TGB deficiency: Description of two novel mutations associated with complete TBG deficiency and review of the literature

Deborah Mannavola, Guia Vannucchi, Laura Fugazzola, Valentina Cirello, Irene Campi, Giorgio Radetti, Luca Persani, Samuel Refetoff, Paolo Beck-Peccoz

Research output: Contribution to journalArticle


Thyroxine-binding globulin (TBG) is the main thyroid hormone transport protein in serum. Inherited TBG defects lead to a complete (TBG-CD) or a partial (TBG-PD) deficiency and have a diagenic transmission, being clinically fully expressed only in hemizygous males and in homozygous females. In the present study, seven patients from two unrelated families with TBG-CD were studied and two novel TBG mutations were documented. In particular, a T insertion at the 5′ donor splice site of exon 0, between nucleotides 2 and 3 at the beginning of intron 1 (g.IVS1+2_3insT) was found in one family and was named TBG-Milano. The other novel mutation is a T deletion at nucleotide 214 of exon 1, which leads to a frameshift at codon 50 with a premature stop codon at position 51 (c.214delT, P50fsX51) and was named TBG-Nikita. According to the X-linked transmission of the defect, females harboring the mutation showed a reduction in TBG levels with normal TSH and total thyroid hormone values at the lower limit of normal. Males harboring either TBG-Milano or TBG-Nikita, showed normal TSH values and low levels of total thyroid hormones and lacked TBG. In conclusion, we report two novel mutations of the TBG gene associated with a complete TBG defect. The first mutation lies at the 5′ donor splice site of exon 0 and probably alters the start of translation, while the second is a single nucleotide deletion and leads to a premature stop codon.

Original languageEnglish
Pages (from-to)864-871
Number of pages8
JournalJournal of Molecular Medicine
Issue number10
Publication statusPublished - Oct 2006



  • TBG gene mutations
  • TBG-CD
  • TBG-PD
  • Thyroid hormones
  • Thyroxine-binding globulin defects

ASJC Scopus subject areas

  • Medicine(all)

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