Abstract

In the present study we analyzed the thyroid transcription factor-1 (TTF-1) gene in patients with congenital hypothyroidism due to thyroid dysgenesis: In Iran, a large screening program was run for almost 2 years on all newborns. In total around 300 new CH patients were found. The incidence of CH was found to be 1 in every 370 newborns, which is quite high compared to the world report (1 in every 3000–4000 newborns).

The aim of the present study was to investigate the mutation/variant of thyroid transcription factor-1 (TTF-1) genes in Iranian children with congenital hypothyroidism (CH) due to thyroid dysgenesis. Genomic DNA was isolated from peripheral blood of 40 pediatric patients. The whole TTF2 gene was amplified by PCR with 4 pairs of primers. The PCR sequence was the directly sequenced. Sequencing of the TTF-1 gene revealed the following mutations/polymorphism in patients.

We found polymorphisms such as (CTT→CTC) at position 129 in 4 patients (TAC→TAT) at position 210 in 2 patients, (TCC→TCT) at position 273 in 3 patients. Frameshift mutations were found in 1 patients including mutation in both position 215 (insertion T) and 227. Substitution mutations at position 138 (GAG→ TAT), 163 (GAC→AAC), 168 (GCA→AGC), 221(insertion A), 225 (GTT→ GCC), 239 (insertion C), 346 (GGG→ AGG), 374 (AGC→AAC) in one patient were detected. In conclusion, known polymorphisms in 9 patients (22.5%) were detected. Two frameshift and nine substitution mutations in 11 patients (27.5%) were identified.