.a.32433","article-title":"The CASK gene harbored in a deletion detected by array-CGH as a potential candidate for a gene causative of X-linked dominant mental retardation","volume":"146A","author":"Hayashi","year":"2008","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/ng.367","article-title":"A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation","volume":"41","author":"Tarpey","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00439-011-1047-0","article-title":"Novel intragenic duplications and mutations of CASK in patients with mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH)","volume":"131","author":"Hayashi","year":"2012","journal-title":"Hum. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e199","DOI":"10.1093\/brain\/awr108","article-title":"Mutations of TSEN and CASK genes are prevalent in pontocerebellar hypoplasias type 2 and 4","volume":"135","author":"Valayannopoulos","year":"2012","journal-title":"Brain"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4846","DOI":"10.1093\/hmg\/ddu199","article-title":"The genetic landscape of infantile spasms","volume":"23","author":"Michaud","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13023-015-0256-3","article-title":"Phenotypic and molecular insights into CASK-related disorders in males","volume":"10","author":"Moog","year":"2015","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Rump, P., Jazayeri, O., van Dijk-Bos, K.K., Johansson, L.F., van Essen, A.J., Verheij, J.B., Veenstra-Knol, H.E., Redeker, E.J., Mannens, M.M., and Swertz, M.A. (2016). Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly. BMC Med. Genom., 9.","DOI":"10.1186\/s12920-016-0167-8"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"529","DOI":"10.4067\/S0370-41062017000400014","article-title":"Pontocerebellar hypoplasia secondary to CASK gene deletion: Case report","volume":"88","author":"Rivas","year":"2017","journal-title":"Rev. Chil. Pediatr."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hayashi, S., Uehara, D.T., Tanimoto, K., Mizuno, S., Chinen, Y., Fukumura, S., Takanashi, J.I., Osaka, H., Okamoto, N., and Inazawa, J. (2017). Comprehensive investigation of CASK mutations and other genetic etiologies in 41 patients with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH). PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181791"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1038\/s41431-017-0022-1","article-title":"Exome Pool-Seq in neurodevelopmental disorders","volume":"25","author":"Popp","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"DeLuca, S.C., Wallace, D.A., Trucks, M.R., and Mukherjee, K. (2017). A clinical series using intensive neurorehabilitation to promote functional motor and cognitive skills in three girls with CASK mutation. BMC Res. Notes, 10.","DOI":"10.1186\/s13104-017-3065-z"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"177","DOI":"10.5582\/irdr.2017.01031","article-title":"A novel CASK mutation identified in siblings exhibiting developmental disorders with\/without microcephaly","volume":"6","author":"Seto","year":"2017","journal-title":"Intractable Rare Dis. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1089\/omi.2017.0009","article-title":"Next-Generation Sequencing Reveals Novel Mutations in X-linked Intellectual Disability","volume":"21","author":"Muthusamy","year":"2017","journal-title":"OMICS"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1002\/ajmg.a.40429","article-title":"A de novo in-frame deletion of CASK gene causes early onset infantile spasms and supratentorial cerebral malformation in a female patient","volume":"176","author":"Bozarth","year":"2018","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s00439-018-1874-3","article-title":"Two microcephaly-associated novel missense mutations in CASK specifically disrupt the CASK-neurexin interaction","volume":"137","author":"LaConte","year":"2018","journal-title":"Hum. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1002\/ajmg.a.60687","article-title":"An N-terminal heterozygous missense CASK mutation is associated with microcephaly and bilateral retinal dystrophy plus optic nerve atrophy","volume":"179","author":"LaConte","year":"2019","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1002\/humu.23536","article-title":"Novel CASK mutations in cases with syndromic microcephaly","volume":"39","author":"Cristofoli","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/gim.2017.159","article-title":"Clinical relevance of systematic phenotyping and exome sequencing in patients with short stature","volume":"20","author":"Hauer","year":"2018","journal-title":"Genet. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41439-019-0051-0","article-title":"Discordant phenotype caused by CASK mutation in siblings with NF1","volume":"6","author":"Murakami","year":"2019","journal-title":"Hum. Genome Var."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1093\/abbs\/gmz052","article-title":"PPAR-\u03b3 activation increases insulin secretion independent of CASK in INS-1 cells","volume":"51","author":"Zhang","year":"2019","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1002\/humu.23822","article-title":"Characterization of intellectual disability and autism comorbidity through gene panel sequencing","volume":"40","author":"Aspromonte","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/epi.16427","article-title":"Genetic diagnoses in epilepsy: The impact of dynamic exome analysis in a pediatric cohort","volume":"61","author":"Rochtus","year":"2020","journal-title":"Epilepsia"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Ibarluzea, N., Hoz, A.B., Villate, O., Llano, I., Ocio, I., Mart\u00ed, I., Guitart, M., Gabau, E., Andrade, F., and Gener, B. (2020). Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability. Genes, 11.","DOI":"10.3390\/genes11010051"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.2147\/IJGM.S300775","article-title":"Whole-Exome Sequencing for Identifying Genetic Causes of Intellectual Developmental Disorders","volume":"14","author":"Guo","year":"2021","journal-title":"Int. J. Gen. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1002\/ajmg.a.62863","article-title":"Pathogenic variants in CASK: Expanding the genotype-phenotype correlations","volume":"188","author":"Dubbs","year":"2022","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"856636","DOI":"10.3389\/fgene.2022.856636","article-title":"Case report: A novel CASK mutation in a Chinese female child with microcephaly with pontine and cerebellar hypoplasia","volume":"13","author":"Xie","year":"2022","journal-title":"Front. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"933785","DOI":"10.3389\/fgene.2022.933785","article-title":"Case Report: Identification of a novel CASK missense variant in a Chinese family with MICPCH","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Genet."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Wu, S., Jiang, C., Li, J., Zhang, G., Shen, Y., and Wang, J. (2022). A novel missense variant in the CASK gene causes intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia. BMC Med. Genom., 15.","DOI":"10.1186\/s12920-022-01275-z"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13052-022-01248-z","article-title":"A de novo variant in CASK gene causing intellectual disability and brain hypoplasia: A case report and literature review","volume":"48","author":"Zhang","year":"2022","journal-title":"Ital. J. Pediatr."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e2065","DOI":"10.1002\/mgg3.2065","article-title":"Two heterozygous mutations in the calcium\/calmodulin-dependent serine protein kinase gene (CASK) in cases with developmental disorders","volume":"10","author":"Yang","year":"2022","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1136\/jmedgenet-2021-108115","article-title":"Complete loss of the X-linked gene CASK causes severe cerebellar degeneration","volume":"59","author":"Patel","year":"2022","journal-title":"J. Med. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1093\/brain\/awac117","article-title":"Somatic variants in diverse genes leads to a spectrum of focal cortical malformations","volume":"145","author":"Lai","year":"2022","journal-title":"Brain"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e202201512","DOI":"10.26508\/lsa.202201512","article-title":"Regulation of Liprin-\u03b1 phase separation by CASK is disrupted by a mutation in its CaM kinase domain","volume":"5","author":"Tibbe","year":"2022","journal-title":"Life Sci. Alliance"},{"key":"ref_82","first-page":"517","article-title":"Mosaicism of a Truncating Variant of CASK Causes Congenital Heart Disease and Neurodevelopmental Disorder","volume":"13","author":"Yokoi","year":"2023","journal-title":"Mol. Syndromol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"505","DOI":"10.3389\/fneur.2019.00505","article-title":"The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children","volume":"10","author":"Long","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nature13908","article-title":"The contribution of de novo coding mutations to autism spectrum disorder","volume":"515","author":"Iossifov","year":"2014","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"(2017). Deciphering Developmental Disorders Study. Prevalence and architecture of de novo mutations in developmental disorders. Nature, 542, 433\u2013438.","DOI":"10.1038\/nature21062"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1126\/science.1146221","article-title":"A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice","volume":"318","author":"Tabuchi","year":"2007","journal-title":"Science"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ng1136","article-title":"Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism","volume":"34","author":"Jamain","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.ajhg.2015.02.013","article-title":"De novo mutations in SIK1 cause a spectrum of developmental epilepsies","volume":"96","author":"Hansen","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"706494","DOI":"10.3389\/fnmol.2021.706494","article-title":"Risperidone Mitigates Enhanced Excitatory Neuronal Function and Repetitive Behavior Caused by an ASD-Associated Mutation of SIK1","volume":"14","author":"Badawi","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/351325a0","article-title":"Characterization of a murine gene expressed from the inactive X chromosome","volume":"351","author":"Borsani","year":"1991","journal-title":"Nature"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/nrg1604","article-title":"X-chromosome inactivation: A hypothesis linking ontogeny and phylogeny","volume":"6","author":"Huynh","year":"2005","journal-title":"Nat. Rev. Genet."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/s41380-018-0338-4","article-title":"Deficiency of calcium\/calmodulin-dependent serine protein kinase disrupts the excitatory-inhibitory balance of synapses by down-regulating GluN2B","volume":"24","author":"Mori","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/nrm4063","article-title":"Nonsense-mediated mRNA decay: An intricate machinery that shapes transcriptomes","volume":"16","author":"Jensen","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s40478-016-0295-6","article-title":"X-linked intellectual disability gene CASK regulates postnatal brain growth in a non-cell autonomous manner","volume":"4","author":"Srivastava","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Guo, Q., Kouyama-Suzuki, E., Shirai, Y., Cao, X., Yanagawa, T., Mori, T., and Tabuchi, K. (2023). Structural Analysis Implicates CASK-Liprin-\u03b12 Interaction in Cerebellar Granular Cell Death in MICPCH Syndrome. Cells, 12.","DOI":"10.3390\/cells12081177"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"110624","DOI":"10.1016\/j.celrep.2022.110624","article-title":"Neurexins play a crucial role in cerebellar granule cell survival by organizing autocrine machinery for neurotrophins","volume":"39","author":"Uemura","year":"2022","journal-title":"Cell Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1097\/00001756-200411150-00015","article-title":"Differential expression patterns of TrkB ligands in the macaque monkey brain","volume":"15","author":"Mori","year":"2004","journal-title":"Neuroreport"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0896-6273(00)80938-1","article-title":"Abnormal cerebellar development and foliation in BDNF\u2212\/\u2212 mice reveals a role for neurotrophins in CNS patterning","volume":"19","author":"Schwartz","year":"1997","journal-title":"Neuron"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1242\/dev.129.6.1435","article-title":"BDNF stimulates migration of cerebellar granule cells","volume":"129","author":"Borghesani","year":"2002","journal-title":"Development"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1007\/s00018-016-2183-4","article-title":"CASK stabilizes neurexin and links it to liprin-\u03b1 in a neuronal activity-dependent manner","volume":"73","author":"LaConte","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/ana.24073","article-title":"GRIN2B mutations in West syndrome and intellectual disability with focal epilepsy","volume":"75","author":"Lemke","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1136\/jmedgenet-2016-104509","article-title":"encephalopathy: Novel findings on phenotype, variant clustering, functional consequences and treatment aspects","volume":"54","author":"Platzer","year":"2017","journal-title":"J. Med. Genet."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.eplepsyres.2015.09.014","article-title":"Development of a mouse model of infantile spasms induced by N-methyl-D-aspartate","volume":"118","author":"Shi","year":"2015","journal-title":"Epilepsy Res."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Pang, B., Mori, T., Badawi, M., Zhou, M., Guo, Q., Suzuki-Kouyama, E., Yanagawa, T., Shirai, Y., and Tabuchi, K. (2022). An Epilepsy-Associated Mutation of Salt-Inducible Kinase 1 Increases the Susceptibility to Epileptic Seizures and Interferes with Adrenocorticotropic Hormone Therapy for Infantile Spasms in Mice. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147927"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/ana.21082","article-title":"Model of infantile spasms induced by N-methyl-D-aspartic acid in prenatally impaired brain","volume":"61","author":"Jehle","year":"2007","journal-title":"Ann. Neurol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1073\/pnas.0611003104","article-title":"Deletion of CASK in mice is lethal and impairs synaptic function","volume":"104","author":"Atasoy","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/dmcn.15419","article-title":"Expanding the natural history of CASK-related disorders to the prenatal period","volume":"65","author":"Gafner","year":"2023","journal-title":"Dev. Med. Child. Neurol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"a009886","DOI":"10.1101\/cshperspect.a009886","article-title":"Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities","volume":"4","author":"Zoghbi","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Depienne, C., Bouteiller, D., Keren, B., Cheuret, E., Poirier, K., Trouillard, O., Benyahia, B., Quelin, C., Carpentier, W., and Julia, S. (2009). Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. PLoS Genet., 5.","DOI":"10.1371\/annotation\/314060d5-06da-46e0-b9e4-57194e8ece3a"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/8\/1656\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:37:52Z","timestamp":1760128672000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/8\/1656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,20]]},"references-count":109,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["genes14081656"],"URL":"https:\/\/doi.org\/10.3390\/genes14081656","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,20]]}}}