{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:57:32Z","timestamp":1778806652596,"version":"3.51.4"},"reference-count":23,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T00:00:00Z","timestamp":1485820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec><jats:label\/><jats:p>Mutations in <jats:italic>CASK<\/jats:italic> cause X\u2010linked intellectual disability, microcephaly with pontine and cerebellar hypoplasia, optic atrophy, nystagmus, feeding difficulties, GI hypomotility, and seizures. Here we present a patient with a de novo carboxyl\u2010terminus splice site mutation in <jats:italic>CASK<\/jats:italic> (c.2521\u20102A&gt;G) and clinical features of the rare FG syndrome\u20104 (FGS4). We provide further characterization of genotype\u2013phenotype correlations in <jats:italic>CASK<\/jats:italic> mutations and the presentation of nystagmus and the FGS4 phenotype. There is considerable variability in clinical phenotype among patients with a <jats:italic>CASK<\/jats:italic> mutation, even among variants predicted to have similar functionality. Our patient presented with developmental delay, nystagmus, and severe gastrointestinal and gastroesophageal complications. From a cognitive and neuropsychological perspective, language skills and IQ are within normal range, although visual\u2010motor, motor development, behavior, and working memory were impaired. The c.2521\u20102A&gt;G splice mutation leads to skipping of exon 26 and a 9 base\u2010pair deletion associated with a cryptic splice site, leading to a 28\u2010AA and a 3\u2010AA in\u2010frame deletion, respectively (p.Ala841_Lys843del and p.Ala841_Glu868del). The predominant mutant transcripts contain an aberrant guanylate kinase domain and thus are predicted to degrade CASK's ability to interact with important neuronal and ocular development proteins, including FRMD7. Upregulation of <jats:italic>CASK<\/jats:italic> as well as dysregulation among a number of interactors is also evident by RNA\u2010seq. This is the second <jats:italic>CASK<\/jats:italic> mutation known to us as cause of FGS4. \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38069","type":"journal-article","created":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T08:14:31Z","timestamp":1485850471000},"page":"611-617","source":"Crossref","is-referenced-by-count":15,"title":["A de novo splice site mutation in <i>CASK<\/i> causes FG syndrome\u20104 and congenital nystagmus"],"prefix":"10.1002","volume":"173","author":[{"given":"P.","family":"Dunn","sequence":"first","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. P.","family":"Prigatano","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuropsychology, Barrow Neurological Institute Dignity Health St Joseph's Hospital and Medical Center Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Szelinger","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Roth","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. L.","family":"Siniard","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. M.","family":"Claasen","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. F.","family":"Richholt","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"De Both","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. J.","family":"Corneveaux","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. M.","family":"Moskowitz","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Balak","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I. S.","family":"Piras","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Russell","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. L.","family":"Courtright","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Belnap","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Rangasamy","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Ramsey","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. M.","family":"Opitz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics\/Medical Genetics, School of Medicine University of Utah Salt Lake City Utah"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. W.","family":"Craig","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. J.","family":"Huentelman","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Schrauwen","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix Arizona"},{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,1,31]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.133744.111"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp500"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-18"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp427"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2044-8295.2011.02018.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/1467-8624.00117"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990827)85:5<470::AID-AJMG7>3.0.CO;2-S"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.220"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/35005118"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-015-0256-3"},{"key":"e_1_2_6_17_1","first-page":"1","article-title":"CASK \u00ad related disorders","author":"Moog U","year":"2015","journal-title":"GeneReviews"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00439020"},{"key":"e_1_2_6_19_1","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s00439-002-0863-7","article-title":"Genetic heterogeneity of FG syndrome: A fourth locus (FGS4) maps to Xp11.4\u2010p11.3 in an Italian family","volume":"112","author":"Piluso G","year":"2003","journal-title":"Hum Genet"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.12.018"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/87565640701539469"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003350010170"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1893"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt060"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.38069","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38069","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T06:24:20Z","timestamp":1695536660000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.38069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,31]]},"references-count":23,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,3]]}},"alternative-id":["10.1002\/ajmg.a.38069"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.38069","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,31]]}}}