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 language | English (US) |
|---|---|
| Pages (from-to) | 161-165 |
| Number of pages | 5 |
| Journal | Thyroid |
| Volume | 8 |
| Issue number | 2 |
| State | Published - 1998 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Complete deficiency of thyroxine-binding globulin (TBG-CD buffalo) caused by a new nonsense mutation in the thyroxine-binding globulin gene
AU - Carvalho, Gisah A.
AU - Weiss, Roy E
AU - Vladutiu, Adrian O.
AU - Refetoff, Samuel
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0031952921&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031952921&partnerID=8YFLogxK
M3 - Article
C2 - 9510125
AN - SCOPUS:0031952921
VL - 8
SP - 161
EP - 165
JO - Thyroid
JF - Thyroid
SN - 1050-7256
IS - 2
ER -