The c.63A>G polymorphism in the NKX2.5 gene is associated with thyroid hypoplasia in children with thyroid dysgenesis

To search for genetic alteration in NKX2.5 gene in patients presenting both congenital heart disease (CHD) and TD. Individual phenotypes were carefully analyzed in 86 children with thyroid dysgenesis (TD) using thyroid function tests, scintigraphy, ultrasound and echocardiography. DNA was extracted and NKX2.5 gene coding region was amplified by polymerase chain reaction (PCR) and sequenced. CHD were found in 8.1% of patients with TD. The mutation screening revealed two known polymorphisms in patients with isolated TD or TD associated with CHD. None of them are predicted to result in codon change in conserved domain. The c.63A>G polymorphism was detected in 54/86 patients (49 with isolated TD and 5 with TD combined with CHD). There was a significant association of c.63A>G polymorphism with hypoplasia (p < 0.036). The c.541G>A polymorphism was observed in only one patient with isolated thyroid hypoplasia. NKX2.5 mutations were not found. The c.63A>G polymorphism might be associated with thyroid hypoplasia.