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XB-ART-3595
J Clin Endocrinol Metab May 1, 2004; 89 (5): 2477-83.
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Partial deficiency of thyroxine-binding globulin-Allentown is due to a mutation in the signal peptide.

Fingerhut A , Reutrakul S , Knuedeler SD , Moeller LC , Greenlee C , Refetoff S , Janssen OE .


Abstract
We present an unusual variant of T(4)-binding globulin (TBG) found in a family from Allentown, Pennsylvania (TBG-AT). The heterozygous proposita presented serum total T(4) and TBG levels ranging from low to normal. TBG gene sequencing revealed a C-to-T substitution in codon -2 (CAC to TAC) leading to the substitution of the normal histidine by a tyrosine within the signal peptide. No mutation within the mature peptide was found. Allele-specific PCR confirmed the H(-2)Y mutation in the propositas mother and son. T(4)-binding analysis of TBG in serum from the proposita and son showed normal affinity but reduced capacity when compared with the unaffected father. Heat stability and isoelectric focusing of TBG-AT were normal. In vitro expression of a recombinant TBG-AT in Xenopus oocytes revealed a diminished secretory efficiency and confirmed the normal binding affinity and heat stability of the small amount of secreted TBG-AT. This study has defined impaired cotranslational processing as a hitherto unrecognized cause of hereditary TBG deficiency.

PubMed ID: 15126580
Article link: J Clin Endocrinol Metab
Grant support: [+]

Species referenced: Xenopus
Genes referenced: slc25a20 slc25a20.2