The TPO mutation screening and genotype-phenotype analysis in 230 Chinese patients with congenital hypothyroidism.
The TPO mutation screening and genotype-phenotype analysis in 230 Chinese patients with congenital hypothyroidism.
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230例中国先天性甲状腺功能减退症患者TPO突变筛查及基因型-表型分析
DOI：
10.1016/j.mce.2020.110761
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发表时间：
2020
影响因子：
4.1
通讯作者：
Song Huai-Dong
中科院分区：
文献类型：
--
作者：
Zhang Rui-Jia;Sun Feng;Chen Feng;Fang Ya;Yan Chen-Yan;Zhang Chang-Run;Ying Ying-Xia;Wang Zheng;Zhang Cao-Xu;Wu Feng-Yao;Han Bing;Liang Jun;Zhao Shuang-Xia;Song Huai-Dong
在中国，近一半的先天性甲状腺功能减退症（CH）病例是由先天性甲状腺激素生物合成缺陷造成的。甲状腺过氧化物酶（TPO）突变是导致甲状腺激素生成异常的最常见突变之一。在这项研究中，在 230 名中国 CH 患者中鉴定出 15 个 TPO 位点的 35 个非同义突变，其中包括 6 个新突变。在体外研究了TPO突变的酶活性，残留酶活性低于15%的患者表现出严重的CH，例如诊断时促甲状腺激素（TSH）显着升高（>100 μIU/mL）和明显的甲状腺肿，需要更高剂量的L-甲状腺素来维持甲状腺功能正常。然而，TPO 活性大于 16% 的 CH 患者表现出轻度 CH，这是典型的 3 岁前未接受 L-甲状腺素治疗的儿童期社交症状，并且在儿童期出现肉眼可见的甲状腺肿。研究结果表明，TPO 的残留酶活性与 TPO 双等位基因突变的 CH 患者的临床表型相关。
Inborn defects in thyroid hormone biosynthesis contribute to nearly half of congenital hypothyroidism (CH) cases in China. The thyroid peroxidase (TPO) mutation is one of the most frequent mutations that results in thyroid dyshormonogenesis. In this study, 35 non-synonymous mutations in 15TPOsites, including 6 novel mutations, were identified in 230 Chinese patients with CH. The enzyme activity of the mutations inTPOwas investigatedin vitro, and patients with less than 15% residual enzyme activity showed severe CH, such as markedly increased thyroid-stimulating hormone (TSH) at diagnosis (>100 μIU/mL) and pronounced goiter, and required a higher dose of L-thyroxine to maintain the euthyroid. However, CH patients with greater than 16%TPOactivity showed mild CH, a typical childhood socially without L-thyroxine treatment before 3 years of age, and the appearance of a macroscopic goiter at childhood. The findings indicated that the residual enzymatic activity ofTPOwas correlated with clinical phenotypes of CH patients withTPObiallelic mutations.