GENETIC-BASIS OF CONGENITAL HYPOTHYROIDISM - ABNORMALITIES IN THE TSH-BETA GENE, THE PIT1 GENE, AND THE NIS GENE

We have elucidated the molecular pathology of three types of congenita l hypothyroidism. Thyrotropin (TSH) is the major regulator of thyroid function. In cases of isolated congenital TSH deficiency, we found tha t they are caused by a missense mutation in the conserved CAGYC region of the TSH beta gene. Pit-1/GHF-1 is a pituitary specific POU-domain DNA binding factor, which transactivates the growth hormone (GH), prol actin (PRL), TSH beta genes, and the PIT1 gene itself. In cases of com bined deficiency of GH, PRL, and TSH, we found that they are caused by abnormalities in the PIT1 gene, either recessively or dominantly. Sod ium dependent iodide symporter (NIS) actively transports iodide into t he thyroid cells to produce thyroid hormones. In cases of iodide trans port defect, we elucidated that a missense mutation in the transmembra ne region of the NIS gene caused them.