Ann Lab Med.  2016 Mar;36(2):145-153. 10.3343/alm.2016.36.2.145.

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

Affiliations
  • 1Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea. kimjw@skku.edu
  • 2Department of Laboratory Medicine, Seoul Clinical Laboratories, Seoul Medical Science Institute, Seoul, Korea.
  • 3Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
  • 4Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Abstract

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.

Keyword

Congenital hypothyroidism; Newborn screening; Incidence; Mutation; DUOX2

MeSH Terms

Asian Continental Ancestry Group/*genetics
Child
Child, Preschool
Congenital Hypothyroidism/epidemiology/*genetics/pathology
Exons
Female
Genetic Association Studies
Genotype
Humans
Infant
Infant, Newborn
Male
NADPH Oxidase/*genetics
Polymorphism, Single Nucleotide
Republic of Korea/epidemiology
Sequence Analysis, DNA
Thyrotropin/blood
NADPH Oxidase
Thyrotropin

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