A novel missense mutation (g106r) in thyroid stimulating hormone β-subunit gene in patients with central congenital hypothyroidism

Seyedeh fatemeh Talebi,1,* Mohammad mehdi heidari,2 Mehri khatami,3

1. Department of Biology, Faculty of science, Yazd University, Yazd, Iran
2. Department of Biology, Faculty of science, Yazd University, Yazd, Iran
3. Department of Biology, Faculty of science, Yazd University, Yazd, Iran



Background: central congenital hypothyroidism (cch) is a rare and evades diagnosis on thyroid stimulating hormone (tsh)-based congenital hypothyroidism (ch) screening programs in iran. cch resulting from deficient tsh secretion is much less common, being present in only 1 in 20,000–50,000 newborns. since cch is the most common preventable cause of mental retardation, an early diagnosis prompting immediate initiation of thyroid hormone replacement therapy is desirable. the aim of present study was to assess the association between tshβ mutations and patients with cch in iran population.


Methods: the study was conducted in 35 unrelated patients, diagnosed with central congenital hypothyroidism and all of them were diagnosed according to the clinical presentations of thyroid disorder. mutational screening of the exon 3 tshβ coding sequence was performed in a cohort of pediatric patients by polymerase chain reaction-single strand conformation polymorphism (pcr-sscp) and dna sequencing. in brief, the samples showing altered electrophoretic patterns of dna in the sscp gel were sent for dna sequencing to identify the exact nucleotide variation. furthermore, we analyzed effect of mutations on the structure of the protein by using pymol software and expasy database.


Results: in the present study, we report a new mutation (g106r) in exon 3 of the tshβ gene in three cases with cch. results from pymol software demonstrate that the this mutation caused to increasing the number of polar bonds in the protein structure. in addition, expasy predicts that hydrophobicity in mutant protein has reduced.


Conclusion: this mutation is probably related to cch. infants who are clinically suspected of having cch should be evaluated thoroughly, even if their tsh-based screening result is normal. computational biology tools have advantages and disadvantages, and their results are predictions that require confirmation. the effect of this nucleotide substitution in exon 3 of the tshβ gene and their role on remains to be determined.


Key words: central congenital hypothyroidism, mental retardation, tshβ, mutation