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

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Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism. / UK10K Consortium.

In: JCI Insight, Vol. 3, No. 20, e99631, 18.10.2018.

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@article{9f81f4020b534ada8cb4476d41bd6bbd,
title = "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.",
keywords = "Endocrinology, Genetics, Molecular genetics, Monogenic diseases, Thyroid disease",
author = "{UK10K Consortium} and Hakan Cangul and Xiao-hui Liao and Erik Schoenmakers and Jukka Kero and Sharon Barone and Panudda Srichomkwun and Hideyuki Iwayama and Serra, {Eva G.} and Halil Saglam and Erdal Eren and Omer Tarim and Nicholas, {Adeline K.} and Ilona Zvetkova and Anderson, {Carl A.} and Frankl, {Fiona E. Karet} and Kristien Boelaert and Marja Ojaniemi and Jarmo J{\"a}{\"a}skel{\"a}inen and Konrad Patyra and Christoffer L{\"o}f and Williams, {E. Dillwyn} and Manoocher Soleimani and Timothy Barrett and Maher, {Eamonn R.} and Chatterjee, {V. Krishna} and Samuel Refetoff and Nadia Schoenmakers",
year = "2018",
month = oct,
day = "18",
doi = "10.1172/jci.insight.99631",
language = "English",
volume = "3",
journal = "JCI Insight",
issn = "2379-3708",
publisher = "American Society for Clinical Investigation",
number = "20",

}

RIS

TY - JOUR

T1 - Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism

AU - UK10K Consortium

AU - Cangul, Hakan

AU - Liao, Xiao-hui

AU - Schoenmakers, Erik

AU - Kero, Jukka

AU - Barone, Sharon

AU - Srichomkwun, Panudda

AU - Iwayama, Hideyuki

AU - Serra, Eva G.

AU - Saglam, Halil

AU - Eren, Erdal

AU - Tarim, Omer

AU - Nicholas, Adeline K.

AU - Zvetkova, Ilona

AU - Anderson, Carl A.

AU - Frankl, Fiona E. Karet

AU - Boelaert, Kristien

AU - Ojaniemi, Marja

AU - Jääskeläinen, Jarmo

AU - Patyra, Konrad

AU - Löf, Christoffer

AU - Williams, E. Dillwyn

AU - Soleimani, Manoocher

AU - Barrett, Timothy

AU - Maher, Eamonn R.

AU - Chatterjee, V. Krishna

AU - Refetoff, Samuel

AU - Schoenmakers, Nadia

PY - 2018/10/18

Y1 - 2018/10/18

N2 - 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.

AB - 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.

KW - Endocrinology

KW - Genetics

KW - Molecular genetics

KW - Monogenic diseases

KW - Thyroid disease

U2 - 10.1172/jci.insight.99631

DO - 10.1172/jci.insight.99631

M3 - Abstract

VL - 3

JO - JCI Insight

JF - JCI Insight

SN - 2379-3708

IS - 20

M1 - e99631

ER -