title: Mutation screening of the thyroid peroxidase gene in a cohort of 55 Portuguese patients with congenital hypothyroidism.
abstract: OBJECTIVE
  Defects in the human thyroid peroxidase (TPO) gene are reported to be one of the causes of congenital hypothyroidism (CH) due to a total iodide organification defect. The aim of the present study was to determine the nature and frequency of TPO gene mutations in patients with CH, characterised by elevated TSH levels and orthotopic thyroid gland, identified in the Portuguese National Neonatal Screening Programme.
  
  
  METHODS
  The sample comprised 55 patients, from 53 unrelated families, with follow-up in the endocrinology clinics of the treatment centres of Porto and Lisbon. Mutation screening in the TPO gene (exons 1-17) was performed by single-strand conformational analysis followed by sequencing of fragments with abnormal migration patterns.
  
  
  RESULTS
  Eight different mutations were detected in 13 patients (seven homozygotes and six compound heterozygotes). Novel mutations included three missense mutations, namely 391T > C (S131P), 1274A > G (N425S) and 2512T > A (C838S), as well as the predictable splice mutation 2748G > A (Q916Q/spl?). The undocumented polymorphism 180-47A > C was also detected.
  
  
  CONCLUSIONS
  The results are in accordance with previous observations confirming the genetic heterogeneity of TPO defects. The proportion of patients in which the aetiology was determined justifies the implementation of this molecular testing in our CH patients with dyshormonogenesis.
authors.affiliation: Unidade de Genética Molecular, Instituto de Genética Médica Jacinto Magalhães, Prãa Pedro Nunes 88, 4099-028 Porto, Portugal.
authors.forename: Carina
authors.initials: C
authors.lastname: Rodrigues
authors.forename: Paula
authors.initials: P
authors.lastname: Jorge
authors.forename: José Pires
authors.initials: JP
authors.lastname: Soares
authors.forename: Isaura
authors.initials: I
authors.lastname: Santos
authors.forename: Regina
authors.initials: R
authors.lastname: Salomão
authors.forename: Manuela
authors.initials: M
authors.lastname: Madeira
authors.forename: Rui Vaz
authors.initials: RV
authors.lastname: Osorió
authors.forename: Rosário
authors.initials: R
authors.lastname: Santos
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003409:Congenital Hypothyroidism; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics*; D007453:Iodide Peroxidase / Q000235:genetics*; D008297:Male; D010375:Pedigree; D011174:Portugal; D013972:Thyrotropin / Q000097:blood
chemical_list: D013972:Thyrotropin; D007453:Iodide Peroxidase