Authors: L Santarpia M Valenzise G Di Pasquale T Arrigo G San Martino M P Cicciò F Trimarchi F De Luca S Benvenga
Publish Date: 2014/04/11
Volume: 30, Issue: 1, Pages: 13-19
Abstract
Thyroid transcription factor2 TTF2/FOXE1 is a polyalanine domain protein that regulates thyroid embryogenesis but very few patients with permanent primary congenital hypothyroidism pCH harbor germline mutations of this or other transcription factors that are involved in thyroid development that might explain the etiology of pCH Variations within the polyalanine tract are found in a variety of genes and are often reported in association with malformation syndromes pCH is frequently associated with thyroid malformations and extrathyroidal malformations Therefore in this study we investigated whether alanine Ala length polymorphisms and nonpolymorphic mutations of the TTF2 gene in pCH patients might be involved in the pathogenesis of pCH The entire coding region of the TTF2 gene was analyzed in 57 Sicilian patients and 142 healthy controls We found that the homozygous Ala14 polymorphism Ala14/14 was less frequent in the pCH group than in the controls In contrast significantly more pCH patients than controls harbored the Ala16 polymorphism Ala16/16 and Ala14/16 However neither the Ala14/14 nor the Ala16 polymorphism was related to extrathyroidal malformations Two of the 57 patients carried Ala11/14 and Ala12/14 and one Ala14/14 patient also had the silent polymorphism 387 C/T Leu129Leu Other than known polymorphic variants we found no mutation in the TTF2 gene Therefore this study demonstrates that mutations in the TTF2 gene are rare in pCH patients and suggests that variations in the length of the Alatract could at least partially explain the etiology of pCH but not that of extrathyroidal malformations
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