title: Two Novel Mutations in the Serpina7 Gene Are Associated with Complete Deficiency of Thyroxine-Binding Globulin.
abstract: BACKGROUND
  Thyroxine-binding globulin (TBG) is the main transport protein for T4 in blood. Until now, 22 mutations leading to complete TBG deficiency (TBG-CD) have been reported.
  
  
  OBJECTIVE
  We report two mutations associated with TBG-CD found in patients from Andrews, S.C., USA (TBG-CD-Andrews), and Berlin, Germany (TBG-CD-Berlin).
  
  
  METHODS
  Automated chemiluminescence immunoassays were used for the determination of TSH, free and total T4 and T3 (fT4, TT4, TT3) and TBG. Direct DNA sequencing was used to identify the TBG mutations in the propositi.
  
  
  RESULTS
  TBG-CD-Andrews was found in a 1-month-old boy who was euthyroid with normal TSH and fT4, but reduced TT4, indicating TBG deficiency. TBG was not detectable, confirming TBG-CD. No mutation in the coding region and the promoter of the TBG gene was found, but a single nucleotide substitution in intron 1 disrupts the donor splice site of exon 0 (IVS1+2T>C). Another mutation was found in an 11-year-old boy. He was also euthyroid with normal fT4 and TSH. However, TT4 and TT3 were low, suggesting TBG-CD. Sequencing revealed a 79-nucleotide deletion, ranging from intron 3 into exon 3.
  
  
  CONCLUSIONS
  We report two novel mutations of the TBG gene associated with TBG-CD. Whereas most TBG-CDs are caused by small deletions, in TBG-CD-Andrews the disruption of a donor splice site was detected, whilst in TBG-CD-Berlin the largest deletion in the Serpina7 gene to date was found.
authors.affiliation: Department of Endocrinology and Metabolism, University of Duisburg-Essen, Essen, Germany.
authors.forename: Lars C
authors.initials: LC
authors.lastname: Moeller
authors.affiliation: Medical University of South Carolina, Charleston, S.C., USA.
authors.forename: Yaw
authors.initials: Y
authors.lastname: Appiagyei-Dankah
authors.affiliation: Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Köhler
authors.affiliation: Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Biebermann
authors.affiliation: Department of Endocrinology and Metabolism, University of Duisburg-Essen, Essen, Germany.
authors.forename: Onno E
authors.initials: OE
authors.lastname: Janssen
authors.affiliation: Department of Endocrinology and Metabolism, University of Duisburg-Essen, Essen, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Führer
keywords: Serpina7; Thyroid; Thyroxine; Thyroxine-binding globulin