{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T05:45:13Z","timestamp":1775195113821,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,5,2]],"date-time":"2016-05-02T00:00:00Z","timestamp":1462147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Legacy Heritage Bio-Medical program of the Israel Science Foundation","award":["1395\/12"],"award-info":[{"award-number":["1395\/12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:p>Recessive <jats:italic><jats:styled-content style=\"fixed-case\">CRB2<\/jats:styled-content><\/jats:italic> mutations were recently reported to cause both steroid resistant nephrotic syndrome and prenatal onset ventriculomegaly with kidney disease. We report two Ashkenazi Jewish siblings clinically diagnosed with ciliopathy. Both presented with severe congenital hydrocephalus and mild urinary tract anomalies. One affected sibling also has lung hypoplasia and heart defects. Exome sequencing and further <jats:italic><jats:styled-content style=\"fixed-case\">CRB2<\/jats:styled-content><\/jats:italic> analysis revealed that both siblings are compound heterozygotes for <jats:italic><jats:styled-content style=\"fixed-case\">CRB2<\/jats:styled-content><\/jats:italic> mutations p.<jats:styled-content style=\"fixed-case\">N800K<\/jats:styled-content> and p.<jats:styled-content style=\"fixed-case\">Gly1036Alafs<\/jats:styled-content>*43, and heterozygous for a deleterious splice variant in the ciliopathy gene <jats:italic><jats:styled-content style=\"fixed-case\">TTCB21<\/jats:styled-content><\/jats:italic>. <jats:italic><jats:styled-content style=\"fixed-case\">CRB2<\/jats:styled-content><\/jats:italic> is a polarity protein which plays a role in ciliogenesis and ciliary function. Biallelic <jats:italic><jats:styled-content style=\"fixed-case\">CRB2<\/jats:styled-content><\/jats:italic> mutations in animal models result in phenotypes consistent with ciliopathy. This report expands the phenotype of <jats:italic><jats:styled-content style=\"fixed-case\">CRB2<\/jats:styled-content><\/jats:italic> mutations to include lung hypoplasia and uretero\u2010pelvic renal anomalies, and confirms cardiac malformation as a feature. We suggest that <jats:italic><jats:styled-content style=\"fixed-case\">CRB2<\/jats:styled-content><\/jats:italic>\u2010associated disease is a new ciliopathy syndrome with possible digenic\/triallelic inheritance, as observed in other ciliopathies. Clinically, <jats:italic><jats:styled-content style=\"fixed-case\">CRB2<\/jats:styled-content><\/jats:italic> should be assessed when ciliopathy is suspected, especially in Ashkenazi Jews, where we found that p.<jats:styled-content style=\"fixed-case\">N800K<\/jats:styled-content> carrier frequency is 1 of 64. Patients harboring <jats:italic><jats:styled-content style=\"fixed-case\">CRB2<\/jats:styled-content><\/jats:italic> mutations should be tested for the complete range of ciliopathy manifestations.<\/jats:p>","DOI":"10.1111\/cge.12764","type":"journal-article","created":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T07:03:29Z","timestamp":1456815809000},"page":"540-544","source":"Crossref","is-referenced-by-count":21,"title":["Expanding the phenotype of <scp>CRB2<\/scp> mutations\u00a0\u2013\u00a0A new ciliopathy syndrome?"],"prefix":"10.1111","volume":"90","author":[{"given":"R.","family":"Jaron","sequence":"first","affiliation":[{"name":"Medical Genetics Institute Shaare Zedek Medical Center  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Rosenfeld","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute Shaare Zedek Medical Center  Jerusalem Israel"},{"name":"Faculty of Medicine The Hebrew University of Jerusalem Medical School  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Zahdeh","sequence":"additional","affiliation":[{"name":"Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science Jerusalem, Edmond J. 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