中国新生儿筛查诊断先天性甲状腺功能减退症的临床、生化特征及基因型-表型分析。
Clinical, biochemical characteristics and genotype-phenotype analysis of congenital hypothyroidism diagnosed by newborn screening in China.
机构信息
Department of Genetics and Metabolism, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Department of Genetics and Metabolism, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
出版信息
Clin Chim Acta. 2023 Jul 1;547:117459. doi: 10.1016/j.cca.2023.117459. Epub 2023 Jun 28.
BACKGROUND
Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder worldwide. However, the underlying etiology remains unclear in most patients.
METHODS
The newborn screening was performed for TSH in dried blood spots. Serum TSH, T3, T4, free T3(FT3) and free T4 (FT4) were detected for the recalled children. High-throughput sequencing were applied to detect 29 known CH genes. The statistical analyses were performed to analyze the differences between biochemical data, thyroid volume, clinical prognosis and genetic results for 97 patients who had one or more variants in CH related genes.
RESULTS
DUOX2 gene had the highest variant rate, followed by TG, TPO and TSHR gene. The "DUOX2 biallelic variants" group was associated with "Goiter", while "DUOX2 monoallelic variants" group was associated with "Agenesis". In addition, the TSH levels and initial L-T4 dose were significantly higher in "TPO biallelic variants" group than those in "DUOX2 and TSHR biallelic variants" groups.
CONCLUSIONS
Our study showed dyshormonogenesis (DH) might be the leading pathophysiology of CH in Chinese populations. DUOX2 gene mostly caused goiter, but also could be associated with hypoplasia. TPO might play a more irreplaceable role than DUOX2. The digenic variants combination indicated the complexity of genetic etiology in CH.
背景
先天性甲状腺功能减退症（CH）是全球最常见的新生儿内分泌疾病。然而，在大多数患者中，其根本病因仍不清楚。
方法
对干血斑进行 TSH 新生儿筛查。对召回的儿童检测血清 TSH、T3、T4、游离 T3（FT3）和游离 T4（FT4）。应用高通量测序检测 29 个已知的 CH 基因。对 97 例 CH 相关基因存在 1 个或多个变异的患者的生化数据、甲状腺体积、临床预后和遗传结果进行分析，以分析差异。
结果
DUOX2 基因的变异率最高，其次是 TG、TPO 和 TSHR 基因。“DUOX2 双等位基因变异”组与“甲状腺肿”相关，而“DUOX2 单等位基因变异”组与“发育不全”相关。此外，“TPO 双等位基因变异”组的 TSH 水平和初始 L-T4 剂量明显高于“DUOX2 和 TSHR 双等位基因变异”组。
结论
我们的研究表明，甲状腺功能障碍（DH）可能是中国人群 CH 的主要发病机制。DUOX2 基因主要引起甲状腺肿，但也可能与发育不全有关。TPO 可能比 DUOX2 发挥更不可替代的作用。双基因变异组合表明 CH 的遗传病因复杂。
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