title: High frequency of DUOX2 mutations in transient or permanent congenital hypothyroidism with eutopic thyroid glands.
abstract: OBJECTIVE
  This study aimed to clarify the frequency, phenotypes, and molecular spectrum of DUOX2, TPO, TSHR, and TG mutations in patients with congenital hypothyroidism (CH) with enlarged or normal-sized eutopic thyroid glands.
  
  
  METHODS
  The study cohort included 43 subjects from 41 unrelated families who had CH with eutopic thyroid glands. Mutation analyses of DUOX2, TPO, and TSHR were performed. The functional capacities of novel missense variants of DUOX2 were verified by measuring H2O2 generation in vitro.
  
  
  RESULTS
  Of the 43 subjects, 23 (53.5%) had sequence variants in at least one gene. Twelve different DUOX2 variants, including seven novel variants, were identified in 20 subjects. A functional analysis of the DUOX2 variants revealed that most variants, other than p.G206V and p.H678R, caused a significant reduction in H2O2 generation. Therefore, 15 subjects harbored functionally deleterious DUOX2 variants. Of these, 5 subjects had transient CH, and 10 were found to have permanent CH. Sequence variants in TSHR were identified in 5 subjects. One of the 43 subjects (2.3%) had sequence variants in two different genes.
  
  
  CONCLUSIONS
  DUOX2 variants are a relatively common cause of CH with normal-sized or enlarged eutopic thyroid glands. Variable phenotypes were associated with partial loss of the functional activity of DUOX2 variants.
authors.affiliation: Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Jin
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Heo
authors.forename: Yoo-Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: Gu-Hwan
authors.initials: GH
authors.lastname: Kim
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Beom-Hee
authors.initials: BH
authors.lastname: Lee
authors.forename: Han-Wook
authors.initials: HW
authors.lastname: Yoo
mesh_terms: D002675:Child, Preschool; D015331:Cohort Studies; D003409:Congenital Hypothyroidism / Q000235:genetics* / Q000473:pathology*; D000074623:Dual Oxidases; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007453:Iodide Peroxidase / Q000235:genetics; D008297:Male; D020125:Mutation, Missense; D019255:NADPH Oxidases / Q000235:genetics*; D011989:Receptors, Thyrotropin / Q000235:genetics; D013954:Thyroglobulin / Q000235:genetics; D013961:Thyroid Gland / Q000473:pathology*; D013974:Thyroxine / Q000627:therapeutic use
chemical_list: D011989:Receptors, Thyrotropin; D013954:Thyroglobulin; D000074623:Dual Oxidases; D007453:Iodide Peroxidase; D019255:NADPH Oxidases; C431515:DUOX2 protein, human; D013974:Thyroxine