Congenital goitrous hypothyroidism is caused by dysfunction of the iodide transporter SLC26A7

概要

Iodide transport and storage in the thyroid follicles is crucial for thyroid hormone synthesis. the iodide importer, also known as the sodium/iodide symporter (NIS,SLC5A5), which transports iodide from circulating blood to follicular cells; and the iodide exporter, also known as pendrin (SLC26A4), which transports iodide from the follicular cells to the lumen. Although patients with Pendred syndrome carry biallelic loss-of-function mutations in the pendrin gene SLC26A4 and are characterised by congenital hypothyroidism and hearing loss, they can maintain normal thyroid hormone levels, as can Slc26a4 knockout mice. Thus, it is assumed that mammals have another iodide transporter, aside from SLC26A4. 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.1498C > 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 thethyroid and its dysfunction affects thyroid hormonogenesis in humans and causes congenital goitrous hypothyroidism.