title: Two novel mutations in the gene encoding thyroxine-binding globulin (TBG) as a cause of complete TBG deficiency in Taiwan.
abstract: OBJECTIVE
  Thyroxine-binding globulin (TBG) encoded by the TBG gene on chromosome Xq22 is the major transport protein, carrying approximately 75% of circulating T4. Inherited defects in TBG are associated with three phenotypes based on the level of TBG in serum of affected hemizygous males: complete TBG deficiency (TBG-CD), partial TBG deficiency (TBG-PD) and TBG excess (TBG-E). In this study, we report two unrelated Han Chinese males with complete TBG deficiency who carry different mutations in the TBG gene.
  
  
  METHODS
  Two index cases of Han males who were diagnosed as having TBG deficiency on the basis of undetectable serum TBG and an additional 75 (50 males and 25 females) normal Han Chinese.
  
  
  METHODS
  Serum thyroid hormones were measured by chemiluminescent immunoassay, thyroid autoantibodies by an agglutination test, and TSH receptor antibody and TBG by radioimmunoassay. Genomic DNA extraction, polymerase chain reaction (PCR) and DNA sequence analysis of the TBG gene were performed with standard methods.
  
  
  RESULTS
  One index case had one missense mutation in his copy of the gene, a G --> A transition in codon 52 that results in the replacement of serine by asparagine, and a known polymorphism in codon 283 (TTG --> TTt) that results in the replacement of leucine by phenylalanine. The allelic frequency of TBG-Poly allele in 75 normal Han Chinese (100 chromosomes) was 31%. A second index case was hemizygous for a nonsense mutation in codon 280 of exon 3 (TGG --> TGa). This mutation, located in the C-terminal of TBG, predicts a markedly truncated protein.
  
  
  CONCLUSIONS
  This is the first report of complete thyroxine-binding globulin deficiency (TBG-CDT1 and TBG-CDT2) due to TBG gene mutations in Taiwan.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Ching-Chieh
authors.initials: CC
authors.lastname: Su
authors.forename: Yi-Chi
authors.initials: YC
authors.lastname: Wu
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Chiu
authors.forename: Justin Ging-Shing
authors.initials: JG
authors.lastname: Won
authors.forename: Tjin-Shing
authors.initials: TS
authors.lastname: Jap
mesh_terms: D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D018389:Codon, Nonsense; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; D013624:Taiwan; D013975:Thyroxine-Binding Proteins / Q000172:deficiency* / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D013975:Thyroxine-Binding Proteins