Sequence of a Variant Thyroxine-Binding Globulin (TBG) in a Family with Partial TBG Deficiency in Japanese (TBG-PDJ)

Endocrine Journal

EIICHI KINOSHITA²  YUICHI MORI³  HISAO SEO¹  IKUO YAMAMORI³  YOSHIYUKI TANI³  MASAAKI YOSHIMOTO²  YOSHIHARU MURATA¹  YOSHITAKA MIURA³  YUTAKA OISO³  TADASHI MATSUMOTO² 

[1] Department of Endocrinology and Metabolism, Research Institute of Environmental Medicine, Nagoya University;Department of Pediatrics, Nagasaki University School of Medicine;First Department of Internal Medicine, Nagoya University School of Medicine

关键词: Partial TBG deficiency;    PCR;    Sequencing analysis;   

DOI  :  10.1507/endocrj.40.127

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(20)Cited-By(4)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.

【 授权许可】

Unknown