title: Screening of PAX8 mutations in Chinese patients with congenital hypothyroidism.
abstract: BACKGROUND
  Congenital hypothyroidism (CH) is a neonatal endocrine disease with an incidence of 1:2000 to 1:4000 worldwide. In about 85% of patients CH is secondary to thyroid dysgenesis, but its pathogenesis remains unclear. Thyroid transcription factors, such as paired box transcription factor 8 (PAX8), play an important role in thyroid organogenesis and development.
  
  
  OBJECTIVE
  To screen PAX8 mutations in Chinese CH patients and characterize the features of PAX8 mutations in China.
  
  
  METHODS
  Blood samples were collected from 300 CH patients in Shandong Province, China, and genomic DNA was extracted from peripheral blood leukocytes. Using PCR and direct sequencing, exon 3 and exon 4 of PAX8 were analyzed.
  
  
  RESULTS
  Analysis of PAX8 in 300 CH patients revealed heterozygous missense mutations or variations in two unrelated patients; one was a known missense mutation G92A, resulting in an arginine to histidine substitution at codon 31, the other was a missense variation G122T, resulting in the substitution of a glycine at position 41 by a valine residue. The patient with the R31H mutation had CH with thyroid hypoplasia, while the patient with the G41V variation had CH with a eutopic and normal-sized thyroid gland.
  
  
  CONCLUSIONS
  We report a heterozygous missense mutation and a variation in PAX8 in two out of 300 unrelated Chinese CH patients, showing that the PAX8 mutation rate is very low in CH patients in China.
authors.affiliation: Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, China.
authors.forename: S G
authors.initials: SG
authors.lastname: Liu
authors.forename: S S
authors.initials: SS
authors.lastname: Zhang
authors.forename: L Q
authors.initials: LQ
authors.lastname: Zhang
authors.forename: W J
authors.initials: WJ
authors.lastname: Li
authors.forename: A Q
authors.initials: AQ
authors.lastname: Zhang
authors.forename: K N
authors.initials: KN
authors.lastname: Lu
authors.forename: M J
authors.initials: MJ
authors.lastname: Wang
authors.forename: S L
authors.initials: SL
authors.lastname: Yan
authors.forename: X
authors.initials: X
authors.lastname: Ma
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D015153:Blotting, Western; D003409:Congenital Hypothyroidism / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D004247:DNA