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Thyroglobulin (TG) is essential for thyroid hormone synthesis, and germline TG mutations cause congenital hypothyroidism and goiter. A single case report described a 21-year-old man with congenital hypothyroidism due to compound heterozygous TG mutations (p.Gly304Cys and p.Arg432Ter) who presented with a cold thyroid nodule, although histology revealed only a hyperplastic nodule without carcinoma (PMID:22934199). In a small cohort of African American patients with radioiodine-refractory Thyroid Cancer, specific TG haplotypes (n=4) were uniquely associated with incomplete response to radioiodine therapy, but no segregation analysis or causal coding variants were identified (PMID:30654714). These limited genetic data do not establish TG as a predisposition gene for thyroid carcinoma.
Circulating TG mRNA has clinical utility as a biomarker: nested RT-PCR detection of TG transcripts achieved 83% sensitivity for residual or metastatic differentiated thyroid carcinoma in 34 post-thyroidectomy patients, outperforming serum thyroglobulin measurement and diagnostic radioiodine scans (PMID:11061512). However, mechanistic or functional studies linking TG gene variants to thyroid oncogenesis are lacking. At present, TG variant screening is not recommended for cancer risk assessment, although TG mRNA assays may aid in surveillance of disease recurrence.
Gene–Disease AssociationLimitedSingle case report without malignant findings and a small haplotype cohort (n=4) with no segregation Genetic EvidenceLimitedTG haplotypes in four radioiodine-refractory patients; no proband variant data or family segregation Functional EvidenceLimitedCirculating TG mRNA assays support biomarker use but no functional assays linking TG variants to oncogenesis |