Congenital goitrous hypothyroidism is caused by dysfunction of the iodide transporter SLC26A7
Congenital goitrous hypothyroidism is caused by dysfunction of the iodide transporter SLC26A7
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DOI：
10.1038/s42003-019-0503-6
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发表时间：
2019-07-24
影响因子：
5.9
通讯作者：
Kamma, Hiroshi
中科院分区：
文献类型：
--
作者：
Ishii, Jun;Suzuki, Atsushi;Kamma, Hiroshi
碘在甲状腺滤泡中的运输和储存对甲状腺激素的合成至关重要。Pendrin是一种将碘转运到甲状腺滤泡的碘输出蛋白，它是Pendred综合征的原因，Pendred综合征是一种以先天性甲状腺功能减退和听力丧失为特征的疾病。然而，Pendred综合征患者的甲状腺激素水平基本正常，表明存在另一种未知的碘转运蛋白。在这里，我们表明，SLC 26 A7是一种新的碘转运蛋白在甲状腺。我们观察到SLC 26 A7在正常甲状腺组织中特异性表达，并证明其在碘转运中的功能。使用全外显子组测序，我们还发现了一个纯合的无义突变SLC 26 A7（c.1498 C > T; p.Gln500Ter）在两个同胞先天性甲状腺肿甲状腺功能减退症。突变的SLC 26 A7蛋白显示异常的细胞质定位，并且缺乏碘转运功能。这些结果表明，SLC 26 A7在甲状腺中作为一种新的碘转运蛋白发挥作用，其功能障碍影响人类甲状腺的增殖，并导致先天性甲状腺肿性甲状腺功能减退。
Iodide transport and storage in the thyroid follicles is crucial for thyroid hormone synthesis. Pendrin, the iodide exporter that transports iodide to thyroid follicles, is responsible for Pendred syndrome, a disorder characterized by congenital hypothyroidism and hearing loss. However, thyroid hormone levels are basically normal in patients with Pendred syndrome, indicating the presence of another unknown iodide transporter. Here, we show that SLC26A7 is a novel iodide transporter in the thyroid. We observe that SLC26A7 is specifically expressed in normal thyroid tissues and demonstrate its function in iodide transport. Using whole-exome sequencing, we also find a homozygous nonsense mutation in SLC26A7 (c.1498 C > T; p.Gln500Ter) in two siblings with congenital goitrous hypothyroidism. The mutated SLC26A7 protein shows an abnormal cytoplasmic localisation and lacks the iodide transport function. These results reveal that SLC26A7 functions as a novel iodide transporter in the thyroid and its dysfunction affects thyroid hormonogenesis in humans and causes congenital goitrous hypothyroidism.