title: Novel genetic variants in the TPO gene cause congenital hypothyroidism.
abstract: BACKGROUND
  Mutations in the dual oxidase maturation factor 2 (DUOXA2) and thyroid peroxidase (TPO) genes have been reported to cause goitrous congenital hypothyroidism (GCH). The aim of this study was to determine the genetic basis of GCH in affected children.
  
  
  METHODS
  Thirty children with GCH were enrolled for molecular analysis of the DUOXA2 and TPO genes. All subjects underwent clinical examination and laboratory testing. Genomic DNA was extracted from peripheral blood leukocytes, and Sanger sequencing was used to screen for DUOXA2 and TPO gene mutations in the exon fragments amplified from the extracted DNA. Family members of those patients with mutations were also enrolled and evaluated.
  
  
  RESULTS
  Analysis of the TPO gene revealed six genetic variants, including two novel heterozygous mutations, c.1970T> C (p.I657T) and c.2665G> T (p.G889X), and four mutations that have been reported previously (c.670_672del, c.2268dup, c.2266T> C and c.2647C> T). Three patients harbored the same mutation c.2268dup. The germline mutations from four unrelated families were consistent with an autosomal recessive inheritance pattern. Conversely, no mutations in the DUOXA2 gene were detected.
  
  
  CONCLUSIONS
  Two novel inactivating mutations (c.1970T> C and c.2665G> T) in the TPO gene were identified. The c.2268dup mutation occurred frequently. No mutations in the DUOXA2 gene were detected in this study.
authors.affiliation: a Department of Endocrinology and Metabolism , Huai'an Hospital Affiliated to Xuzhou Medical College and Huai'an Second People's Hospital , Huai'an , China.
authors.forename: Shao-Gang
authors.initials: SG
authors.lastname: Ma
authors.affiliation: b Department of Neonatal Screening and Care , Women and Children's Hospital of Suqian , Suqian , China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Qiu
authors.affiliation: c Department of Endocrinology and Metabolism , Suqian People's Hospital, Nanjing Drum Tower Hospital , Suqian , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: a Department of Endocrinology and Metabolism , Huai'an Hospital Affiliated to Xuzhou Medical College and Huai'an Second People's Hospital , Huai'an , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: a Department of Endocrinology and Metabolism , Huai'an Hospital Affiliated to Xuzhou Medical College and Huai'an Second People's Hospital , Huai'an , China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: a Department of Endocrinology and Metabolism , Huai'an Hospital Affiliated to Xuzhou Medical College and Huai'an Second People's Hospital , Huai'an , China.
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Ji
mesh_terms: D001324:Autoantigens / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003409:Congenital Hypothyroidism / Q000201:enzymology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics*; D033862:Iron-Binding Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D010375:Pedigree
chemical_list: D001324:Autoantigens; C513411:DUOXA2 protein, human; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; C056658:TPO protein, human; D007453:Iodide Peroxidase
keywords: Congenital hypothyroidism; dual oxidase maturation factor 2; mutation; thyroid peroxidase