Department of Molecular Diagnostics & Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Department of Laboratory Medicine, Fujian Children's Hospital, Fujian Provincial Maternity and Children's Hospital, Fuzhou, 350001, China.
Mol Cell Endocrinol. 2020 Apr 15;506:110761. doi: 10.1016/j.mce.2020.110761. Epub 2020 Feb 20.
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 15 TPO sites, including 6 novel mutations, were identified in 230 Chinese patients with CH. The enzyme activity of the mutations in TPO was investigated in 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% TPO activity 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 of TPO was correlated with clinical phenotypes of CH patients with TPO biallelic mutations.
甲状腺激素生物合成的先天性缺陷导致中国近一半的先天性甲状腺功能减退症（CH）病例。甲状腺过氧化物酶（TPO）突变是导致甲状腺激素生成障碍的最常见突变之一。在这项研究中，在 230 名 CH 中国患者中鉴定出 15 个 TPO 位点的 35 个非同义突变，包括 6 个新突变。在体外研究了 TPO 突变的酶活性，残余酶活性低于 15%的患者表现出严重的 CH，例如在诊断时明显增加的甲状腺刺激激素（TSH）（>100μIU/mL）和明显的甲状腺肿，并需要更高剂量的 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 患者表现为轻度 CH，即典型的儿童期，在 3 岁之前未经 L-甲状腺素治疗，且在儿童期出现肉眼可见的甲状腺肿。研究结果表明，TPO 的残余酶活性与 TPO 双等位基因突变的 CH 患者的临床表型相关。
