ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P817

Five new mutations leading to partial deficiency of thyroxine-binding globulin

Lars C Moeller1, Philip Vinzelberg1, Joachim Pohlenz2, Andrea Jaeger1, Klaus Mann1 & Onno E Janssen1

1Department of Endocrinology, Universityhospital of Essen Medical School, Essen, Germany; 2Children’s Hospital of the Johannes Gutenberg University, Mainz, Germany.

Introduction: Thyroxine-binding globulin (TBG) is the main thyroid hormone transport protein in blood. So far, 26 TBG deficiency mutations have been reported, 7 of them leading to partial TBG deficiency. We examined T4 binding capacity and the TBG gene in patients with normal free T4 (fT4) and reduced total T4 (TT4). We present and characterize five new partial TBG deficiency mutations.

Methods: Automated chemiluminescence immunoassays were used for the determination of TSH, fT4, TT4 and TBG. In case of TBG deficiency, the extent of deficiency was determined by a TBG-specific T4-binding assay. Direct DNA sequencing of the TBG gene (exons 1-4 and the non-coding exon 0) was used to identify mutations in the propositi. To characterize the mutations, they were introduced into a TBG expression vector, which was then transfected into HepG2 cells. After 48 h, T4-binding capacity, representing TBG concentration, was measured in the media.

Results: T4 binding capacity in media of cells transfected with a normal TBG-vector was set as 100%. T4 binding capacity in media of cells transfected with an empty vector as a negative control was 2.6%. Five TBG mutations lead to a severe reduction of T4 binding capacity, representing partial TBG deficiency: R35Q: 11.4%; S52R: 12.4%; N112L: 12.0%; R381G: 4.8%; S382R: 10.5%.

Conclusion: Mutations in the TBG gene can lead to TBG deficiency. We report 5 new partial TBG deficiency mutations and experimentally characterized their T4 binding capacity.

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