2. Academic Validation
  3. 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

  • Mol Cell Endocrinol. 2020 Apr 15;506:110761. doi: 10.1016/j.mce.2020.110761.
Rui-Jia Zhang 1,  Feng Sun 1,  Feng Chen 2,  Ya Fang 1,  Chen-Yan Yan 1,  Chang-Run Zhang 1,  Ying-Xia Ying 1,  Zheng Wang 1,  Cao-Xu Zhang 1,  Feng-Yao Wu 1,  Bing Han 1,  Jun Liang 3,  Shuang-Xia Zhao 1,  Huai-Dong Song 4
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Laboratory Medicine, Fujian Children's Hospital, Fujian Provincial Maternity and Children's Hospital, Fuzhou, 350001, China.
  • 3 Department of Endocrinology, The Central Hospital of Xuzhou Affiliated to Xuzhou Medical College, Xuzhou, Jiangsu Province 221109, China.
  • 4 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. Electronic address: huaidong_s1966@163.com.
PMID: 32088313 DOI: 10.1016/j.mce.2020.110761
Abstract

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.

Keywords

Congenital hypothyroidism; Genotype-phenotype analysis; Next-generation sequencing; Thyroid peroxidase.

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