title: High prevalence of DUOX2 mutations in Japanese patients with permanent congenital hypothyroidism or transient hypothyroidism.
abstract: BACKGROUND
  Dual oxidase 2 (DUOX2) mutations are a cause of dyshormonogenesis (DH) and have been identified in patients with permanent congenital hypothyroidism (PH) and with transient hypothyroidism (TH). We aimed to elucidate the prevalence and phenotypical variations of DUOX2 mutations.
  
  
  METHODS
  Forty-eight Japanese DH patients were enroled and analysed for sequence variants of DUOX2, DUOXA2, and TPO using polymerase chain reaction-amplified direct sequencing.
  
  
  RESULTS
  Fourteen sequence variants of DUOX2, including 10 novel variants, were identified in 11 patients. DUOX2 variants were more prevalent (11/48, 22.9%) than TPO (3/48, 6.3%) (p=0.020). The prevalence of DUOX2 variants in TH was slightly, but not significantly, higher than in PH. Furthermore, one patient had digenic heterozygous sequence variants of both DUOX2 and TPO.
  
  
  CONCLUSIONS
  Our results suggest that DUOX2 mutations might be the most common cause of both PH and TH, and that phenotypes of these mutations might be milder than those of other causes.
authors.forename: Kumihiro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tanahashi
authors.forename: Tokuo
authors.initials: T
authors.lastname: Mukai
authors.forename: Shigeru
authors.initials: S
authors.lastname: Suzuki
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tajima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Azuma
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujieda
mesh_terms: D019943:Amino Acid Substitution; D001324:Autoantigens / Q000235:genetics; D015331:Cohort Studies; D003409:Congenital Hypothyroidism / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D000074623:Dual Oxidases; D005260:Female; D017353:Gene Deletion; D006785:Hospitals, University; D006801:Humans; D007037:Hypothyroidism / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D007231:Infant, Newborn; D007453:Iodide Peroxidase / Q000235:genetics; D033862:Iron-Binding Proteins / Q000235:genetics; D007564:Japan / Q000453:epidemiology; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D019255:NADPH Oxidases / Q000235:genetics*; D015997:Neonatal Screening; D015995:Prevalence; D012017:Referral and Consultation; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013961:Thyroid Gland / Q000503:physiopathology*
chemical_list: D001324:Autoantigens; D033862:Iron-Binding Proteins; D000074623:Dual Oxidases; C056658:TPO protein, human; D007453:Iodide Peroxidase; D019255:NADPH Oxidases; C431515:DUOX2 protein, human