{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:33:05Z","timestamp":1785717185957,"version":"3.56.0"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,8,15]],"date-time":"2019-08-15T00:00:00Z","timestamp":1565827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["241995"],"award-info":[{"award-number":["241995"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Eight different deletions and point variants of the X\u2010chromosomal gene <jats:italic>CNKSR2<\/jats:italic> have been reported in families with males presenting intellectual disability (ID) and epilepsy. Obligate carrier females with a frameshift variant in the N\u2010terminal protein coding part of <jats:italic>CNKSR2<\/jats:italic> or with a deletion of the complete gene are not affected. Only for one C\u2010terminal nonsense variant, two carrier females were mildly affected by seizures without or with mild motor and language delay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Exome sequencing was performed in one female child of a Dutch family, presenting seizures, mild ID, facial dysmorphisms, and abnormalities of the extremities. Potential causative variants were validated by Sanger sequencing. X\u2010chromosome\u2010inactivation (XCI) analysis was performed by methylation\u2010sensitive PCR and fragment\u2010length analysis of the androgen\u2010receptor CAG repeat polymorphism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a de novo variant, c.2304G&gt;A (p.(Trp768*)), in the C\u2010terminal protein coding part of the X\u2010chromosomal gene <jats:italic>CNKSR2<\/jats:italic> in a female patient with seizures and mild ID. Sanger sequencing confirmed the presence of this nonsense variant. XCI analysis showed a mild skewing of X inactivation (20:80) in the blood of our patient. Our variant is the second C\u2010terminal\u2013affecting <jats:italic>CNKSR2<\/jats:italic> variant described in neurologically affected females.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results indicate that <jats:italic>CNKSR2<\/jats:italic> nonsense variants in the C\u2010terminal coding part can result in ID with seizures in female variant carriers.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.861","type":"journal-article","created":{"date-parts":[[2019,8,15]],"date-time":"2019-08-15T09:10:17Z","timestamp":1565860217000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A de novo variant in the X\u2010linked gene <i>CNKSR2<\/i> is associated with seizures and mild intellectual disability in a female patient"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5552-3488","authenticated-orcid":false,"given":"Daniel L.","family":"Polla","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center Nijmegen The Netherlands"},{"name":"CAPES Foundation Ministry of Education of Brazil Bras\u00edlia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet R.","family":"Saunders","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert B. A.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"van Bokhoven","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjan P. M.","family":"de Brouwer","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36902"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2004.02.037"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03479"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.09.002"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2653"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13666"},{"key":"e_1_2_6_8_1","volume-title":"Diagnostic and statistical manual of mental disorders","author":"DSM\u20105","year":"2013"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2540"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2929"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/363309b0"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000335159"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl048"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.193"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2002.01987.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-1096com"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrdd.10031"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.02.036"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2009.06.016"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.02.018"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.310204"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90244-K"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002212"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/dnares\/5.6.355"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2443.2002.00589.x"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.109"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560060128"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v6.i12.570"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24274"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2325"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.17.11889"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmgg3.861","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.861","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.861","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.861","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T10:55:54Z","timestamp":1708512954000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,15]]},"references-count":32,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1002\/mgg3.861"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.861","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,15]]},"assertion":[{"value":"2019-02-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00861"}}