Mutations in the interleukin receptor IL11RA cause autosomal recessive crouzon-like craniosynostosis

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dc.contributor.authorKeupp, Katharina
dc.contributor.authorLi, Yun
dc.contributor.authorVargel, İbrahim
dc.contributor.authorHoischen, Alexander
dc.contributor.authorRichardson, Rebecca
dc.contributor.authorNeveling, Kornelia
dc.contributor.authorWollnik, Bernd
dc.date.accessioned2020-04-30T13:32:50Z
dc.date.available2020-04-30T13:32:50Z
dc.date.issued2013
dc.departmentDÜ, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümüen_US
dc.description.abstractWe have characterized a novel autosomal recessive Crouzon-like craniosynostosis syndrome in a 12-affected 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-generation sequencing identified a c.479+6T>G mutation in the interleukin 11 receptor alpha gene (IL11RA) on chromosome 9p21. This donor splice-site mutation leads to a high percentage of aberrant IL11RA mRNA transcripts in an affected individual and altered mRNA splicing determined by in vitro exon trapping. An extended IL11RA 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 IL11RA c.479+6T>G mutation; a family with pansynostosis with compound heterozygous missense mutations, p.Pro200Thr and p.Arg237Pro; and two further Turkish families with Crouzon-like syndrome carrying the homozygous nonsense mutations p.Tyr232* and p.Arg292*. Using transient coexpression in HEK293T and COS7 cells, we demonstrated dramatically reduced IL11-mediated 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 zfil11ra expression in the coronal suture between the overlapping frontal and parietal plates. This study demonstrates that mutations in the IL11RA gene cause an autosomal recessive Crouzon-like craniosynostosis. © 2013 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.en_US
dc.identifier.doi10.1002/mgg3.28en_US
dc.identifier.endpage237en_US
dc.identifier.issn2324-9269
dc.identifier.issue4en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage223en_US
dc.identifier.urihttps://dx.doi.org/10.1002/mgg3.28
dc.identifier.urihttps://hdl.handle.net/20.500.12684/453
dc.identifier.volume1en_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherWiley-Blackwellen_US
dc.relation.ispartofMolecular Genetics and Genomic Medicineen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAutosomal recessive craniosynostosis; Crouzon; FGFR2; IL11RA; Supernumerary teeth; Tooth erruptionen_US
dc.titleMutations in the interleukin receptor IL11RA cause autosomal recessive crouzon-like craniosynostosisen_US
dc.typeArticleen_US

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