{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T05:50:31Z","timestamp":1777269031367,"version":"3.51.4"},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T00:00:00Z","timestamp":1607472000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001371"],"award-info":[{"award-number":["82001371"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Shanghai Municipal Science and Technology Commission","doi-asserted-by":"crossref","award":["16ZR1421700"],"award-info":[{"award-number":["16ZR1421700"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shanghai Municipal Health Commission","award":["2018YQ24"],"award-info":[{"award-number":["2018YQ24"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Mutations in <jats:italic>CNKSR2<\/jats:italic> have been described in patients with neurodevelopmental disorders characterized by childhood epilepsy, language deficits, and attention problems. The encoded protein plays an important role in synaptic function.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>Whole-exome sequencing was applied to detect pathogenic variants in a patient with clinical symptoms of psychomotor development, attention deficit, poor logical thinking ability, and an introverted personality, but without epilepsy or any significant electroencephalogram changes. Genetic study revealed a splicing mutation (c.1904\u2009+\u20091G\u2009&gt;\u2009A) and RT-PCR revealed aberrant splicing of exon 16, leading to a reading-frame shift and a truncated protein in the PH domain.\n<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This is the first report of a splicing variant of <jats:italic>CNKSR2<\/jats:italic>, and the unique clinical features of this pedigree will help extend our understanding of the genetic and phenotypic spectra of <jats:italic>CNKSR2<\/jats:italic>-related disorders.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12920-020-00844-4","type":"journal-article","created":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T18:18:08Z","timestamp":1607537888000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Psychomotor development and attention problems caused by a splicing variant of CNKSR2"],"prefix":"10.1186","volume":"13","author":[{"given":"Yi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiwen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihua","family":"Ge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4147-5291","authenticated-orcid":false,"given":"Ruen","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,12,9]]},"reference":[{"issue":"1","key":"844_CR1","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s13073-017-0498-x","volume":"9","author":"AB Wilfert","year":"2017","unstructured":"Wilfert AB, Sulovari A, Turner TN, Coe BP, Eichler EE. Recurrent de novo mutations in neurodevelopmental disorders: properties and clinical implications. Genome Med. 2017;9(1):101. https:\/\/doi.org\/10.1186\/s13073-017-0498-x.","journal-title":"Genome Med"},{"issue":"7","key":"844_CR2","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/j.cub.2014.02.036","volume":"24","author":"J Lim","year":"2014","unstructured":"Lim J, Ritt DA, Zhou M, Morrison DK. The CNK2 scaffold interacts with vilse and modulates Rac cycling during spine morphogenesis in hippocampal neurons. Curr Biol. 2014;24(7):786\u201392. https:\/\/doi.org\/10.1016\/j.cub.2014.02.036.","journal-title":"Curr Biol"},{"issue":"5","key":"844_CR3","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1002\/ana.24274","volume":"76","author":"AK Vaags","year":"2014","unstructured":"Vaags AK, Bowdin S, Smith ML, Gilbert-Dussardier B, Brocke-Holmefjord KS, Sinopoli K, et al. Absent CNKSR2 causes seizures and intellectual, attention, and language deficits. Ann Neurol. 2014;76(5):758\u201364. https:\/\/doi.org\/10.1002\/ana.24274.","journal-title":"Ann Neurol"},{"issue":"7","key":"844_CR4","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1002\/ajmg.a.36902","volume":"167","author":"U Aypar","year":"2015","unstructured":"Aypar U, Wirrell EC, Hoppman NL. CNKSR2 deletions: a novel cause of X-linked intellectual disability and seizures. Am J Med Genet A. 2015;167(7):1668\u201370. https:\/\/doi.org\/10.1002\/ajmg.a.36902.","journal-title":"Am J Med Genet A"},{"issue":"3","key":"844_CR5","doi-asserted-by":"publisher","first-page":"e40","DOI":"10.1111\/epi.13666","volume":"58","author":"JA Damiano","year":"2017","unstructured":"Damiano JA, Burgess R, Kivity S, Lerman-Sagie T, Afawi Z, Scheffer IE, et al. Frequency of CNKSR2 mutation in the X-linked epilepsy-aphasia spectrum. Epilepsia. 2017;58(3):e40\u20133. https:\/\/doi.org\/10.1111\/epi.13666.","journal-title":"Epilepsia"},{"issue":"2","key":"844_CR6","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1159\/000335159","volume":"2","author":"G Houge","year":"2012","unstructured":"Houge G, Rasmussen IH, Hovland R. Loss-of-function CNKSR2 mutation is a likely cause of non-syndromic X-linked intellectual disability. Mol Syndromol. 2012;2(2):60\u20133.","journal-title":"Mol Syndromol"},{"issue":"12","key":"844_CR7","doi-asserted-by":"publisher","first-page":"570","DOI":"10.12998\/wjcc.v6.i12.570","volume":"6","author":"Y Sun","year":"2018","unstructured":"Sun Y, Liu YD, Xu ZF, Kong QX, Wang YL. CNKSR2 mutation causes the X-linked epilepsy-aphasia syndrome: A case report and review of literature. World J Clin Cases. 2018;6(12):570\u20136. https:\/\/doi.org\/10.12998\/wjcc.v6.i12.570.","journal-title":"World J Clin Cases"},{"issue":"23","key":"844_CR8","doi-asserted-by":"publisher","first-page":"13259","DOI":"10.1073\/pnas.96.23.13259","volume":"96","author":"M Therrien","year":"1999","unstructured":"Therrien M, Wong AM, Kwan E, Rubin GM. Functional analysis of CNK in RAS signaling. Proc Natl Acad Sci U S A. 1999;96(23):13259\u201363.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"844_CR9","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1006\/bbrc.2000.2475","volume":"270","author":"I Yao","year":"2000","unstructured":"Yao I, Ohtsuka T, Kawabe H, Matsuura Y, Takai Y, Hata Y. Association of membrane-associated guanylate kinase-interacting protein-1 with Raf-1. Biochem Biophys Res Commun. 2000;270(2):538\u201342. https:\/\/doi.org\/10.1006\/bbrc.2000.2475.","journal-title":"Biochem Biophys Res Commun"}],"container-title":["BMC Medical Genomics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-020-00844-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12920-020-00844-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-020-00844-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T18:21:31Z","timestamp":1607538091000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedgenomics.biomedcentral.com\/articles\/10.1186\/s12920-020-00844-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":9,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["844"],"URL":"https:\/\/doi.org\/10.1186\/s12920-020-00844-4","relation":{},"ISSN":["1755-8794"],"issn-type":[{"value":"1755-8794","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12]]},"assertion":[{"value":"26 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was approved by the Committee on Ethics of the Shanghai Children\u2019s Medical Center (SCMCIRB-K2016013) and was performed in accordance with the Declaration of Helsinki. After explanation of the possible consequences of the study, written informed consent was obtained from both of the patient\u2019s father and mother, and from both of the mother\u2019s parents.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}],"article-number":"182"}}