{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:57:54Z","timestamp":1778806674202,"version":"3.51.4"},"reference-count":26,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T00:00:00Z","timestamp":1664323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The calcium\/calmodulin\u2010dependent serine protein kinase gene (<jats:italic>CASK<\/jats:italic>) is an essential gene in mammals, critical for neurodevelopment. The purpose of this study is to expand the understanding of the diagnosis of <jats:italic>CASK<\/jats:italic>\u2010linked disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials\/Methods<\/jats:title><jats:p>From clinical and genetic mutational analyses, relevant data in 2 Han Chinese patients were collected and analyzed. Real\u2010time quantitative PCR (RT\u2010qPCR) was performed to investigate the <jats:italic>CASK<\/jats:italic> expression levels in the patients. The X\u2010chromosome inactivation (XCI) patterns of the patients and their nuclear families were tested by quantitation of methylation of the polymorphic human androgen receptor (HUMARA) locus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two Han Chinese patients both presented with intellectual disability (ID), microcephaly with pontine and cerebellar hypoplasia (MICPCH). Two de novo mutations of c.82C&gt;T (p.Arg28*) and c.846C&gt;G (p.Tyr282*) in <jats:italic>CASK<\/jats:italic> have been investigated and predicted to be deleterious, which have produced truncated proteins. The functional protein association network of STRING (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/string-db.org\">http:\/\/string\u2010db.org<\/jats:ext-link>) generated three\u2010dimensional (3D) atomic models based on protein sequences in <jats:italic>CASK<\/jats:italic> and two Arg28 and Tyr282 residues were marked. RT\u2010qPCR showed lower copy numbers of <jats:italic>CASK<\/jats:italic> expression in the patients than in their parents, as well as the sex\u2010 and age\u2010 matched control groups. Patient 1 showed a skewed XCI pattern, while no related changes noted in patient 2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Patients carrying different nonsense variants may have different degrees of different clinical phenotypes. This study expands the spectrum of genotype and phenotype correlations of <jats:italic>CASK<\/jats:italic>\u2010linked disorders in the Han Chinese ethnicity and provides new insights into the molecular mechanism.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2065","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T08:10:57Z","timestamp":1664352657000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Two heterozygous mutations in the calcium\/<scp>calmodulin\u2010dependent<\/scp> serine protein kinase gene (<i>CASK<\/i>) in cases with developmental disorders"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9700-526X","authenticated-orcid":false,"given":"Kunfang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurology, Shanghai Children's Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Longlong","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Children's Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Children's Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoguang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Shanghai United Family Hospital  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Children's Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoping","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Children's Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yilin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Children's Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Children's Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaoyan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Shanghai United Family Hospital  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yucai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Children's Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-020-00994-0"},{"key":"e_1_2_11_3_1","first-page":"1229","article-title":"Methylation of Hpall and Hhal sites near the polymorphic CAG repeat in the human androgen\u2010receptor gene correlates with X chromosome inactivation","volume":"51","author":"Cutler Allen R.","year":"1992","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2016.12.005"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-08-02488.1996"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0181791"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.03.015"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540400008952"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22407"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-018-1874-3"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088276"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2020.106323"},{"key":"e_1_2_11_13_1","volume-title":"GeneReviews\u00ae [internet]. 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