{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:53:56Z","timestamp":1787496836810,"version":"build-2736575974"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"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":["Clinical Genetics"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>CASK<\/jats:italic>\n                    (MIM#300172), encoding a calcium\/calmodulin\u2010dependent serine protein kinase, is crucial for synaptic transmission and gene regulation during neural development. Pathogenic variants of\n                    <jats:italic>CASK<\/jats:italic>\n                    are known to cause several neurodevelopmental disorders, including X\u2010linked intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH). This study introduces a novel, de novo synonymous\n                    <jats:italic>CASK<\/jats:italic>\n                    variant (NM_001367721.1: c.1737G&gt;A, p.(Glu579=)), discovered in a male patient diagnosed with MICPCH, characterized by microcephaly, developmental delay, visual impairment, and myoclonic seizures. The variant disrupts a donor splice\u2010site at the end of exon 18. Transcriptomic analysis of blood identified 12 different\n                    <jats:italic>CASK<\/jats:italic>\n                    transcripts secondary to the synonymous variant. Nearly one third of these transcripts were predicted to result in nonsense mediated decay or protein degradation. Protein modeling revealed structural alterations in the PDZ functional domain of CASK, due to exon 18 deletion. Our findings highlight the utility of transcriptomic analysis in demonstrating the underlying disease mechanism in neurodevelopmental disorders.\n                  <\/jats:p>","DOI":"10.1111\/cge.14610","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T04:45:25Z","timestamp":1724993125000},"page":"764-768","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dissecting\n                    <scp>\n                      <i>CASK<\/i>\n                    <\/scp>\n                    : Novel splice site variant associated with male\n                    <scp>MICPCH<\/scp>\n                    phenotype"],"prefix":"10.1111","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9114-9481","authenticated-orcid":false,"given":"Karina C.","family":"Silveira","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Ambrose","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taryn","family":"Athey","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"},{"name":"Alberta Health Services  Edmonton Zone Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherryl","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8396-6764","authenticated-orcid":false,"given":"Saadet","family":"Mercimek\u2010Andrews","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"},{"name":"Alberta Health Services  Edmonton Zone Alberta Canada"},{"name":"Women and Children's Health Research Institute, University of Alberta  Edmonton Alberta Canada"},{"name":"Neuroscience and Mental Health Institute, University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kannu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"},{"name":"Alberta Health Services  Edmonton Zone Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986706777585040"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14081656"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.194"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398\u2010020\u201000994\u20100"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20107\u201018"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38069"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2021.02.006"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.220"},{"key":"e_1_2_9_10_1","volume-title":"CASK disorders","author":"Moog 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