title: DUOX2 Mutations Are Frequently Associated With Congenital Hypothyroidism in the Korean Population.
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.
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, Seoul Clinical Laboratories, Seoul Medical Science Institute, Seoul, Korea.
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, Seoul Clinical Laboratories, Seoul Medical Science Institute, Seoul, Korea.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Seoul Clinical Laboratories, Seoul Medical Science Institute, Seoul, Korea.
authors.forename: Kyoung-Ryul
authors.initials: KR
authors.lastname: Lee
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: June-Hee
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hyung-Doo
authors.initials: HD
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.|Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. kimjw@skku.edu.
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
mesh_terms: D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003409:Congenital Hypothyroidism / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000074623:Dual Oxidases; D005091:Exons; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea / Q000453:epidemiology; D017422:Sequence Analysis, DNA; D013972:Thyrotropin / Q000097:blood
chemical_list: D013972:Thyrotropin; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C431515:DUOX2 protein, human
keywords: Congenital hypothyroidism; DUOX2; Incidence; Mutation; Newborn screening