Sequence of a variant thyroxine-binding globulin (TBG) in a family with partial TBG deficiency in Japanese (TBG-PDJ).

Thyroxine-binding globulin (TBG) is the major transport protein of thyroid hormones in human serum. In this communication, we present a sequence abnormality of the TBG-gene in a Japanese family manifesting partial TBG deficiency (TBG-PDJ). The propositus was a male with a reduced concentration of TBG (3.2μg/ml). Thyroid function tests suggested that the inheritance of this TBG abnormality was X-linked. The TBG exhibited increased heat-lability compared with the common type TBG (TBG-C). The isoelectric focusing pattern of this TBG molecule was indistinguishable from TBG-C. Genomic DNAs from white blood cells of four members of a TBG-PDJ family were subjected to polymerase chain reaction (PCR), and the products were sequenced. The sequencing of the entire coding exons and exon/intron junctions of TBG allele of the propositus revealed a single nucleotide substitution: CCT (proline) to CTT (leucine) at amino acid 363 of the TBG-C. The heterozygosity as revealed by the direct sequencing of the PCR product correlated with the TBG concentration in serum. The proline to leucine substitution may cause a change in the TBG tertiary structure and result in decreased heat stability, resulting in decreased TBG levels in the affected subjects.