甲状腺激素α受体（Thyroid Hormone Receptor α， THRα）
THRα基因突变会导致甲状腺激素α受体抵抗（Resistance to Thyroid Hormoneα， RTHα）（OMIM No.614450），为常染色体显性遗传疾病[57]。与RTHβ相似，RTHα患者临床表型差异较大，但主要表现与先天性甲状腺功能减退症相似，主要生化特征包括：T4轻度降低、T3稍高，T4/T3 比值低，TSH水平正常或升高。THRA基因由于选择性剪切作用，可以编码两种蛋白亚型TRα1和TRα2，两者的表达及功能有所差异。因此，THRA基因不同突变位点对于其编码两种蛋白亚型的不同影响会引起不一致的临床表型[58-59]。
1．突变仅TRα1受累：THRA基因突变只影响TRα1蛋白亚型时，患者主要的骨骼发育异常表现有生长迟缓、身材矮小、骨龄延迟、出牙晚、颅面骨发育异常（缝间骨、巨颅畸形、鼻梁扁平）、骨骺发育不良及骨骼矿化不良等，部分患者还出现耳硬化症及听力受损的症状。有研究报道T4治疗可以加速生长，但患者终身高大多仍在-2SD以下，而生长激素治疗对该疾病无效[60-61]。另有研究发现该类突变与所致疾病具有一定的基因型表型相关性，错义突变患者表型较轻，而无义突变等导致蛋白截短的突变的患者表型更重[62]。
2.突变同时累及TRα1和TRα2：有研究报道该类突变患者有类似甲状腺功能减退表现，包括生长发育障碍、颅面骨异常（巨颅畸形、鼻梁扁平、小颌畸形等）、锁骨及肋骨发育不良、脊柱侧凸、四肢短小、并指畸形等，甚至出现胎儿宫内发育迟滞并导致死亡[63]。儿童期尽早开始T4治疗可以获得较好的生长反应。该类突变患者与仅累及TRα1突变的患者相比较，其表型可能更严重[64]。
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