{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:42:41Z","timestamp":1788316961708,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,2,8]],"date-time":"2020-02-08T00:00:00Z","timestamp":1581120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1103741"],"award-info":[{"award-number":["1103741"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pathogenic variants in the cyclin\u2010dependent kinase\u2010like 5 (<jats:italic>CDKL5<\/jats:italic>) gene cause the neurodevelopmental disorder, the CDKL5 deficiency disorder. Reports of individuals with pathogenic variants in <jats:italic>CDKL5<\/jats:italic> without seizures are exceedingly rare, and in\u2010depth analyses of their variants have been lacking. Whole\u2010genome sequencing was performed on a 29\u2010year\u2010old female with mild intellectual disability who, in the absence of overt seizures, presented with multiple episodes of altered mental status over a 24\u2010year period. Clinical history was supplemented by a parent completed questionnaire from the International CDKL5 Disorder Database. We identified a de novo heterozygous variant in <jats:italic>CDKL5<\/jats:italic> (NM_003159.2:c.645T&gt;A;p.Ser215Arg). In\u2010depth computational analysis performed to predict the impact of the variant on protein structure and function demonstrated that the variant was likely pathogenic. In this light, cell\u2010based studies showed that the S215R substitution causes a marked reduction in CDKL5 kinase activity. Similarities between our case and one previously reported case are striking. These cases, both without seizures but with apparent behavioral symptomatology, together question whether seizures are mandatory in this neurodevelopmental disorder.<\/jats:p>","DOI":"10.1002\/ajmg.a.61504","type":"journal-article","created":{"date-parts":[[2020,2,8]],"date-time":"2020-02-08T10:13:21Z","timestamp":1581156801000},"page":"1217-1222","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Expanding the phenotype of the CDKL5 deficiency disorder: Are seizures mandatory?"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1301-7317","authenticated-orcid":false,"given":"Conor I.","family":"MacKay","sequence":"first","affiliation":[{"name":"Telethon Kids Institute The University of Western Australia  Perth Western Australia 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