van Mullem Alies A, Visser Theo J, Peeters Robin P
Department of Internal Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Eur Thyroid J. 2014 Mar;3(1):17-24. doi: 10.1159/000360637. Epub 2014 Mar 14.
Thyroid hormone (TH) exerts its biological activity via the TH receptors TRα1 and TRβ1/2, which are encoded by the THRA and THRB genes. The first patients with mutations in THRB were identified decades ago. These patients had a clinical syndrome of resistance to TH associated with high serum TH and nonsuppressed thyroid-stimulating hormone levels. Until recently, no patients with mutations in THRA had been identified. In an attempt to predict the clinical phenotype of such patients, different TRα1 mutant mouse models have been generated. These mice have a variable phenotype depending on the location and severity of the mutation. Recently, the first humans with mutations in THRA were identified. Their phenotype consists of relatively low serum T4 and high serum T3 levels (and thus an elevated T3/T4 ratio), growth retardation, delayed mental and bone development, and constipation. While, in retrospect, certain features present in humans can also be found in mouse models, the first humans carrying a defect in TRα1 were not suspected of having a THRA gene mutation initially. The current review focuses on the clinical consequences of TRα1 mutations.
甲状腺激素（TH）通过TH受体TRα1和TRβ1/2发挥其生物学活性，这两种受体由THRA和THRB基因编码。数十年前就已鉴定出首批THRB基因突变的患者。这些患者患有对TH抵抗的临床综合征，伴有高血清TH和未被抑制的促甲状腺激素水平。直到最近，尚未鉴定出THRA基因突变的患者。为了预测此类患者的临床表型，已构建了不同的TRα1突变小鼠模型。这些小鼠的表型因突变的位置和严重程度而异。最近，鉴定出了首批THRA基因突变的人类患者。他们的表型包括相对较低的血清T4和较高的血清T3水平（因此T3/T4比值升高）、生长发育迟缓、智力和骨骼发育延迟以及便秘。虽然回顾起来，人类中存在的某些特征在小鼠模型中也能发现，但最初携带TRα1缺陷的首批人类并未被怀疑患有THRA基因突变。本综述重点关注TRα1突变的临床后果。
