Absence of Mutations in the Gene EncodingThyroid Transcription Factor-1 (TTF-1) in Patients with Thyroid Dysgenesis

Thyroid transription factor-1 (TTF-1) is a homeodomain-containing nuclear transcription factor, important in regulation of the thyroid-specific genes thyroglobulin (Tg), thyroperoxidase (TPO), and thyrotropin receptor (TSHR). TTF-1 is an early biochemical marker of thyroid differentiation, essential for thyroid development and maintenance of the thyroid differentiated state. It is possible that mutations in titfl gene encoding TTF-1 could result in failure of the thyroid gland to develop. Single strand conformation polymorphism (SSCP) was used to detect the presence of titfl gene mutation in a group of 15 patients with congenital hypothyroidism. The etiology of the congenital hypothyroidism included thyroid agenesis (9), sublingual ectopie thyroid (4), and severe hypoplasia (2). The analysis did not identify any titfl gene mutation, among these patients. These results rule out the presence of titfl mutations, at least in the coding region, in our thyroid dysgenesis patients. Mutations in titfl coding region may be an extremely rare event, and was not detected in our small sample size or, alternatively, such a mutant might even be viable since TTF-1 plays an important role in lung, brain, and pituitary development.