Genetic study of TSHR, PAX8 and NKX2-5 genes in Tunisian patients with congenital hypothyroidism

Abstract

Introduction Thyroid dysgenesis is reported to be associated to mutations in TSHR, PAX8 and NKX2-5 genes. In fact, mutation in TSHR gene is responsible for non-syndromic thyroid dysgenesis while mutations in PAX8 and NKX2-5 generate thyroid dysgenesis, which could be associated to renal abnormality and congenital heart disease respectively. Patients and methods The aim of the current study is to present the clinical features of eleven Tunisian patients with congenital hypothyroidism and thyroid dysgenesis, and to search for mutations or variants in TSHR, PAX8 and NKX2-5 genes. The clinical, molecular and bioinformatics investigation were performed in the eleven recruited patients. Results According to clinical data, eight patients were diagnosed with non-syndromic thyroid dysgenesis and three Tunisian patients with syndromic thyroid dysgenesis. The mutational analyses of the three candidate genes showed only known polymorphisms and we noticed that polymorphisms in PAX8 and NKX2-5 genes are especially associated with syndromic thyroid dysgenesis in our patients. Bioinformatic tools showed the putative impact of the identified polymorphisms on ESE elements and on mRNA structure. Conclusions The obtained results are suggestive of potential effects of the described polymorphisms on thyroid dysgenesis in our studied patients and are highlighted the utility of the bioinformatics tools.