Complete deficiency of thyroxine-binding globulin (TBG-CD buffalo) caused by a new nonsense mutation in the thyroxine-binding globulin gene

Gisah A. Carvalho, Roy E Weiss, Adrian O. Vladutiu, Samuel Refetoff

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Complete deficiency of thyroxine-binding globulin (TBG-CD) is defined as undetectable TBG in the serum of affected hemizygous subjects. Four distinct mutations have been identified in the TBG gene that cause this phenotype: TBG-CDJ (Japan), TBG-CD6, TBG-CD5, and TBG-CD Yonago. We report a new mutation producing TBG-CD phenotype. Five family members were studied, including two affected males with undetectable TBG in serum and two obligatory heterozygote females with borderline low values. Sequencing of the exons encoding the mature protein, adjacent introns and the promoter region, revealed differences in two nucleotides compared to the common type TBG, both located in exon 3: TGG (Trp) → TAG (Stop) at codon 280 and TTG (Leu) → TTT (Phe) at codon 283. The former mutation was not previously described and the latter is a polymorphic variant. Genotyping revealed that the two affected males had the mutant and polymorphic allele and their obligatory heterozygous mothers have each a common type and a mutant allele associated with the polymorphic variant. The mutant TBG Trp280Stop causes premature termination of translation that results in the production of a truncated protein that lacks 116 carboxyl terminal amino acids. The latter is believed to be responsible for the TBG-CD either because the aberrant protein is not secreted or because of reduced abundance of its mRNA.

Original languageEnglish (US)
Pages (from-to)161-165
Number of pages5
JournalThyroid
Volume8
Issue number2
StatePublished - 1998
Externally publishedYes

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Thyroxine-Binding Globulin
Nonsense Codon
Mutation
Exons
Alleles
Inteins
Genes
Phenotype
Terminator Codon
Heterozygote
Serum
Genetic Promoter Regions
Codon
Japan
Proteins
Nucleotides
Mothers
Amino Acids
Messenger RNA
Thyroxine-Binding Globulin Deficiency

ASJC Scopus subject areas

  • Endocrinology

Cite this

Complete deficiency of thyroxine-binding globulin (TBG-CD buffalo) caused by a new nonsense mutation in the thyroxine-binding globulin gene. / Carvalho, Gisah A.; Weiss, Roy E; Vladutiu, Adrian O.; Refetoff, Samuel.

In: Thyroid, Vol. 8, No. 2, 1998, p. 161-165.

Research output: Contribution to journalArticle

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