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 thy roid hormones in human serum. In this communication, we present a sequ ence abnormality of the TBG-gene in a Japanese family manifesting part ial TBG deficiency (TBG-PDJ). The propositus was a male with a reduced concentration of TBG (3.2 mug/ml). Thyroid function tests suggested t hat the inheritance of this TBG abnormality was X-linked. The TBG exhi bited increased heat-lability compared with the common type TBG (TBG-C ). The isoelectric focusing pattern of this TBG molecule was indisting uishable from TBG-C. Genomic DNAs from white blood cells of four membe rs of a TBG-PDJ family were subjected to polymerase chain reaction (PC R), and the products were sequenced. The sequencing of the entire codi ng exons and exon/intron junctions of TBG allele of the propositus rev ealed 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 concentr ation 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.