{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T01:27:55Z","timestamp":1773365275563,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,3,10]],"date-time":"2015-03-10T00:00:00Z","timestamp":1425945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Nijmegen Institute for Molecular Life Sciences"},{"name":"The Netherlands Organization for Scientific Research"},{"name":"ERC Consolidator Grant","award":["#310372"],"award-info":[{"award-number":["#310372"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim of this study was to determine the genetic and immunological defects underlying familial manifestations of an autoimmune disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome sequencing was performed on the index patient with various manifestations of autoimmunity, including hypothyroidism, vitiligo and alopecia. Peripheral blood mononuclear cells and <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> of family members were used for functional and genetic testing of the candidate variants obtained by <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>anger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Exome sequencing identified 233 rare, coding and nonsynonymous variants in the index patient; five were highly conserved and affect genes that have a possible role in autoimmunity. Only a heterozygous missense mutation in the suppressor of cytokine signalling 4 gene (<jats:italic><jats:styled-content style=\"fixed-case\">SOCS<\/jats:styled-content>4<\/jats:italic>) cosegregated with the autoimmune disorder in the family. <jats:styled-content style=\"fixed-case\">SOCS<\/jats:styled-content>4 is a known inhibitor of epidermal growth factor (<jats:styled-content style=\"fixed-case\">EGF<\/jats:styled-content>) receptor signalling, and functional studies demonstrated specific upregulation of <jats:styled-content style=\"fixed-case\">EGF<\/jats:styled-content>\u2010dependent immune stimulation in affected family members.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We present a family with an autoimmune disorder, probably resulting from dysregulated immune responses due to mutations in <jats:italic><jats:styled-content style=\"fixed-case\">SOCS<\/jats:styled-content>4<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.12351","type":"journal-article","created":{"date-parts":[[2015,1,31]],"date-time":"2015-01-31T06:38:22Z","timestamp":1422686302000},"page":"203-210","source":"Crossref","is-referenced-by-count":10,"title":["A missense mutation underlies defective <scp>SOCS<\/scp>4 function in a family with autoimmunity"],"prefix":"10.1111","volume":"278","author":[{"given":"P.","family":"Arts","sequence":"first","affiliation":[{"name":"Department of Human Genetics Radboud Institute for Molecular Life Sciences Donders Centre for Neuroscience Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. S.","family":"Plantinga","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. M.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Immunology and Infectious Disease Emma Children's Hospital Academic Medical Center University of Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Gilissen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud Institute for Molecular Life Sciences Donders Centre for Neuroscience Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. A.","family":"Veltman","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud Institute for Molecular Life Sciences Donders Centre for Neuroscience Radboud University Medical Center Nijmegen The Netherlands"},{"name":"Department of Clinical Genetics Maastricht University Medical Centre Maastricht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. S.","family":"van Trotsenburg","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Emma Children's Hospital Academic Medical Center University of Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. L.","family":"van de Veerdonk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. 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