Molecular Mechanisms and Pathophysiology of Congenital Hypothyroidism

点击翻译按钮获取中文摘要

(1)The prevalence on monogenic disease in Japanese congenital hypothyroidism(CH), 1.biallelic TSHR mutations ; 4.3% in moderate to severe CH, 2.PAX8 mutations ; 2.0% in CH, 3.bialelic DUOX2 mutations ; 7.8% in CH, 4.TG mutations ; 4.9% in CH, 5.TPO mutations ; 2.0% in CH, 6.Other mutations ; rare. (2)Polygenic disease; one CH patient having digenic mutations of TSHR and DUOX2. (3)In vitro experiments confirmed loss of functions of 1. four mutations of TSHR, namely G132R, A204V, D403N, R450H, having reduced binding activities and cAMP responses, and 2. K80_A84dup PAX8 localizing in nucleus, but having severely impaired DNA binding and transactivation.