Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism.
Authors
Cangul, Hakan
Liao, Xiao-Hui
Kero, Jukka
Barone, Sharon
Srichomkwun, Panudda
Iwayama, Hideyuki
Serra, Eva G
Saglam, Halil
Eren, Erdal
Tarim, Omer
Nicholas, Adeline K
Zvetkova, Ilona
Anderson, Carl A
Frankl, Fiona E Karet
Boelaert, Kristien
Ojaniemi, Marja
Jääskeläinen, Jarmo
Patyra, Konrad
Löf, Christoffer
Williams, E Dillwyn
UK10K Consortium
Soleimani, Manoocher
Barrett, Timothy
Maher, Eamonn R
Chatterjee, V Krishna
Refetoff, Samuel
Publication Date
2018-10-18Journal Title
JCI Insight
ISSN
2379-3708
Publisher
American Society for Clinical Investigation
Volume
3
Issue
20
Language
eng
Type
Article
Physical Medium
Electronic
Metadata
Show full item recordCitation
Cangul, H., Liao, X., Schoenmakers, E., Kero, J., Barone, S., Srichomkwun, P., Iwayama, H., et al. (2018). Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism.. JCI Insight, 3 (20) https://doi.org/10.1172/jci.insight.99631
Abstract
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.
Keywords
UK10K Consortium, Thyroid Gland, Animals, Mice, Knockout, Humans, Mice, Goiter, Antiporters, Codon, Nonsense, Pedigree, DNA Mutational Analysis, Homozygote, Adult, Middle Aged, Child, Child, Preschool, Congenital Hypothyroidism, Female, Male, HEK293 Cells, Whole Exome Sequencing, Sulfate Transporters
Sponsorship
Wellcome Trust (100574/Z/12/Z)
Wellcome Trust (100585/Z/12/Z)
Wellcome Trust (095564/Z/11/Z)
Medical Research Council (G0502115)
Medical Research Council (G0600717)
Medical Research Council (MC_UU_12012/5)
Wellcome Trust (091310/Z/10/Z)
MRC (MC_UU_00014/5)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.1172/jci.insight.99631
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286298
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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