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
SN - 2379-3708
VL - 3
JO - JCI Insight
JF - JCI Insight
IS - 20
M1 - e99631
ER -