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

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...

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Bibliographic Details
Published in:Annals of laboratory medicine 2016, 36(2), , pp.145-153
Main Authors: Park, Kyoung-Jin, Park, Hyun-Kyung, Kim, Young-Jin, Lee, Kyoung-Ryul, Park, Jong-Ho, Park, June-Hee, Park, Hyung-Doo, Lee, Soo-Youn, Kim, Jong-Won
Format: Article
Language:English
Subjects:
Asian Continental Ancestry Group - genetics
Child
Child, Preschool
Congenital Hypothyroidism - epidemiology
Congenital Hypothyroidism - genetics
Congenital Hypothyroidism - pathology
Dual Oxidases
Exons
Female
Genetic Association Studies
Genotype
Humans
Infant
Infant, Newborn
Male
NADPH Oxidases - genetics
Original
Polymorphism, Single Nucleotide
Republic of Korea - epidemiology
Sequence Analysis, DNA
Thyrotropin - blood
병리학
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Summary: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. 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. 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. 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.
ISSN:2234-3806
2234-3814
DOI:10.3343/alm.2016.36.2.145