Identification of heterozygote mutations in exon 1 of nkx2.1 gene in patients with congenital hypothyroidism

Seyed ali Madani manshadi,1,* Mohammad mehdi heidari,2 Mehri khatami,3

1. Yazd University
2. Yazd University
3. Yazd University



Introduction: congenital hypothyroidism (ch) is a most common congenital endocrine disorder, affecting 1 in 3000 to 4000 newborns. congenital hypothyroidism (ch) is defined as thyroid hormone deficiency present at birth. thyroid hormone deficiency at birth is most commonly caused by a problem with thyroid gland development (dysgenesis) or a disorder of thyroid hormone biosynthesis (dyshormonogenesis). nkx2.1 (thyroid transcription factor-1; also known as ttf-1) is an essential homeodomain-containing transcription factor for the morphogenesis and differentiation of the various tissues such as thyroid, lung and ventral forebrain. ttf-1 controls the expression of select genes in the thyroid, lung and the central nervous system.


Methods: analysis of relationship between nkx2.1 gene mutations and congenital hypothyroidism was performed using pcr and single-stranded conformational polymorphism technique and dna sequencing in 35 patients and 25 control subjects. furthermore, we analyzed mutation effect on the protein structure using pymol software, sift and psipred database.


Results: in the present study, we report a new mutation (s26g) in exon 1 of the nkx2.1 gene in one cases with congenital hypothyroidism. results from pymol software demonstrate that this mutation caused to disappear hydrogen bonds between amino acids in the protein structure. the results of sift predict scores equal 0 and the results obtained from psipred shows the change in the secondary structure of the protein


Conclusion: this mutation is probably related to ch. infants who are clinically suspected of having ch should be evaluated thoroughly. computational biology tools have advantages and disadvantages, and their results are predictions that require confirmation.


Congenital hypothyroidism, nkx2.1, mutation, structure prediction