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
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
复制标题
新型移码突变导致中国家庭甲状腺素结合球蛋白提前终止和甲状腺素结合球蛋白完全缺乏：病例报告
DOI：
10.12998/wjcc.v7.i22.3887
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发表时间：
2019-11-26
影响因子：
1.1
通讯作者：
Teng, Xiao-Chun
中科院分区：
文献类型：
--
作者：
Dang, Ping-Ping;Xiao, Wei-Wei;Teng, Xiao-Chun
背景：甲状腺素结合球蛋白（thyroine -binding globulin， TBG， SERPINA7基因产物）是人类甲状腺激素的主要转运体。TBG基因突变可能导致遗传性TBG缺乏症。已经有28个突变与完全性TBG缺乏症（TBG- cd）相关。我们在一个中国家庭中发现了一个新的移码突变，导致TBG蛋白和TBG- cd的早期终止。一例46岁中国男性，游离甲状腺素、游离三碘甲状腺原氨酸、促甲状腺素正常，但总甲状腺素和总三碘甲状腺原氨酸较低，血清TBG未检出，提示TBG- cd。从患者家属处采集血样，评估甲状腺功能和血清TBG。对来自外周血的基因组DNA进行测序以检测可能的TBG突变。采用定量PCR高分辨率熔融曲线分析对117名中国男性进行ttg - poly （L283F）的筛选。发现了一个新的TBG突变（p.p e135alafs *21），在1外显子插入19个核苷酸，导致TBG蛋白产物截短，导致TBG- cd。在先证者的父亲身上发现的另一个突变是一种已知的多态性，TBG-Poly （L283F）。117例东北汉族无亲缘关系男性中TBG-Poly等位基因的频率为21.37%。结论在一个中国家庭中发现了与TBG- cd表型相关的一个新的TBG基因突变。此外，21.37%的中国男性有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 (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).