Novel THRB mutation analysis in congenital hypothyroidism with thyroid dysgenesis. Issue 11 (3rd August 2018)

• Record Type: Journal Article
• Authors: Zhou, Zhixia; Yang, Chengyu; Lv, Fuyan; Liu, Wenmiao; Yan, Shengli; Zang, Hongwei; Li, Miaomiao; Wang, Fang; Zang, Yucui; Liu, Shiguo
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 11(2018)
• Page Start: 9474
• Page End: 9482
• Publication Date: 2018-08-03
• Subjects: apoptosis -- congenital hypothyroidism -- THRB mutation; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.27264
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Thyroid dysgenesis (TD) accounts for most cases of congenital hypothyroidism. Although mutations in thyroid hormone receptor β ( THRB ) have been identified in TD, the mutational spectrum of THRB and phenotype‐genotype correlations have not been fully elucidated. In this study, we aimed to find mutations of THRB, examine the functions of these mutations, and attempt to elucidate the relationship between THRB and TD. Thus, we screened the exons of THRB in 280 patients with TD and 200 normal subjects in samples collected from China. We performed cell morphology assays, MTT assays, flow cytometric analyses, and a quantitative reverse‐transcription polymerase chain reaction in human thyroid follicular epithelial cells (Nthy‐ori cell line) to examine the impact of THRB mutations. In two unrelated patients, two novel missense mutations, c.76G>A (p.D26N) and c.107G>A (p.C36Y), were identified in THRB . Functional studies suggested that the C36Y mutant caused changes in morphology, inhibiting cell proliferation and promoting apoptosis in a human thyroid cell line. In addition, we found that messenger RNA expressions of thyroglobulin ( TG ) and the Na + /I − symporter ( NIS ) were decreased in a time‐dependent manner in mutant THRB compared with the wild type. To our knowledge, this is the first study to document the prevalence of THRB mutations and the genotype‐phenotype spectrum of TD in a Chinese population. We characterized the function of a C36Y mutation, which reduced cell proliferation and increased cell death in thyroid epithelial cells. This study provides further evidence for genetic THRB defects and disease mechanisms in TD. Abstract : Our work is the first to document the prevalence of thyroid hormone receptor β mutations and the genotype‐phenotype spectrum of thyroid dysgenesis in a Chinese population. We identified two novel mutations and attempted to identify the effects of the mutation.