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.

Objective:This study aimed to identify mutations of the thyroglobulin(TG) gene and inheritance patterns in Chinese patients with congenital hypothyroidism.Methods:Clinical data of 235 children with congenital hypothyroidism and some of their families were collected from 2014 to 2018, and peripheral blood samples were collected for DNA extraction. Genomic DNA was extracted from the peripheral blood and TG gene was amplified with primers designed for each exon region and exon-intron junction region. Next generation sequencing technology and bioinformatics analysis were used to obtain TG gene mutations, followed by validation through Sanger sequencing. In addition, two compound heterozygotes with TG mutations and their parents were tested by Sanger sequencing.Results:Among 235 patients with congenital hypothyroidism, thirty-four cases(14.47%) carried TG gene variants, of which 6 cases(2.55%) carried compound heterozygous mutations. In addition, one of these TG gene variants was a hotspot mutation(T1620M was carried by four patients), nine were novel mutations(T601M, V2423I, R2308S, C2005R, C2264F, L987R, K1645Efs*49, F311Lfs*91, and T1416M).Conclusion:The mutation rate of the TG gene is higher in Chinese patients with congenital hypothyroidism, and two pedigrees indicated an autosomal recessive inheritance pattern.