We aimed to investigate possible new pathogenic variations in Turkish population by determining thyroid hormone receptor-beta (THRβ) variations in patients clinically diagnosed as having thyroid hormone resistance.
The results of eighty-two patients [F: 56 (mean age: 30.6), M: 26 (mean age: 31.1) who have been directed to our center between 08.05.2012-28.11.2016 were included in this study. The gene region of interest was amplified by PCR using the deep intronic primers covering exons 7, 8, 9, and 10 of the THRβ gene (ENT00000356447.8 transcript) and the nucleotide sequences were determined by the Sanger Sequence method. ProSeq and BioEdit softwares were used to compare patient and reference genomic nucleotide sequences.
Any variation was found in 18.3% of the patients, whereas 29.3% had single nucleotide polymorphisms. 18.3% of patients were determined to have NM_001252634.1:c.735C>T (p.Phe245=) variation that has been reported as benign SNP (rs3752874) in ClinVar database but reported as modifier variant (CM099823) for thyroid hormone resistance in Human Gene Mutation Database. In 28% of patients, pathogenic variations reported in ClinVar, HGMD, and COSMIC databases were determined. Three novel variations [NM_000461.4: c.701C>A, (p.Ala234Asp), c.737T>A (Leu246Gln), c.1024A>G (p.Lys342Glu)], which were not reported in ClinVar, HGMD, and COSMIC databases before, have been determined in five patients and in silico analysis with Mutation Taster, Polyphen tools scored these variants as pathogenic.
This is the first study in Turkish population investigating THRβ gene variations in patients clinically diagnosed as having thyroid hormone resistance. In addition, three novel pathogenic variants have been reported in this study.