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dc.contributor.authorCangul, Hakan
dc.contributor.authorLiao, Xiao-Hui
dc.contributor.authorSchoenmakers, Erik
dc.contributor.authorKero, Jukka
dc.contributor.authorBarone, Sharon
dc.contributor.authorSrichomkwun, Panudda
dc.contributor.authorIwayama, Hideyuki
dc.contributor.authorSerra, Eva G
dc.contributor.authorSaglam, Halil
dc.contributor.authorEren, Erdal
dc.contributor.authorTarim, Omer
dc.contributor.authorNicholas, Adeline
dc.contributor.authorZvetkova, Ilona
dc.contributor.authorAnderson, Carl A
dc.contributor.authorKaret, Fiona
dc.contributor.authorBoelaert, Kristien
dc.contributor.authorOjaniemi, Marja
dc.contributor.authorJääskeläinen, Jarmo
dc.contributor.authorPatyra, Konrad
dc.contributor.authorLöf, Christoffer
dc.contributor.authorWilliams, E Dillwyn
dc.contributor.authorUK10K Consortium
dc.contributor.authorSoleimani, Manoocher
dc.contributor.authorBarrett, Timothy
dc.contributor.authorMaher, Eamonn
dc.contributor.authorChatterjee, Krishna
dc.contributor.authorRefetoff, Samuel
dc.contributor.authorSchoenmakers, Nadia
dc.date.accessioned2018-12-05T00:30:20Z
dc.date.available2018-12-05T00:30:20Z
dc.date.issued2018-10-18
dc.identifier.issn2379-3708
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/286298
dc.description.abstractDefects in genes mediating thyroid hormone biosynthesis result in dyshormonogenic congenital hypothyroidism (CH). Here, we report homozygous truncating mutations in SLC26A7 in 6 unrelated families with goitrous CH and show that goitrous hypothyroidism also occurs in Slc26a7-null mice. In both species, the gene is expressed predominantly in the thyroid gland, and loss of function is associated with impaired availability of iodine for thyroid hormone synthesis, partially corrected in mice by iodine supplementation. SLC26A7 is a member of the same transporter family as SLC26A4 (pendrin), an anion exchanger with affinity for iodide and chloride (among others), whose gene mutations cause congenital deafness and dyshormonogenic goiter. However, in contrast to pendrin, SLC26A7 does not mediate cellular iodide efflux and hearing in affected individuals is normal. We delineate a hitherto unrecognized role for SLC26A7 in thyroid hormone biosynthesis, for which the mechanism remains unclear.
dc.format.mediumElectronic
dc.languageeng
dc.publisherAmerican Society for Clinical Investigation
dc.subjectUK10K Consortium
dc.subjectThyroid Gland
dc.subjectAnimals
dc.subjectMice, Knockout
dc.subjectHumans
dc.subjectMice
dc.subjectGoiter
dc.subjectAntiporters
dc.subjectCodon, Nonsense
dc.subjectPedigree
dc.subjectDNA Mutational Analysis
dc.subjectHomozygote
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectChild
dc.subjectChild, Preschool
dc.subjectCongenital Hypothyroidism
dc.subjectFemale
dc.subjectMale
dc.subjectHEK293 Cells
dc.subjectWhole Exome Sequencing
dc.subjectSulfate Transporters
dc.titleHomozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism.
dc.typeArticle
prism.issueIdentifier20
prism.publicationDate2018
prism.publicationNameJCI Insight
prism.volume3
dc.identifier.doi10.17863/CAM.33608
dcterms.dateAccepted2018-09-06
rioxxterms.versionofrecord10.1172/jci.insight.99631
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.licenseref.startdate2018-10-18
dc.contributor.orcidSchoenmakers, Erik [0000-0003-0674-8282]
dc.contributor.orcidKaret, Fiona [0000-0002-2457-2869]
dc.contributor.orcidMaher, Eamonn [0000-0002-6226-6918]
dc.contributor.orcidChatterjee, Krishna [0000-0002-2654-8854]
dc.contributor.orcidSchoenmakers, Nadia [0000-0002-0847-2884]
dc.identifier.eissn2379-3708
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (100574/Z/12/Z)
pubs.funder-project-idWellcome Trust (100585/Z/12/Z)
pubs.funder-project-idWellcome Trust (095564/Z/11/Z)
pubs.funder-project-idMedical Research Council (G0502115)
pubs.funder-project-idMedical Research Council (G0600717)
pubs.funder-project-idMedical Research Council (MC_UU_12012/5)
pubs.funder-project-idWellcome Trust (091310/Z/10/Z)
pubs.funder-project-idMRC (MC_UU_00014/5)
cam.issuedOnline2018-10-18
cam.orpheus.successThu Jan 30 10:53:58 GMT 2020 - The item has an open VoR version.
rioxxterms.freetoread.startdate2100-01-01


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