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JCI Insight. 2018 Oct 18;3(20). pii: 99631. doi: 10.1172/jci.insight.99631. [Epub ahead of print]

Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism.

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Department of Medical Genetics, Istanbul Medipol University, International School of Medicine, Istanbul, Turkey.
Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom (UK).
Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.
Department of Paediatrics, Turku University Hospital, Turku, Finland.
University of Cincinnati and Veterans Administration Hospital, Cincinnati, Ohio, USA.
Department of Human Genetics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
Uludag University School of Medicine, Department of Paediatric Endocrinology, Bursa, Turkey.
Department of Medical Genetics and Division of Renal Medicine, University of Cambridge, Cambridge, UK.
Institute of Metabolism and Systems Research, University of Birmingham and Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Edgbaston, Birmingham, UK.
PEDEGO Research Center and MRC Oulu, University of Oulu, and Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
Department of Pediatrics, University of Eastern Finland and Kuopio University, Hospital, Kuopio, Finland.
Thyroid Carcinogenesis Group, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham and Department of Endocrinology, Birmingham Children's Hospital, Birmingham, UK.
Department of Medical Genetics, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
Department of Pediatrics and the Committee on Genetics, The University of Chicago, Chicago, Illinois, USA.


Defects 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.


Endocrinology; Genetics; Molecular genetics; Monogenic diseases; Thyroid disease

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