Department of Medical Genetics, Istanbul Medipol University, International School of Medicine, Istanbul, Turkey.
Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
JCI Insight. 2018 Oct 18;3(20):99631. doi: 10.1172/jci.insight.99631.
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.
基因介导的甲状腺激素生物合成缺陷导致先天性甲状腺功能减退症（CH）。在这里，我们报道了 6 个无关家族中 SLC26A7 的纯合截断突变与甲状腺肿性 CH 有关，并表明 SLC26A7 基因缺失的小鼠也会发生甲状腺肿性甲状腺功能减退症。在这两种物种中，该基因主要在甲状腺中表达，功能丧失与碘用于甲状腺激素合成的可用性受损有关，在小鼠中通过碘补充部分纠正。SLC26A7 是 SLC26A4（pendrin）的同一转运体家族的成员，pendrin 是一种对碘和氯（等）具有亲和力的阴离子交换器，其基因突变导致先天性耳聋和甲状腺肿性甲状腺功能减退症。然而，与 pendrin 不同，SLC26A7 不介导细胞内碘的流出，受影响个体的听力正常。我们描述了 SLC26A7 在甲状腺激素生物合成中以前未被认识的作用，其机制尚不清楚。
