{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:56:37Z","timestamp":1792180597821,"version":"4.4.0"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,8,19]],"date-time":"2013-08-19T00:00:00Z","timestamp":1376870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"name":"German Federal Ministry of Education and Research","award":["01GM1211A"],"award-info":[{"award-number":["01GM1211A"]}]},{"name":"Hacettepe University Research Foundation"},{"name":"European Research Area Network \u201cE-RARE\u201d","award":["2.01.101.010"],"award-info":[{"award-number":["2.01.101.010"]}]},{"name":"European Research Area Network \u201cE-RARE\u201d","award":["108S420"],"award-info":[{"award-number":["108S420"]}]},{"name":"European Research Area Network \u201cE-RARE\u201d","award":["R07197KS"],"award-info":[{"award-number":["R07197KS"]}]},{"name":"EMBO long-term fellowship"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    We have characterized a novel autosomal recessive Crouzon\u2010like craniosynostosis syndrome in a 12\u2010affected member family from Antakya, Turkey, the presenting features of which include: multiple suture synostosis, midface hypoplasia, variable degree of exophthalmos, relative prognathism, a beaked nose, and conductive hearing loss. Homozygosity mapping followed by targeted next\u2010generation sequencing identified a c.479+6T&gt;G mutation in the interleukin 11 receptor alpha gene (\n                    <jats:italic>IL11RA<\/jats:italic>\n                    ) on chromosome 9p21. This donor splice\u2010site mutation leads to a high percentage of aberrant\n                    <jats:italic>IL11RA<\/jats:italic>\n                    <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                    transcripts in an affected individual and altered\n                    <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                    splicing determined by in vitro exon trapping. An extended\n                    <jats:italic>IL11RA<\/jats:italic>\n                    mutation screen was performed in a cohort of 79 patients with an initial clinical diagnosis of Crouzon syndrome, pansynostosis, or unclassified syndromic craniosynostosis. We identified mutations segregating with the disease in five families: a German patient of Turkish origin and a Turkish family with three affected sibs all of whom were homozygous for the previously identified\n                    <jats:italic>IL11RA<\/jats:italic>\n                    c.479+6T&gt;G mutation; a family with pansynostosis with compound heterozygous missense mutations, p.Pro200Thr and p.Arg237Pro; and two further Turkish families with Crouzon\u2010like syndrome carrying the homozygous nonsense mutations p.Tyr232* and p.Arg292*. Using transient coexpression in HEK293T and COS7 cells, we demonstrated dramatically reduced IL11\u2010mediated STAT3 phosphorylation for all mutations. Immunofluorescence analysis of mouse Il11ra demonstrated specific protein expression in cranial mesenchyme which was localized around the coronal suture tips and in the lambdoidal suture. In situ hybridization analysis of adult zebrafish also detected\n                    <jats:italic>zfil11ra<\/jats:italic>\n                    expression in the coronal suture between the overlapping frontal and parietal plates. This study demonstrates that mutations in the\n                    <jats:italic>IL11RA<\/jats:italic>\n                    gene cause an autosomal recessive Crouzon\u2010like craniosynostosis.\n                  <\/jats:p>","DOI":"10.1002\/mgg3.28","type":"journal-article","created":{"date-parts":[[2013,8,19]],"date-time":"2013-08-19T02:24:41Z","timestamp":1376879081000},"page":"223-237","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Mutations in the interleukin receptor\n                    <i>\n                      <scp>IL<\/scp>\n                      11\n                      <scp>RA<\/scp>\n                    <\/i>\n                    cause autosomal recessive Crouzon\u2010like craniosynostosis"],"prefix":"10.1002","volume":"1","author":[{"given":"Katharina","family":"Keupp","sequence":"first","affiliation":[{"name":"Center for Molecular Medicine Cologne (CMMC) University of Cologne 50931 Cologne Germany"},{"name":"Institute of Human Genetics University of Cologne 50931 Cologne Germany"},{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging\u2010Associated Diseases (CECAD) University of Cologne 50931 Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne (CMMC) University of Cologne 50931 Cologne Germany"},{"name":"Institute of Human Genetics University of Cologne 50931 Cologne Germany"},{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging\u2010Associated Diseases (CECAD) University of Cologne 50931 Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Vargel","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Hacettepe University Medical Faculty 06100 Ankara Turkey"},{"name":"Department of Plastic and Reconstructive Surgery Medical Faculty Kirikkale University 71100 Kirikkale Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Hoischen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Nijmegen Medical Centre 6500HB Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology University of Bristol BS8 1TD Bristol U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kornelia","family":"Neveling","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Nijmegen Medical Centre 6500HB Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasemin","family":"Alanay","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Pediatric Genetics Unit Hacettepe University Medical Faculty 06100 Ankara Turkey"},{"name":"Department of Pediatrics Pediatric Genetics Unit Acibadem University 34457 \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Uz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Gene Mapping Laboratory, Hacettepe University Medical Faculty 06100 Ankara Turkey"},{"name":"Department of Biology Duzce University 81620 Duzce Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nursel","family":"Elcio\u011flu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics Marmara University Medical Faculty 34668 Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Rachwalski","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne (CMMC) University of Cologne 50931 Cologne Germany"},{"name":"Institute of Human Genetics University of Cologne 50931 Cologne 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