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

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 pr...

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Bibliographic Details
Published in:Journal of molecular medicine (Berlin, Germany) Germany), 2006-10, Vol.84 (10), p.864-871
Main Authors: MANNAVOLA, Deborah, VANNUCCHI, Guia, FUGAZZOLA, Laura, CIRELLO, Valentina, CAMPI, Irene, RADETTI, Giorgio, PERSANI, Luca, REFETOFF, Samuel, BECK-PECCOZ, Paolo
Format: Article
Language:English
Subjects:
Aged
Base Sequence
Biological and medical sciences
Child
Child, Preschool
Codon, Nonsense
DNA Mutational Analysis
Exons - genetics
Female
Frameshift Mutation
General aspects
Heterozygote
Homozygote
Humans
Isoelectric Focusing
Male
Medical sciences
Middle Aged
Models, Genetic
Pedigree
Thyroxine-Binding Proteins - deficiency
Thyroxine-Binding Proteins - genetics
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Summary: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.
ISSN:0946-2716
1432-1440
DOI:10.1007/s00109-006-0078-9