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X\u2010linked intellectual disability (XLID) is a subset of these disorders caused by genetic defects on the X chromosome, affecting about 2 out of 1,000 males. In syndromic form, it leads to a broad range of cognitive, behavioral, ocular, and physical disabilities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Employing exome or genome sequencing, here we identified 4 missense variants (c.475C\u2009&gt;\u2009G; p.H159D, c.1373C\u2009&gt;\u2009A; p.T458N, and c.1585G\u2009&gt;\u2009A; p.E529K, c.953C\u2009&gt;\u2009T; p.S318L) and a putative truncating variant (c.1413_1414del; p.Y471*) in the\n                      <jats:italic>SRPK3<\/jats:italic>\n                      gene in 9 XLID patients from 5 unrelated families. To validate\n                      <jats:italic>SRPK3<\/jats:italic>\n                      as a novel XLID gene, we established a knockout (KO) model of the\n                      <jats:italic>SRPK3<\/jats:italic>\n                      orthologue in zebrafish.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Together, these data indicate a pathological role of\n                      <jats:italic>SRPK3<\/jats:italic>\n                      in neurodevelopmental disorders. In post\u2010fertilization day 5 larvae (free swimming stage), KO zebrafish exhibited severe deficits in eye movement and swim bladder inflation, mimicking uncontrolled ocular movement and physical clumsiness observed in human patients. In adult KO zebrafish, cerebellar agenesis and behavioral abnormalities were observed, recapitulating human phenotypes of cerebellar atrophy and intellectual disability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      Overall, these results suggest a crucial role of\n                      <jats:italic>SRPK3<\/jats:italic>\n                      in the pathogenesis of syndromic X\u2010linked intellectual disability and provide new insights into brain development, cognitive and ocular dysfunction in both humans and zebrafish. ANN NEUROL 2024;96:914\u2013931\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.27037","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T03:26:11Z","timestamp":1722223571000},"page":"914-931","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>\n                      <i>SRPK3<\/i>\n                    <\/scp>\n                    Is Essential for Cognitive and Ocular Development in Humans and Zebrafish, Explaining X\u2010Linked Intellectual Disability"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1497-4909","authenticated-orcid":false,"given":"Arkaprava","family":"Roychaudhury","sequence":"first","affiliation":[{"name":"Department of Biology Chungnam National University  Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Ri","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biology Chungnam National University  Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae\u2010Ik","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biology Chungnam National University  Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervyn G.","family":"Thomas","sequence":"additional","affiliation":[{"name":"The University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behavior University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahir N.","family":"Khan","sequence":"additional","affiliation":[{"name":"Stanley Manne Children's Research Institute, Ann &amp; Robert H. 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