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

Abstract

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 titf1 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 titf1 gene mutation in a group of 15 patients with congenital hypothyroidism. The etiology of the congenital hypothyroidism included thyroid agenesis (9), sublingual ectopic thyroid (4), and severe hypoplasia (2). The analysis did not identify any titf1 gene mutation, among these patients. These results rule out the presence of titf1 mutations, at least in the coding region, in our thyroid dysgenesis patients. Mutations in titf1 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.

The Key Role of Newborn Thyroid Scintigraphy With Isotopic Iodide (123I) in Defining and Managing Congenital Hypothyroidism

“…Recent studies have described multiple genetic abnormalities associated with CH. [8][9][10][11][12] In a study of DNA from patients with permanent and transient CH, Moreno et al 12 analyzed mutation in the genes for thyroid oxidase 1 (THOX1) and 2 (THOX2) and found that biallelic inactivating mutations in the THOX2 gene were associated with permanent CH and that monoallelic mutations were associated with transient CH. Sunthornthepvarakul et al 8 described 3 siblings with CH that was associated with mutations in the thyrotropin receptor gene; and after finding a similar case, Biebermann et al 9 concluded that mutation of this gene may be the cause of a substantial number of cases of CH.…”

“…5,6 We report results of thyroid scintigraphy using 123 I or technetium Tc 99m pertechnetate in 210 infants with CH diagnosed during the 24-year period from 1978 through 2002; these cases include 63 previously reported cases 7 ), which we believe support the clinical value of this imaging procedure, particularly when 123 I is used. Additionally, recent discovery of gene abnormalities in CH and in thyroid embryogenesis 2,[8][9][10][11][12][13][14][15][16] suggests that combining results of 123 I thyroid scintigraphy and results of genetic studies may facilitate characterization of the genetic mechanisms of CH.…”

Brain–lung–thyroid Syndrome

“…Авторы пришли к выводу, что NKX2-1-мутации не являются частой причиной врожден-ного гипотиреоза. Тем не менее частота NKX2-1-мутаций может быть выше у пациентов с врожденным гипотире-озом, ассоциированным с неврологической патологией и заболеваниями дыхательных путей [16][17][18][19]. В недавнем европейском исследовании у 2 из 150 детей с врожденным гипотиреозом были обнаружены мутации гена NKX2-1.…”

Novos aspectos da genética e dos mecanismos moleculares da morfogênese da tiróide para o entendimento da disgenesia tiroidiana

“…Os rastreamentos de mutação do TITF1 em populações de pacientes com DT apresentaram resultados negativos (30)(31)(32). Dada a importância fundamental deste gene nas morfogêneses pulmonar e cerebral, observada no modelo animal knockout, presume-se que a mutação inativadora em homozigose seria praticamente incompatível com a sobrevivência no período neonatal.…”