Thyroglobulin (TG) gene variants in cases with congenital goiter.

Objective: To evaluate TG gene variants and their effects on the clinical course of the disease in children with congenital hypothyroidism (CH) who are suspected to have thyroglobulin synthesis defect.

Methods: The study was carried out in patients who were suspected to have thyroglobulin synthesis defect due to low serum thyroglobulin level and goiter at the time of diagnosis of CH. Peripheral blood samples were taken and hypothyroidism gene panel including 344 genes was amplified by PCR and sequenced using next-generation DNA sequencing (NGS) method.

Results: A total of four eligible cases were identified for genetic analysis, and variants were detected in all of them. In case 1, a previously reported homozygous c.638 + 5 G>A splice site variant was detected. In case 2, compound heterozygous variants including a previously reported nonsense variant c.7111 C>T, (p.Arg2371Ter) on the first allele and a novel nonsense variant c.5748 C>A, (p.Tyr1916Ter) on the second allele were detected. In case 3, a previously reported homozygous nonsense variant c.1888 C>T, (p.Gln630Ter) was detected. In case 4, a novel homozygous intronic variant c.6200-25T>G was detected.

Conclusion: The distinctive phenotypic features of TG gene variants, which are one of the rare causes of dyshormonogenesis, provide an advantage in diagnosis. Therefore, we recommend genetic analysis in cases with low thyroglobulin levels and goiter. Our findings support that TG variants show a heterogeneous distribution over the whole gene. Since the relationship between TG gene variants and thyroid cancer, we suggest that clarification of TG gene variants is important in terms of early diagnosis of thyroid nodule and malignancy.