Spectrum of Human <i>Foxe1/TTF2</i> Mutations

Abstract

FOXE1 (or TTF-2) has been recognized as one of the thyroid dysgenesis (TD)-related genes based on its early expression at the thyroid bud stage and on the finding in Foxe1 knock-out mice of a sublingual or absent thyroid gland. In humans, three homozygous loss-of-function missense mutations located within the forkhead domain have been reported in 5 patients with Bamforth syndrome. This syndrome is a rare inherited condition whose main features are congenital hypothyroidism (CH) due to TD (usually athyreosis), cleft palate, and spiky hair, with or without choanal atresia and bifid epiglottis. These FOXE1 mutations were typically inherited from heterozygous carrier parents who were usually consanguineous. Recently, a novelmissense mutation was found in a patient with sporadic Bamforth syndrome, inherited via uniparental isodisomy. Altogether these observations strongly suggest that FOXE1 is involved in both familial and sporadic syndromic CH due to TD in association with cleft palate. Nevertheless, despite intensive research, FOXE1 mutations have been identified in only a minority of the affected patients. Recent data suggest that the transcription factor encoded by FOXE1 may act as a susceptibility factor for TD via variations in FOXE1 polyalanine tract length, which may modulate the risk of TD.

Ectopic Thyroid Tissue in the Adrenal Gland

“…However, no specific gene alterations have been associated with ETT. 7,9 Of all ETT locations, the base of the tongue around the area of the foramen cecum is the most common, and the so-called "lingual thyroid" represents up to 90% of ETT cases. 10 A lingual thyroid is often the manifestation of complete migration failure of the primitive gland during embryogenesis and it is therefore the most common form of thyroid ectopia.…”

Autoimmune thyroid disorders

“…RNASET2 is expressed in CD4+ T-helper and CD8+ T cells [23]; 4. FOXE1 is involved in thyroid gland morphogenesis and binds response elements in the thyroglobulin (Tg) and thyroid peroxidase promoters [25].…”

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

“…The phenotypic presentations vary between the patients but clinical presentations are consistent, which [34][35][36][37] WES analysis has therefore provided us with the first steps for determining the impact of these two variants of uncertain significance and whether they have the propensity to be disease causing.…”