Clinical characteristics and genetics analysis for the ITD of congenital hypothyroidism

Lifei Gong; Nan Yang; Jinqi Zhao; Yue Tang; Lulu Li; Haihe Yang; Yuanyuan Kong

doi:10.1515/jpem-2022-0052

Article

Clinical characteristics and genetics analysis for the ITD of congenital hypothyroidism

Lifei Gong , Nan Yang , Jinqi Zhao , Yue Tang , Lulu Li , Haihe Yang and Yuanyuan Kong

Published/Copyright: April 20, 2022

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 35 Issue 6

Abstract

Objectives

Iodide transport defect (ITD) is one of the principal causes of congenital hypothyroidism (CH) and its primary molecular mechanism is a mutation of the sodium/iodide symporter (NIS) gene. This study aims to analyse the clinical characteristics and genetic mutations of ITD.

Methods

The participants were a pair of siblings diagnosed with congenital hypothyroidism. Inductively coupled plasma mass spectrometry was used to determine the concentration of salivary iodine and serum iodine and to calculate their ratio. At the same time, next-generation sequencing (NGS) was applied to detect all exons of congenital hypothyroidism-related genes. All suspicious variants were further validated in the patients and their parents by PCR and Sanger sequencing.

Results

Both patients were conclusively diagnosed with thyroid iodine transport defect (ITD). NGS identified two variants of the NIS gene in the siblings: c.1021G>A (p.Gly341Arg) with paternal origin and c.1330-2A>C with maternal origin. Both of these variants have not been reported to date. They are predicted to be pathogenic based on these clinical symptoms and comprehensive software analysis.

Conclusions

This is the first reported family study of congenital hypothyroidism with SLC5A5 mutation in China. Next-generation sequencing technology is an effective means of studying the genetics of congenital hypothyroidism. The therapeutic effect of potassium iodide needs to be further evaluated.

Keywords: congenital hypothyroidism; iodide transport defect; next-generation sequencing; sodium/iodide symporter; thyroid dyshormonogenesis

Corresponding author: Yuan-yuan Kong, MD, PhD, Department of Newborn Screening Centre, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, P. R. China, Phone: +8610-52275310; +8610-52275314; Fax: +8610-85979592, E-mail: kongyuanyuan1971@mail.ccmu.edu.cn

Acknowledgments

The authors thank the participants described in this report for their consent and support to publish this manuscript.

Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The local Institutional Review Board deemed the study exempt from review.

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Received: 2022-01-28

Accepted: 2022-03-28

Published Online: 2022-04-20

Published in Print: 2022-06-27

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Articles in the same Issue

https://doi.org/10.1515/jpem-2022-0052

Keywords for this article

congenital hypothyroidism; iodide transport defect; next-generation sequencing; sodium/iodide symporter; thyroid dyshormonogenesis