Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism
Hakan Cangul, … , Samuel Refetoff, Nadia Schoenmakers
Hakan Cangul, … , Samuel Refetoff, Nadia Schoenmakers
Published October 18, 2018
Citation Information: JCI Insight. 2018;3(20):e99631. https://doi.org/10.1172/jci.insight.99631.
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Research Article Endocrinology Genetics

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

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.

Authors

Hakan Cangul, Xiao-Hui Liao, Erik Schoenmakers, Jukka Kero, Sharon Barone, Panudda Srichomkwun, Hideyuki Iwayama, Eva G. Serra, Halil Saglam, Erdal Eren, Omer Tarim, Adeline K. Nicholas, Ilona Zvetkova, Carl A. Anderson, Fiona E. Karet Frankl, Kristien Boelaert, Marja Ojaniemi, Jarmo Jääskeläinen, Konrad Patyra, Christoffer Löf, E. Dillwyn Williams, UK10K Consortium, Manoocher Soleimani, Timothy Barrett, Eamonn R. Maher, V. Krishna Chatterjee, Samuel Refetoff, Nadia Schoenmakers

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Figure 4

Intrathyroidal hormone measurements in male Slc26a7-null mice.

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Intrathyroidal hormone measurements in male Slc26a7-null mice. Box-and-w...
Box-and-whisker plots for intrathyroidal TG-bound and free (F) T4 and T3 levels in male wild-type (WT, white) and homozygous Slc26a7-null mice (KO, stippled black) age 90 days. Boxes extend from the 25th to 75th percentiles, the horizontal line represents the median, and the vertical bars represent the minimum and maximum values. Measurements were made from 6–10 mice of each genotype. P values were calculated using an unpaired 2-tailed Student’s t test. ***P < 0.0005.