{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T22:08:10Z","timestamp":1790546890920,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,10,24]],"date-time":"2017-10-24T00:00:00Z","timestamp":1508803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:p>Otofaciocervical syndrome (<jats:styled-content style=\"fixed-case\">OFCS<\/jats:styled-content>) is a rare disorder characterized by facial anomalies, cup\u2010shaped low\u2010set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies, and mild intellectual disability. Autosomal dominant cases are caused by deletions or point mutations of <jats:italic><jats:styled-content style=\"fixed-case\">EYA1<\/jats:styled-content><\/jats:italic>. A single family with an autosomal recessive form of <jats:styled-content style=\"fixed-case\">OFCS<\/jats:styled-content> and a homozygous missense mutation in <jats:italic><jats:styled-content style=\"fixed-case\">PAX1<\/jats:styled-content><\/jats:italic> gene has been described.<\/jats:p><jats:p>We report whole exome sequencing of 4 members of a consanguineous family in which 2 children, showing features of <jats:styled-content style=\"fixed-case\">OFCS<\/jats:styled-content>, expired from severe combined immunodeficiency (<jats:styled-content style=\"fixed-case\">SCID<\/jats:styled-content>). To date, the co\u2010occurrence of <jats:styled-content style=\"fixed-case\">OFCS<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">SCID<\/jats:styled-content> has never been reported. We found a nonsense homozygous mutation in <jats:italic><jats:styled-content style=\"fixed-case\">PAX1<\/jats:styled-content><\/jats:italic> gene in the 2 affected children. In mice, Pax1 is required for the formation of specific skeletal structures as well as for the development of a fully functional thymus. The mouse model strongly supports the hypothesis that <jats:styled-content style=\"fixed-case\">PAX1<\/jats:styled-content> depletion in our patients caused thymus aplasia responsible for <jats:styled-content style=\"fixed-case\">SCID<\/jats:styled-content>.<\/jats:p><jats:p>This report provides evidence that bi\u2010allelic null <jats:italic><jats:styled-content style=\"fixed-case\">PAX1<\/jats:styled-content><\/jats:italic> mutations may lead to a multi\u2010system autosomal recessive disorders, where <jats:styled-content style=\"fixed-case\">SCID<\/jats:styled-content> might represent the main feature.<\/jats:p>","DOI":"10.1111\/cge.13085","type":"journal-article","created":{"date-parts":[[2017,6,28]],"date-time":"2017-06-28T10:44:37Z","timestamp":1498646677000},"page":"664-668","source":"Crossref","is-referenced-by-count":56,"title":["A novel <i><scp>PAX1<\/scp><\/i> null homozygous mutation in autosomal recessive otofaciocervical syndrome associated with severe combined immunodeficiency"],"prefix":"10.1111","volume":"92","author":[{"given":"I.","family":"Paganini","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio,\u201d Medical Genetics Unit University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Sestini","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio,\u201d Medical Genetics Unit University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.L.","family":"Capone","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio,\u201d Medical Genetics Unit University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.L.","family":"Putignano","sequence":"additional","affiliation":[{"name":"Department 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