RTH的THRα突变
近年来，随着第一例THRA突变病例被发现至今，显示所有THRA突变患者均是杂合子突变[31-32]。与小鼠模型的Thra 人工突变相似，THRA突变患者的循环甲状腺激素水平和反馈机制并没有显著地改变。
第一例病例被Bochukova及其同事所描述，临床上伴有线性增长和牙齿发育延迟、血清IGF-1水平降低、肌张力下降、精细运动协调受损、严重便秘。血压和心率较低，T4治疗无效，而性激素结合球蛋白水平、肝标记的TH功能升高。体外分析显示T3亲和力显著下降，TREs缺陷激活，抑制基础启动子活性，表现为明显的显性负效应。这种突变移除部分AF-2结构域，可以预测像PV突变，消除了共激活因子的相互作用。与Bochukova所描述的病例相似，THRA突变的患者均表现为相似的临床症状，身材矮小、骨龄延迟、低IGF-1、甲状腺功能减退等临床症状如皮肤干燥和反应减慢[31-32]。
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