A Novel Mutation (del 1711 G) in the TBG Gene as a Cause of Complete TBG Deficiency

Objective: Inherited thyroxine-binding globulin (TBG) deficiency is caused by mutations in the TBG gene (locus: Xq22.2), which result in defective synthesis or changes in the physical properties or biological function of a protein. Design: We report a novel mutation of the TBG gene causing a complete TBG deficiency in three brothers of Polish origin. DNA was extracted from all of the family members and subjected to sequence analysis. We analyzed the family with a heterozygous mother, a normal father, their three hemizygous affected sons, and their two normal sons. Main outcome: Our studies revealed a novel mutation, a single nucleotide deletion (guanine) at position 1711, codon 201 (Asp) in exon 2 (GAC → AC). This mutation led to a frame shift and premature termination at codon 206, causing a short TBG protein of 205 amino acids (AA) compared to 395 AA of the normal TBG. This new TBG-CD variant was found in the mother and her three affected sons. Conclusion: This is a new variant of TBG-CD (TBG-CD-PL Poland) containing 205 AA.