Publication:
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.departmentTıp Fakültesi
dc.contributor.departmentTıp Fakültesi
dc.contributor.departmentTıp Fakültesi
dc.contributor.departmentÇocuk Sağlığı ve Hastalıkları Ana Bilim Dalı
dc.contributor.departmentHalk Sağlığı Ana Bilim Dalı
dc.contributor.departmentTıbbi Genetik Ana Bilim Dalı
dc.contributor.orcid0000-0003-0710-5422
dc.contributor.orcid0000-0002-1684-1053
dc.contributor.researcheridC-7392-2019
dc.contributor.researcheridAAM-1734-2020
dc.contributor.scopusid8911611600
dc.contributor.scopusid35612700100
dc.contributor.scopusid6602802424
dc.contributor.scopusid6505944216
dc.contributor.scopusid6701427186
dc.contributor.scopusid35388323500
dc.contributor.scopusid36113153400
dc.contributor.scopusid8062516400
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.
dc.description.sponsorshipNewLife
dc.description.sponsorshipWellChild
dc.description.sponsorshipWellcome Trust European Commission
dc.description.sponsorshipEuropean Commission
dc.description.sponsorshipPasteur Foundation of New York
dc.identifier.citationCangül, H. vd. (2010). "Novel TSHR mutations in consanguineous families with congenital nongoitrous hypothyroidism". Clinical Endocrinology, 73(5), 671-677.
dc.identifier.endpage677
dc.identifier.issn0300-0664
dc.identifier.issn1365-2265
dc.identifier.issue5
dc.identifier.pubmed20718767
dc.identifier.scopus2-s2.0-78449277937
dc.identifier.startpage671
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.volume73
dc.identifier.wos000282635000017
dc.indexed.wosSCIE
dc.language.isoen
dc.publisherWiley
dc.relation.collaborationYurt içi
dc.relation.collaborationYurt dışı
dc.relation.collaborationSanayi
dc.relation.journalClinical Endocrinology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectThyrotropin-receptor
dc.subjectMolecular-cloning
dc.subjectResistance
dc.subjectExpression
dc.subjectIdentification
dc.subjectEnvironment
dc.subjectRhodopsin
dc.subjectHormone
dc.subjectComplex
dc.subjectEndocrinology & metabolism
dc.subject.emtreeFollitropin
dc.subject.emtreeFollitropin receptor
dc.subject.emtreeRhodopsin
dc.subject.emtreeThyrotropin
dc.subject.emtreeThyrotropin receptor
dc.subject.emtreeTranscription factor Nkx2.5
dc.subject.emtreeTranscription factor PAX8
dc.subject.emtreeArticle
dc.subject.emtreeAutosomal recessive inheritance
dc.subject.emtreeChild
dc.subject.emtreeCongenital hypothyroidism
dc.subject.emtreeConsanguinity
dc.subject.emtreeGene mutation
dc.subject.emtreeGenotype phenotype correlation
dc.subject.emtreeHuman
dc.subject.emtreeMajor clinical study
dc.subject.emtreeMicrosatellite marker
dc.subject.emtreeMissense mutation
dc.subject.emtreeMutational analysis
dc.subject.emtreePedigree
dc.subject.emtreePriority journal
dc.subject.emtreeReverse transcription polymerase chain reaction
dc.subject.meshCongenital hypothyroidism
dc.subject.meshConsanguinity
dc.subject.meshDNA mutational analysis
dc.subject.meshGreat Britain
dc.subject.meshHomeodomain proteins
dc.subject.meshHumans
dc.subject.meshModels, molecular
dc.subject.meshMutation
dc.subject.meshPaired box transcription factors
dc.subject.meshPakistan
dc.subject.meshReceptors, thyrotropin
dc.subject.meshThyrotropin, beta subunit
dc.subject.meshTranscription factors
dc.subject.meshTurkey
dc.subject.scopusCongenital Hypothyroidism; Thyroid Dysgenesis; Newborn
dc.subject.wosEndocrinology & metabolism
dc.titleNovel TSHR mutations in consanguineous families with congenital nongoitrous hypothyroidism
dc.typeArticle
dc.wos.quartileQ2
dspace.entity.typePublication
local.contributor.departmentTıp Fakültesi/Tıbbi Genetik Ana Bilim Dalı
local.contributor.departmentTıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Ana Bilim Dalı
local.contributor.departmentTıp Fakültesi/Halk Sağlığı Ana Bilim Dalı
local.indexed.atScopus
local.indexed.atWOS

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