Screening of PAX8mutations in Chinese patients with congenital hypothyroidism

Background:Congenital hypothyroidism (CH) is a neonatal endocrine disease with an incidence of 1:2000 to 1:4000 worldwide. In about 85% of patients CH is secondary to thyroid dysgenesis, but its pathogenesis remains unclear. Thyroid transcription factors, such as paired box transcription factor 8 (PAX8), play an important role in thyroid organogenesis and development. Aim:To screen PAX8mutations in Chinese CH patients and characterize the features of PAX8mutations in China. Materials and methods:Blood samples were collected from 300 CH patients in Shandong Province, China, and genomic DNA was extracted from peripheral blood leukocytes. Using PCR and direct sequencing, exon 3 and exon 4 of PAX8were analyzed. Results:Analysis of PAX8 in 300 CH patients revealed heterozygous missense mutations or variations in two unrelated patients; one was a known missense mutation G92A, resulting in an arginine to histidine substitution at codon 31, the other was a missense variation G122T, resulting in the substitution of a glycine at position 41 by a valine residue. The patient with the R31H mutation had CH with thyroid hypoplasia, while the patient with the G41V variation had CH with a eutopic and normal-sized thyroid gland. Conclusion:We report a heterozygous missense mutation and a variation in PAX8 in two out of 300 unrelated Chinese CH patients, showing that the PAX8mutation rate is very low in CH patients in China.