Research on THRβ gene mutation in a patient with thyroid hormone resistance syndrome using whole-exome sequencing
10.3760/cma.j.cn311282-20230113-00023
- VernacularTitle:全外显子测序对一例甲状腺激素抵抗综合征患者THRβ基因突变的研究
- Author:
Nulali JIAYIDA
1
;
Yueyue WAN
;
Shuangxia ZHAO
;
Huaidong SONG
Author Information
1. 上海交通大学医学院附属第九人民医院分子诊断科，中心实验室 200001
- Keywords:
Thyroid hormone resistance syndrome;
Thyroid hormone receptor β;
Heterozygous mutation
- From:
Chinese Journal of Endocrinology and Metabolism
2023;39(4):353-357
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To assess clinical and genetic features in a patient with thyroid hormone resistance syndrome(RTH) and explore the pathogenic mechanism.Methods:The clinical data of the proband was collected. The genomic DNA was extracted from peripheral blood samples of the patients. The pathogenic variant was identified using whole-exome sequencing and confirmed by Sanger sequencing. Then the function of the mutation sites was detected by bioinformatics.Results:The patient presented with chest distress, palpitation, and persistent atrial fibrillation, along with elevated levels of serum free triiodothyronine(FT 3), free thyroxine(FT 4), and thyroid stimulating hormone(TSH), which suggested RTH clinically. The genetic analysis identified a heterozygous mutant of THRβ(c.1313G>A) gene at exon 8, which was a missense mutation causing the substitution of arginine to histidine at 438 position of the protein(p.R438H). Its inheritance pattern was unknown. This mutation was considered as a new one that had not been reported. Conclusion:A novel pathogenic THRβ gene mutation was found in the patient with RTH, which might be the cause of this disease. This variant c. 1313G>A is located in the ligand binding domain of THRβ, which might result in low protein activity.
