Novel TSHR mutations in consanguineous families with congenital nongoitrous hypothyroidism

dc.contributor.authorMorgan, Neil V.
dc.contributor.authorForman, Julia R.
dc.contributor.authorAycan, Zehra
dc.contributor.authorBöber, Ece
dc.contributor.authorCesur, Yaşar
dc.contributor.authorKirby, Gail A.
dc.contributor.authorPasha, Shanaz S.
dc.contributor.authorÇetinkaya, Semra Çağlar
dc.contributor.authorBaş, Veysel Nihat
dc.contributor.authorDemir, Korcan
dc.contributor.authorYuca, Sevil Arı
dc.contributor.authorMeyer, Esther
dc.contributor.authorHögler, Wolfgang
dc.contributor.authorTimothy Barrett, Timothy
dc.contributor.authorMäher, Eamonn Richard
dc.contributor.buuauthorCangül, Hakan
dc.contributor.buuauthorSağlam, Halil
dc.contributor.buuauthorYakut, Tahsin
dc.contributor.buuauthorGülten, Tuna
dc.contributor.buuauthorTarım, Ömer Faruk
dc.contributor.buuauthorKarkucak, Mutlu
dc.contributor.buuauthorEren, Erdal
dc.contributor.buuauthorKendall, Michaela
dc.contributor.departmentUludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.tr_TR
dc.contributor.departmentUludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.tr_TR
dc.contributor.departmentUludağ Üniversitesi/Tıp Fakültesi/Halk Sağlığı Anabilim Dalı.tr_TR
dc.contributor.orcid0000-0003-0710-5422tr_TR
dc.contributor.orcid0000-0002-1684-1053tr_TR
dc.contributor.researcheridC-7392-2019tr_TR
dc.contributor.researcheridAAM-1734-2020tr_TR
dc.contributor.scopusid8911611600tr_TR
dc.contributor.scopusid35612700100tr_TR
dc.contributor.scopusid6602802424tr_TR
dc.contributor.scopusid6505944216tr_TR
dc.contributor.scopusid6701427186tr_TR
dc.contributor.scopusid35388323500tr_TR
dc.contributor.scopusid36113153400tr_TR
dc.contributor.scopusid8062516400tr_TR
dc.date.accessioned2022-08-25T10:36:53Z
dc.date.available2022-08-25T10:36:53Z
dc.date.issued2010-11
dc.description.abstractObjective Nonsyndromic autosomal recessively inherited non-goitrous congenital hypothyroidism (CHNG) can be caused by mutations in TSHR, PAX8, TSHB and NKX2-5. We aimed to investigate mutational frequencies of these genes and genotype/phenotype correlations in consanguineous families with CHNG. Design Because consanguinity in individuals with a presumptive genetic condition is often an indicator of an autosomal recessive inheritance and allows firmer correlations to be established between genotype and phenotype, we planned to execute our study in consanguineous families. Patients Hundred and thirty-nine children with CHNG phenotype born to consanguineous families. Measurements First, we investigated cases for evidence of linkage to the four known CHNG genes by microsatellite marker analysis. Mutation analysis by direct sequencing was then performed in those cases in whom linkage to the relevant candidate gene could not be excluded. In addition, in silico analysis of the predicted structural effects of TSHR mutations was performed and related to the mutation-specific disease phenotype. Results Homozygous germline TSHR mutations were detected in six families (5%), but no mutations were detected in PAX8, TSHB and NKX2-5. Four of TSHR mutations had not previously been described. Genotype-phenotype correlations were established and found to be related to the predicted structural effects of the mutations. Conclusions Known causative genes account for the development of CHNG only in a minority of cases, and our cohort should provide a powerful resource to identify novel causative genes and to delineate the extent of locus heterogeneity in autosomal recessively inherited CHNG.en_US
dc.description.sponsorshipNewLifeen_US
dc.description.sponsorshipWellChilden_US
dc.description.sponsorshipWellcome Trust European Commissionen_US
dc.description.sponsorshipEuropean Commissionen_US
dc.description.sponsorshipPasteur Foundation of New Yorken_US
dc.identifier.citationCangül, H. vd. (2010). "Novel TSHR mutations in consanguineous families with congenital nongoitrous hypothyroidism". Clinical Endocrinology, 73(5), 671-677.en_US
dc.identifier.endpage677tr_TR
dc.identifier.issn0300-0664
dc.identifier.issn1365-2265
dc.identifier.issue5tr_TR
dc.identifier.pubmed20718767tr_TR
dc.identifier.scopus2-s2.0-78449277937tr_TR
dc.identifier.startpage671tr_TR
dc.identifier.urihttps://doi.org/10.1111/j.1365-2265.2010.03849.x
dc.identifier.urihttps://onlinelibrary.wiley.com/doi/10.1111/j.1365-2265.2010.03849.x
dc.identifier.urihttp://hdl.handle.net/11452/28370
dc.identifier.volume73tr_TR
dc.identifier.wos000282635000017tr_TR
dc.indexed.pubmedPubMeden_US
dc.indexed.scopusScopusen_US
dc.indexed.wosSCIEen_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.collaborationYurt içitr_TR
dc.relation.collaborationYurt dışıtr_TR
dc.relation.collaborationSanayitr_TR
dc.relation.journalClinical Endocrinologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergitr_TR
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectThyrotropin-receptoren_US
dc.subjectMolecular-cloningen_US
dc.subjectResistanceen_US
dc.subjectExpressionen_US
dc.subjectIdentificationen_US
dc.subjectEnvironmenten_US
dc.subjectRhodopsinen_US
dc.subjectHormoneen_US
dc.subjectComplexen_US
dc.subjectEndocrinology & metabolismen_US
dc.subject.emtreeFollitropinen_US
dc.subject.emtreeFollitropin receptoren_US
dc.subject.emtreeRhodopsinen_US
dc.subject.emtreeThyrotropinen_US
dc.subject.emtreeThyrotropin receptoren_US
dc.subject.emtreeTranscription factor Nkx2.5en_US
dc.subject.emtreeTranscription factor PAX8en_US
dc.subject.emtreeArticleen_US
dc.subject.emtreeAutosomal recessive inheritanceen_US
dc.subject.emtreeChilden_US
dc.subject.emtreeCongenital hypothyroidismen_US
dc.subject.emtreeConsanguinityen_US
dc.subject.emtreeGene mutationen_US
dc.subject.emtreeGenotype phenotype correlationen_US
dc.subject.emtreeHumanen_US
dc.subject.emtreeMajor clinical studyen_US
dc.subject.emtreeMicrosatellite markeren_US
dc.subject.emtreeMissense mutationen_US
dc.subject.emtreeMutational analysisen_US
dc.subject.emtreePedigreeen_US
dc.subject.emtreePriority journalen_US
dc.subject.emtreeReverse transcription polymerase chain reactionen_US
dc.subject.meshCongenital hypothyroidismen_US
dc.subject.meshConsanguinityen_US
dc.subject.meshDNA mutational analysisen_US
dc.subject.meshGreat Britainen_US
dc.subject.meshHomeodomain proteinsen_US
dc.subject.meshHumansen_US
dc.subject.meshModels, molecularen_US
dc.subject.meshMutationen_US
dc.subject.meshPaired box transcription factorsen_US
dc.subject.meshPakistanen_US
dc.subject.meshReceptors, thyrotropinen_US
dc.subject.meshThyrotropin, beta subuniten_US
dc.subject.meshTranscription factorsen_US
dc.subject.meshTurkeyen_US
dc.subject.scopusCongenital Hypothyroidism; Thyroid Dysgenesis; Newbornen_US
dc.subject.wosEndocrinology & metabolismen_US
dc.titleNovel TSHR mutations in consanguineous families with congenital nongoitrous hypothyroidismen_US
dc.typeArticle
dc.wos.quartileQ2en_US

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