Endocrinol Metab.  2022 Dec;37(6):870-878. 10.3803/EnM.2022.1591.

Identification of Mutations in the Thyroxine-Binding Globulin (TBG) Gene in Patients with TBG Deficiency in Korea

• Heo J
• Kim SM
• Ryu HJ
• Park H
• Kim TH
• Chung JH
• Park HD
• Kim SW

• KMID: 2537288
• DOI: http://doi.org/10.3803/EnM.2022.1591

Abstract

Background
Thyroxine-binding globulin (TBG) is a major transporter protein for thyroid hormones. The serpin family A member 7 (SERPINA7) gene codes for TBG, and mutations of the SERPINA7 gene result in TBG deficiency. Although more than 40 mutations have been reported in several countries, only a few studies of TBG deficiency and SERPINA7 gene mutation have been performed in Korea. The aim of this study is to review the clinical presentations and laboratory findings of patients with TBG deficiency and to investigate the types of SERPINA7 gene mutation.
Methods
Five unrelated Korean adults with TBG deficiency attending endocrinology clinic underwent SERPINA7 gene sequencing. Four patients harbored a SERPINA7 gene mutation. Serum thyroid hormones, anti-microsomal antibodies, and TBG were measured. Genomic DNA was extracted from whole blood. All exons and intron-exon boundaries of the TBG gene were amplified and sequencing was performed.
Results
Two patients were heterozygous females, and the other two were hemizygous males. One heterozygous female had coexisting hypothyroidism. The other heterozygous female was erroneously prescribed levothyroxine at a local clinic. One hemizygous male harbored a novel mutation, p.Phe269Cysfs*18, which caused TBG partial deficiency. Three patients had the p.Leu372Phefs*23 mutation, which is known as TBG-complete deficiency Japan (TBG-CDJ) and was also presented in previous mutation analyses in Korea.
Conclusion
This study presents four patients diagnosed with TBG deficiency and provides the results of SERPINA7 gene sequencing. One novel mutation, p.Phe269Cysfs*18, causing TBD-partial deficiency and three cases of TBG-CDJ were demonstrated. It is necessary to identify TBG deficiency to prevent improper treatment. Also, sequencing of the SERPINA7 gene would provide valuable information about the TBG variants in Korea.

Keyword

Thyroxine-binding globulin; SERPINA7 protein, human; Thyroxine-binding globulin deficiency; Inherited thyroxinebinding globulin deficiency

Figure

• 

  Fig. 1. Sanger sequencing chromatogram of the serpin family A member 7 (SERPINA7) variants detected in this study. (A) c.1114del variant was detected in heterozygous patient 1 and 3 and in hemizygous patient 2. (B) A novel hemizygous 2-bp deletion variant, c.806_807del, was detected in patient 4. Electropherograms of a wildtype and the proband are demonstrated. The positions of the deletion are indicated by arrows. The predicted amino acid translation is shown above the sequence. Altered codons in the proband are shown in red.

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