Potential Mutations of Thyroid Peroxidase Gene in Children with Congenital Hypothyroidism in Isfahan Province

Congenital hypothyroidism (CH), the most common congenital endocrine disorder in childhood and one of the causes of mental retardation, may be caused by defects in the enzymatic cascade of thyroid hormone synthesis, called thyroid dyshormonogenesis, of which thyroid peroxidase gene (TPO) mutations are one of the most common causes. The aim of this study was to assess frequency of TPO gene defects in patients with thyroid dyshormonogenesis in Isfahan province.

This was a cross sectional study conducted on 40 patients with permanent congenital hypothyroidism, due to thyroid dyshormonogenesis. Genomic DNA was extracted from the peripheral blood of these patients, using the salting out method. The 17 exonic region of the TPO gene was amplified and mutation screening was performed by single-strand conformational analysis (SSCP) and sequencing.

Results demonstrated one missense mutation in the (G2669A) location of exon 15 in one patient and seven different single nucleotide polymorphisms (SNPs) in exons 1, 7, 8, 11 and 15 of the TPO gene.

Frequency of TPO gene mutation in this study was lower in comparison to other similar studies. It remains possible that in these patients, the disorder was caused by a TPO gene defect in regulatory or intronic regions. In addition, methods besides SSCP analysis and detection of other gene defects in thyroid dyshormonogenesis need to be further investigated in this field.