Takeshita A, Nagayama Y, Yamashita S, Takamatsu J, Ohsawa N, Maesaka H, Tachibana K, Tokuhiro E, Ashizawa K, Yokoyama N
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Thyroid. 1994 Fall;4(3):255-9. doi: 10.1089/thy.1994.4.255.
Congenital primary hypothyroidism due to thyrotropin (TSH) unresponsiveness is a very rare disorder and only a few cases have been documented previously. To elucidate whether structural abnormalities in the TSH receptor (TSHR) could be a primary underlying mechanism of this disorder, we analyzed nucleotide sequence of the entire coding region of the TSHR gene in three patients diagnosed with congenital primary hypothyroidism associated with TSH unresponsiveness. Diagnosis of TSH unresponsiveness was largely made based on the following criteria: (a) congenital primary hypothyroidism with autosomal recessive inheritance, (b) a nongoitrous thyroid gland in a normal position with low thyroidal radioactive iodine uptake, (c) normal in vitro TSH bioactivity or absent in vivo response to exogenous TSH, and (d) absence of thyroid autoantibodies. The TSHR cDNA was successfully obtained from RNA of peripheral mononuclear leukocytes with reverse transcription and polymerase chain reaction, and was sequenced directly. Comparison of these nucleotide sequences with the normal TSHR sequence revealed no difference in the predicted amino acid sequence with a heterozygous polymorphism in codon 601 in one patient, indicating absence of TSHR structural abnormalities in these patients. Our results indicate that congenital primary hypothyroidism associated with TSH unresponsiveness is unlikely to be due to mutations in the TSHR-structure gene.
由于促甲状腺激素（TSH）无反应性导致的先天性原发性甲状腺功能减退症是一种非常罕见的疾病，此前仅有少数病例报道。为了阐明TSH受体（TSHR）的结构异常是否可能是该疾病的主要潜在机制，我们分析了3例诊断为与TSH无反应性相关的先天性原发性甲状腺功能减退症患者的TSHR基因整个编码区的核苷酸序列。TSH无反应性的诊断主要基于以下标准：（a）常染色体隐性遗传的先天性原发性甲状腺功能减退症；（b）甲状腺位置正常且无肿大，甲状腺放射性碘摄取低；（c）体外TSH生物活性正常或体内对外源性TSH无反应；（d）无甲状腺自身抗体。通过逆转录和聚合酶链反应从外周单核白细胞的RNA中成功获得TSHR cDNA，并直接进行测序。将这些核苷酸序列与正常TSHR序列进行比较，结果显示在一名患者的第601密码子处存在杂合多态性，但预测的氨基酸序列没有差异，表明这些患者不存在TSHR结构异常。我们的结果表明，与TSH无反应性相关的先天性原发性甲状腺功能减退症不太可能是由于TSHR结构基因突变所致。
