{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T03:02:14Z","timestamp":1761102134428},"reference-count":13,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,9,29]],"date-time":"2014-09-29T00:00:00Z","timestamp":1411948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"European Union Seventh Framework Programme FP7\/2007-2013","award":["602531"],"award-info":[{"award-number":["602531"]}]},{"name":"Italian Minister of Health","award":["RF-2009-1525669"],"award-info":[{"award-number":["RF-2009-1525669"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,11]]},"abstract":"Summary<\/jats:title>Objective<\/jats:title>Mutations involving the cyclin\u2010dependent kinase\u2010like 5<\/jats:italic> (CDKL<\/jats:styled-content>5<\/jats:italic>) gene cause an early onset epileptic encephalopathy (EE<\/jats:styled-content>) with severe neurologic impairment and a skewed 12:1 female\u2010to\u2010male ratio. To date, 18 mutations have been described in boys. We analyzed our cohort of boys with early onset EE<\/jats:styled-content> to assess the diagnostic yield of our molecular approach.<\/jats:p><\/jats:sec>Methods<\/jats:title>We studied 74 boys who presented early onset severe seizures, including infantile spasms and developmental delay, in the setting of EE<\/jats:styled-content>, using Sanger sequencing, next\u2010generation sequencing (NGS<\/jats:styled-content>) and multiplex ligation\u2010dependent probe amplification (MLPA<\/jats:styled-content>).<\/jats:p><\/jats:sec>Results<\/jats:title>We identified alterations involving CDKL<\/jats:styled-content>5<\/jats:italic> in four boys (5.4%) using NGS<\/jats:styled-content> in one and MLPA<\/jats:styled-content> in three. Three of four mutations were indicative of somatic mosaicism.<\/jats:p><\/jats:sec>Significance<\/jats:title>CDKL<\/jats:styled-content>5<\/jats:italic> gene mutations accounted for 5.4% of boys with early onset EE<\/jats:styled-content>. Somatic mosaic mutations might be even more represented than germline mutations, probably because their less deleterious effect enhances viability of the male embryo. The molecular approach used for CDKL<\/jats:styled-content>5<\/jats:italic> screening remarkably influences the diagnostic yield in boys. Diagnosis is optimized by Sanger sequencing combined with array\u2010based methods or MLPA<\/jats:styled-content>; alternatively, NGS<\/jats:styled-content> targeted resequencing designed to also detect copy number alterations, may be performed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12803","type":"journal-article","created":{"date-parts":[[2014,9,29]],"date-time":"2014-09-29T22:15:27Z","timestamp":1412028927000},"page":"1748-1753","source":"Crossref","is-referenced-by-count":23,"title":["Optimizing the molecular diagnosis of CDKL<\/scp>5<\/i> gene\u2013related epileptic encephalopathy in boys"],"prefix":"10.1111","volume":"55","author":[{"given":"Davide","family":"Mei","sequence":"first","affiliation":[{"name":"Pediatric Neurology and Neurogenetics Unit and Laboratories A. Meyer Children's Hospital\u2014University of Florence Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Darra","sequence":"additional","affiliation":[{"name":"Department of Life and Reproduction Sciences\u2014Section of Child Neurology and Psychiatry University of Verona Verona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Barba","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Neurogenetics Unit and Laboratories A. Meyer Children's Hospital\u2014University of Florence Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Marini","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Neurogenetics Unit and Laboratories A. Meyer Children's Hospital\u2014University of Florence Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Fontana","sequence":"additional","affiliation":[{"name":"Department of Life and Reproduction Sciences\u2014Section of Child Neurology and Psychiatry University of Verona Verona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Chiti","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Neurogenetics Unit and Laboratories A. Meyer Children's Hospital\u2014University of Florence Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Parrini","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Neurogenetics Unit and Laboratories A. Meyer Children's Hospital\u2014University of Florence Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernardo","family":"Dalla Bernardina","sequence":"additional","affiliation":[{"name":"Department of Life and Reproduction Sciences\u2014Section of Child Neurology and Psychiatry University of Verona Verona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renzo","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Neurogenetics Unit and Laboratories A. Meyer Children's Hospital\u2014University of Florence Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,9,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1159\/000331333","article-title":"CDKL5\u2010related disorders: from clinical description to molecular genetics","volume":"2","author":"Bahi\u2010Buisson N","year":"2012","journal-title":"Mol Syndromol"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2010.03889.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03656.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2012.12.030"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02308.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.049452"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03174.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2009.01194.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33037"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31820605f5"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.028"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12203"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-S11-S1"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.12803","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.12803","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T16:07:29Z","timestamp":1696349249000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.12803"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,29]]},"references-count":13,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2014,11]]}},"alternative-id":["10.1111\/epi.12803"],"URL":"https:\/\/doi.org\/10.1111\/epi.12803","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,29]]}}}