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Mutations in the X-linked methyl-CpG-binding protein 2 <jats:italic>(MECP2)<\/jats:italic> gene have been found in up to 95% of classical RTT cases and a lesser proportion of atypical cases. Recently, mutations in another X-linked gene, <jats:italic>CDKL5<\/jats:italic> (cyclin-dependent kinase-like 5) have been found to cause atypical RTT, in particular the early onset seizure (Hanefeld variant) and one female with autism. In this study we screened several cohorts of children for <jats:italic>CDKL5<\/jats:italic> mutations, totaling 316 patients, including individuals with a clinical diagnosis of RTT but who were negative for <jats:italic>MECP2<\/jats:italic> mutations (<jats:italic>n<\/jats:italic> = 102), males with X-linked mental retardation (<jats:italic>n<\/jats:italic> = 9), patients with West syndrome (<jats:italic>n<\/jats:italic> = 52), patients with autism (<jats:italic>n<\/jats:italic> = 59), patients with epileptic encephalopathy (<jats:italic>n<\/jats:italic> = 33), patients with Aicardi syndrome (<jats:italic>n<\/jats:italic> = 7) and other patients with intellectual disability with or without seizures (<jats:italic>n<\/jats:italic> = 54). In all, seven polymorphic variations and four <jats:italic>de novo<\/jats:italic> mutations (c.586C&gt;T [p.S196L]; c.58G&gt;C [p.G20R]; c.2504delC [p.P835fs]; deletion of exons 1 - 3) were identified, and in all instances of the latter the clinical phenotype was that of an epileptic encephalopathy. These results suggest that pathogenic <jats:italic>CDKL5<\/jats:italic> mutations are unlikely to be identified in the absence of severe early-onset seizures and highlight the importance of screening for large intragenic and whole gene deletions.<\/jats:p>","DOI":"10.1375\/twin.13.2.168","type":"journal-article","created":{"date-parts":[[2010,4,16]],"date-time":"2010-04-16T18:19:44Z","timestamp":1271441984000},"page":"168-178","source":"Crossref","is-referenced-by-count":31,"title":["Cyclin-Dependent Kinase-Like 5 (<i>CDKL5<\/i>) Mutation Screening in Rett Syndrome and Related Disorders"],"prefix":"10.1017","volume":"13","author":[{"given":"Rose","family":"White","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gladys","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swetlana","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid E.","family":"Scheffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone C.","family":"Yendle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Bienvenu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Nectoux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn J.","family":"Ellaway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Darmanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XingZhang","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desiree","family":"Cloosterman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Bennetts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veena","family":"Kalra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tod","family":"Fullston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozef","family":"Gecz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy C.","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Christodoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2012,2,21]]},"reference":[{"key":"p_1_135","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"p_2_136","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.041467"},{"key":"p_3_137","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31133"},{"key":"p_4_138","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.033464"},{"key":"p_5_139","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.05.015"},{"key":"p_6_140","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20065"},{"key":"p_7_141","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01520.x"},{"key":"p_8_142","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn197"},{"key":"p_9_143","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201429"},{"key":"p_10_144","first-page":"191","volume":"44","author":"Bourdon V.","year":"2001","journal-title":"Annals of Genetics"},{"key":"p_11_145","doi-asserted-by":"publisher","DOI":"10.1007\/s004390000422"},{"key":"p_12_146","doi-asserted-by":"publisher","DOI":"10.1086\/316913"},{"key":"p_13_147","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.7.1119"},{"key":"p_14_148","unstructured":"Cordova-Fletes, C., Rademacher, N., Muller, I., Mundo-Ayala, J., Morales-Jeanhs, E., Garcia-Ortiz, J., Leon-Gil, A., Rivera, H., Dominguez, M. & Kalscheuer, V. 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