Original Article

Ann Lab Med 2016; 36(2): 145-153

Published online March 1, 2016

Copyright © Korean Society for Laboratory Medicine.

DUOX2 Mutations Are Frequently Associated With Congenital Hypothyroidism in the Korean Population

Kyoung-Jin Park, M.D.1,*, Hyun-Kyung Park, M.D.2,*, Young-Jin Kim, M.D.2, Kyoung-Ryul Lee, M.D.2, Jong-Ho Park, B.S.1, June-Hee Park, B.S.3, Hyung-Doo Park, M.D.4, Soo-Youn Lee, M.D.4, and Jong-Won Kim, M.D.1,4

Department of Health Sciences and Technology1, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University; Department of Laboratory Medicine2, Seoul Clinical Laboratories, Seoul Medical Science Institute; Samsung Biomedical Research Institute3, Samsung Medical Center; Department of Laboratory Medicine & Genetics4, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Correspondence to: Jong-Won Kim
Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
Tel: +82-2-3410-2705
Fax: +82-2-3410-2719

*These two authors contributed equally to this work.

Received: September 20, 2015; Revised: December 2, 2015; Accepted: December 2, 2015


Background: Most cases with congenital hypothyroidism (CH) are usually sporadic, while about 20% of the cases are caused by genetic defects. Little information is available regarding the mutation incidence and genetic heterogeneity of CH in Koreans. We aimed to determine the mutation incidence of CH in newborn screenings (NBS) and to evaluate the frequency and spectrum of mutations underlying CH.
Methods: A total of 112 newborns with thyroid dysfunction were enrolled from 256,624 consecutive NBS. Furthermore, 58 outpatients with primary CH were added from an endocrine clinic. All coding exons of TSHR, PAX8, TPO, DUOX2, DUOXA2, and SCL5A5 were sequenced.
Results: The mutation incidence of CH was estimated to be 1 in 6,580 newborns. A total of 36 different mutations were identified in 53 cases. The overall mutation positive rate was 31%. The DUOX2 mutations were the most prevalent in both newborns and outpatients. Seven different recurrent mutations [p.G488R (n=13), p.A649E (n=3), p.R885Q (n=3), p.I1080T (n=2), and p.A1206T (n=2) in DUOX2; p.Y138X (n=9) in DUOXA2; and p.R450H (n=5) in TSHR) were identified as the mutations underlying CH.
Conclusions: The mutation incidence of CH was considerably higher than expected in the Korean newborn population. This study revealed seven different recurrent mutations underlying CH. We conclude that DUOX2 mutations are a frequent cause of CH in the Korean population.

Keywords: Congenital hypothyroidism, Newborn screening, Incidence, Mutation, DUOX2