Novel frameshift mutation causes early termination of the thyroxine-binding globulin protein and complete thyroxine-binding globulin deficiency in a Chinese family: A case report  

作　　者：Ping-Ping Dang Wei-Wei Xiao Zhong-Yan Shan Yue Xi Ran-Ran Wang Xiao-Hui Yu Wei-Ping Teng Xiao-Chun Teng 

机构地区：[1]Department of Endocrinology and Metabolism,Institute of Endocrinology,Liaoning Provincial Key Laboratory of Endocrine Diseases,The First Hospital of China Medical University,Shenyang 110001,Liaoning Province,China [2]Department of Endocrinology and Metabolism,The Third Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000,Liaoning Province,China

出　　处：《World Journal of Clinical Cases》2019年第22期3887-3894,共8页世界临床病例杂志

基　　金：Supported by the National Natural Science Foundation of China,No.81570711;National Clinical Key College Fund and the Key Platform Foundation of Science and Technology for the Universities in Liaoning Province,No.16010

摘　　要：BACKGROUND Thyroxine-binding globulin(TBG;the gene product of SERPINA7)is the main transporter of thyroid hormones in humans.Mutations in the TBG gene may lead to inherited TBG deficiency.There have been 28 reported mutations that associate with complete TBG deficiency(TBG-CD).Here we identified a novel frameshift mutation causing early termination of the TBG protein and TBG-CD in a Chinese family.CASE SUMMARY A 46-year-old Chinese man was referred to our hospital with normal free thyroxine,free triiodothyronine,thyrotropin,but lower total thyroxine and total triiodothyronine,and undetectable serum TBG,indicative of TBG-CD.Blood samples were obtained from the patient’s family members and thyroid function and serum TBG were evaluated.Genomic DNA from peripheral blood was sequenced to detect possible TBG mutation(s).Quantitative PCR high-resolution melting curve analysis was used to screen TBG-Poly(L283F)among 117 Chinese men.A novel mutation of TBG(p.Phe135Alafs*21),a 19-nucleotide insertion in exon 1,was identified,which resulted in a truncated TBG protein product and caused TBG-CD.The other mutation,identified in the proband’s father,is a known polymorphism,TBG-Poly(L283F).The frequency of the TBG-Poly allele among 117 unrelated Han Chinese men from northeast China was 21.37%.CONCLUSION A novel mutation in the TBG gene associated with the TBG-CD phenotype was identified in a Chinese family.Additionally,it was found that 21.37%of Chinese males had TBG-Poly(L283F).BACKGROUND Thyroxine-binding globulin(TBG; the gene product of SERPINA7) is the main transporter of thyroid hormones in humans. Mutations in the TBG gene may lead to inherited TBG deficiency. There have been 28 reported mutations that associate with complete TBG deficiency(TBG-CD). Here we identified a novel frameshift mutation causing early termination of the TBG protein and TBG-CD in a Chinese family.CASE SUMMARY A 46-year-old Chinese man was referred to our hospital with normal free thyroxine, free triiodothyronine, thyrotropin, but lower total thyroxine and total triiodothyronine, and undetectable serum TBG, indicative of TBG-CD. Blood samples were obtained from the patient’s family members and thyroid function and serum TBG were evaluated. Genomic DNA from peripheral blood was sequenced to detect possible TBG mutation(s). Quantitative PCR high-resolution melting curve analysis was used to screen TBG-Poly(L283 F) among 117 Chinese men. A novel mutation of TBG(p.Phe135 Alafs*21), a 19-nucleotide insertion in exon 1, was identified, which resulted in a truncated TBG protein product and caused TBG-CD. The other mutation, identified in the proband’s father, is a known polymorphism, TBG-Poly(L283 F). The frequency of the TBG-Poly allele among 117 unrelated Han Chinese men from northeast China was 21.37%.CONCLUSION A novel mutation in the TBG gene associated with the TBG-CD phenotype was identified in a Chinese family. Additionally, it was found that 21.37% of Chinese males had TBG-Poly(L283 F).

关 键 词：Thyroxine-binding GLOBULIN COMPLETE thyroxine-binding GLOBULIN DEFICIENCY Partial thyroxine-binding GLOBULIN DEFICIENCY Gene polymorphism Case report 

分 类 号：R73[医药卫生—肿瘤]