Objective: To investigate thyroid-stimulating hormone receptor (TSHR) and thyroid peroxidase (TPO) mutations in Korean patients with primary congenital hypothyroidism (CH).
Context: Congenital hypothyroidism is a common genetic disorder in which the majority of mutations occur in the TSHR and TPO genes.
Design: We examined the frequencies of TSHR and TPO mutations among Korean patients with primary CH. Furthermore, we explored the relationships between imaging findings and mutation status.
Patients: A total of 193 paediatric patients with nonsyndromic CH were enrolled in the present study.
Measurements: Patients with decreased (99m) Tc uptake were screened for TSHR mutations using Sanger sequencing, and those with increased uptake were screened for TPO mutations. The relationships between scintigraphic and ultrasonographic findings and mutation status were analysed.
Results: Thirteen (16·5%) of 79 patients with decreased (99m) Tc uptake were found to harbour TSHR mutations including G132R, G245S, R450H, R519C and F525S. The R450H mutation was present in 13 (72·2%) of 18 disease alleles. Seven (10·3%) of 68 patients with increased (99m) Tc uptake harboured TPO mutations including R189Q, K439E, G493S, C808LfsX72, A863T, R875Hfs and P883S. The TSHR and TPO mutations were observed only in patients with normal to slightly enlarged thyroid glands.
Conclusions: This study identified underlying TSHR and TPO mutations in Korean patients with CH and revealed a possible relationship between imaging findings and mutation status. In addition, the low rate of mutation positivity suggests significant genetic heterogeneity of CH in the Korean population.
© 2011 Blackwell Publishing Ltd.