Abstract: Objective To investigate the clinical characteristics and TG gene variation characteristics of congenital hypothyroidism (CH) families with increased thyroglobulin (TG). Methods The clinical data and TG gene test results of a CH family with elevated TG were retrospectively analyzed and relevant domestic and foreign literature was reviewed. Results The proband, a 45 -day-old girl, suffered from delayed resolution of jaundice and constipation. The thyroid function test indicated CH, and the level of TG was increased. The genetic results showed compound heterozygous mutations of c.2149 C>T and c.5401+113 A>G in the TG gene of the children. Sanger sequencing confirmed that c. 2149 C>T was from father and c. 5401 + 113 A>G was from mother, and a heterozygous mutation of c. 5401 + 113 A>G was carried by his elder brother. The phenotypes of his elder brother and parents were normal. The mutations of c. 2149 C>T and c. 5401 + 113 A>G have not been reported in the literature, and these two variants were classified as likely pathogenic and unknown clinical significance according to the American genetic variation classification standards and guidelines. Conclusions It was confirmed that TG gene mutations caused an increase in TG levels in CH patients, and two new TG gene mutation sites were found.

Key words: congenital hypothyroidism; TG gene; gene mutation; high serum TG level