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 (3.2 micrograms/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.
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Y
Y
Miura
Y
Y
Mori
I
I
Yamamori
Y
Y
Tani
Y
Y
Murata
M
M
Yoshimoto
E
E
Kinoshita
T
T
Matsumoto
Y
Y
Oiso
H
H
Seo
D001483:Base Sequence; D004247:DNA / Q000032:analysis; D005260:Female; D006579:Heterozygote; D006358:Hot Temperature; D006801:Humans; D007525:Isoelectric Focusing; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D013960:Thyroid Function Tests; D013963:Thyroid Hormones / Q000097:blood; D013975:Thyroxine-Binding Proteins / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*
D013963:Thyroid Hormones; D013975:Thyroxine-Binding Proteins; D004247:DNA