Gene Amplification as a Common Cause of Inherited Thyroxine-Binding Globulin Excess

Endocrine Journal

TOMONOBU HASEGAWA⁴  YOSHIFUMI HIROOKA¹  YUICHI MORI⁵  MASATO KAYAMA⁵  PING JING⁵  KENJI FUJIEDA²  TSUYOSHI NOGIMORI³  TERUNORI MITSUMA⁵ 

[1] Department of Laboratory Medicine, Aichi Medical University;Department of Pediatrics, Hokkaido University School of Medicine;Department of Internal Medicine, Konanshowa Hospital;Division of Endocrinology and Metabolism, Tokyo Metropolitan Kiyose Children's Hospital;Fourth Department of Internal Medicine, Aichi Medical University

关键词: Gene amplification;    Inherited thyroxine-binding globulin excess;    Duplex PCR;    Fluorescence in situ hybridization (FISH);   

DOI  :  10.1507/endocrj.46.613

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(32)Cited-By(7)T4-binding globulin (TBG) is the major thyroid hormone transport protein in humans. Inherited abnormalities in the level of serum TBG have been classified as partial deficiency, complete deficiency and excess. A single nucleotide deletion or substitution in the TBG gene, located on Xq22, has been detected in partial and complete deficiencies. As for inherited TBG excess, the gene amplification has been recognized in two Japanese families recently. In this study, an additional three Japanese families, one familial (F-I) and two sporadic TBG excess (F-II, F-III), were analyzed. Serum TBG levels in hemizygous males were 73, 47 and 42μg/ml, three- to two-fold the normal value. The molecule had normal properties in terms of heat stability and isoelectric focussing pattern. The gene dosage of TBG was evaluated by coamplification with autosomal βGlobin or X-chromosomal Duchenne Muscular Dystrophy (DMD) and subsequent quantitation by HPLC. The TBG/βGlobin ratios of the affected male and female of F-I were 3.09- and 3.86-times, respectively, compared to that of the normal males. The TBG/DMD ratios were 2.93- and 2.09-times, respectively. These results are compatible with three copies of the TBG gene on the affected X-chromosome. Similarly, a twofold increase in gene dosage was demonstrated in the affected males of sporadic cases. Their mothers with normal TBG values had the same TBG gene dosage as normal females, suggesting that de novo gene duplication arose in gametes probably during meiosis. Amplification of the TBG gene was not recognized in these three families by in situ hybridization of prometaphase chromosomes. Though the mechanism remains unproved, gene amplification of TBG was considered to be a common cause for inherited TBG excess.

【 授权许可】

Unknown