title: High prevalence of thyroid peroxidase gene mutations in patients with thyroid dyshormonogenesis.
abstract: OBJECTIVE
  Thyroid dyshormonogenesis is a genetically heterogeneous group of inherited disorders in the enzymatic cascade of thyroid hormone synthesis that result in congenital hypothyroidism (CH). Thyroid peroxidase gene (TPO) mutations are one of the most common causes of thyroid dyshormonogenesis. The aim of this study was to identify TPO gene defects in a cohort of patients with thyroid dyshormonogenesis from Slovenia, Bosnia, and Slovakia.
  
  
  METHODS
  Forty-three patients with permanent CH and orthoptic thyroid glands from 39 unrelated families participated in the study. Mutational analysis of the TPO gene and part of its promoter consisted of single-stranded conformation polymorphism analysis, sequencing, and restriction fragment length polymorphism (RFLP) analysis.
  
  
  RESULTS
  TPO gene mutations were identified in 46% of participants. Seven different mutations were identified, four mutations of these being novel, namely 613C > T (R175X), 1519_1539del (A477_N483del), 2089G > A (G667S), and 2669G > A (G860R). Only a single allele mutation was identified in 65% of the TPO mutation carriers.
  
  
  CONCLUSIONS
  The results showed a higher prevalence of TPO gene mutations in thyroid dyshormonogenesis when compared with published studies. The high percentage of single allele mutations implied possible intronic or regulatory TPO gene mutations or monoallelic expression.
authors.affiliation: University Medical Centre, University Children's Hospital, Vrazov trg 1, SI-1000 Ljubljana, Slovenia.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Avbelj
authors.forename: Husref
authors.initials: H
authors.lastname: Tahirovic
authors.forename: Marusa
authors.initials: M
authors.lastname: Debeljak
authors.forename: Maria
authors.initials: M
authors.lastname: Kusekova
authors.forename: Alma
authors.initials: A
authors.lastname: Toromanovic
authors.forename: Ciril
authors.initials: C
authors.lastname: Krzisnik
authors.forename: Tadej
authors.initials: T
authors.lastname: Battelino
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics*; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D013954:Thyroglobulin / Q000097:blood; D050033:Thyroid Dysgenesis / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
chemical_list: D013972:Thyrotropin; D004247:DNA; D013954:Thyroglobulin; D007453:Iodide Peroxidase; D013974:Thyroxine