{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T06:05:56Z","timestamp":1759730756420,"version":"3.41.2"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T00:00:00Z","timestamp":1595289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000053","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":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>CASK<\/jats:italic> is an X\u2010linked gene in mammals and its deletion in males is incompatible with life. <jats:italic>CASK<\/jats:italic> heterozygous mutations in female patients associate with intellectual disability, microcephaly, pontocerebellar hypoplasia, and optic nerve hypoplasia, whereas <jats:italic>CASK<\/jats:italic> hemizygous mutations in males manifest as early infantile epileptic encephalopathy with a grim prognosis. Here, we report a rare case of survival of a male patient harboring a <jats:italic>CASK<\/jats:italic> null mutation to adolescent age.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Trio whole exome sequencing analysis was performed from blood genomic DNA. Magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and electroencephalogram (EEG) analyses were performed to determine anomalies in brain development, metabolite concentrations, and electrical activity, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Trio\u2010WES analysis identified a <jats:italic>de novo<\/jats:italic> c.79C&gt;T (p.Arginine27Ter) mutation in <jats:italic>CASK<\/jats:italic> causing a premature translation termination at the very N\u2010terminus of the protein. The 17\u2010years, and 11\u2010month\u2010old male patient displayed profound intellectual disability, microcephaly, dysmorphism, ponto\u2010cerebellar hypoplasia, and intractable epilepsy. His systemic symptoms included overall reduced somatic growth, dysautonomia, ventilator and G tube dependence, and severe osteopenia. Brain MRI revealed a severe cerebellar and brain stem hypoplasia with progressive cerebral atrophy. EEG spectral analysis revealed a global functional defect with generalized background slowing and delta waves dominating even in the awake state.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This case study is the first to report survival of a male patient carrying a <jats:italic>CASK<\/jats:italic> loss\u2010of\u2010function mutation to adolescence and highlights that improved palliative care could extend survival. Moreover, the genomic position encoding Arg27 in <jats:italic>CASK<\/jats:italic> may possess an increased susceptibility to mutations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1426","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T01:05:00Z","timestamp":1595379900000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Survival of a male patient harboring CASK Arg27Ter mutation to adolescence"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6922-9554","authenticated-orcid":false,"given":"Konark","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Fralin Biomedical Research Institute at Virginia Tech Carilion Roanoke VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paras A.","family":"Patel","sequence":"additional","affiliation":[{"name":"Fralin Biomedical Research Institute at Virginia Tech Carilion Roanoke VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepa S.","family":"Rajan","sequence":"additional","affiliation":[{"name":"Children's Hospital of Pittsburgh of UPMC University of Pittsburgh Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie E. 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