Identifying the thyroglobulin mutations from patients with congenital hypothyroidism / 中华内分泌代谢杂志

ABSTRACT

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.