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

Dang, Pingping; Xiao, Weiwei; Shan, Zhongyan; Xi, Yue; Wang, Ranran; Yu, Xiao‐Juan; Teng, Weiping; Teng, Xiaochun

doi:10.12998/wjcc.v7.i22.3887

Cited by 5 publications

(7 citation statements)

References 32 publications

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“…The TBG‐poly had been considered as a benign variant in early studies, but our conclusion seems inconsistent with the previous literature (Janssen et al, 1992). The statistical results of the serum TBG levels in the p.L303F hemizygotes were significantly lower than WT individuals ( p = 0.0002) in our subjects, which is consistent with two recent reports (Chen et al, 2020; Dang et al, 2019). The TBG levels of >13 μg/ml has been described as a cutoff between normal and abnormal.…”

Section: Discussionsupporting

confidence: 93%

“…There were no significant differences between groups in the level of TT4 ( p = 0.664) most likely due to the low sample size of this study (Figure 4c). We pooled SERPINA7 p.L303F variant and/or WT samples along with samples harboring this variant and/or wild type from previous research (Chen et al, 2020; Dang et al, 2019; Mannavola et al, 2006). The TT4 levels of p.L303F group were significantly lower than the WT group ( p = 0.0006; Table , Figure 4d).…”

Section: Resultsmentioning

confidence: 99%

“…As shown in Figure 4a, the TBG levels of p.L303F group(12.1 ± 0.7983, n = 8)was significantly lower than that of the WT group (21.5 ± 1.831, n = 4) (p = 0.0002). To test the reliability of our results, we first compared our data with that reported in the literature (Chen et al, 2020;Dang et al, 2019;Mannavola et al, 2006). PubMed articles on TBG deficiency as of June 2020 are collected.…”

Section: Decreased Levels Of Tbg Were Associated With Pl303f Variantmentioning

confidence: 99%

“…This SNP is often associated with other variants in the SERPINA7 gene, whose role is not yet defined (Bertenshaw et al,;Janssen et al, 2000;Mannavola et al, 2006;Mori et al, 1990;Su et al, 2003). Although p.L303F was previously considered to be a "benign" variant, two recent reports have shown that the serum TBG levels were lower in males with p.L303F variant compared to the normal controls (Chen et al, 2020;Dang et al, 2019). The mean TBG concentration in heterozygous females with TBG-PD is usually higher than half the normal level, and this level is intermediate between those found in affected and unaffected males.…”

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confidence: 99%

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Compound hemizygous variants in SERPINA7 gene cause thyroxine‐binding globulin deficiency

Fang

Chen

et al. 2021

Molec Gen & Gen Med

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Sub‐headingCompound hemizygous variants in SERPINA7 gene.BackgroundThyroxine‐binding globulin (TBG) is encoded by SERPINA7 (OMIM. 314200) which is located on Xq22.3. SERPINA7 variants caused TBG deficiency which does not require treatment, but the decreased thyroxine may be misdiagnosed as hypothyroidism. We discovered some variants of TBG caused by alterations that differ from previously reported.Materials and MethodsIn this study, we enrolled 32 subjects from 10 families and sequenced the SERPINA7 genes of TBG‐deficient subjects. Then, variants were analyzed to assess their effect on TBG expression and secretion. Bioinformatics database, protein structure, and dynamics simulation were used to evaluate the deleterious effects. Finally, we identified 2 novel and 4 known variants, and found 26 of 30 subjects carried the p.L303F. The DynaMut predictions indicated the variants (p.E91K, p.I92T, p.R294C, and p.L303F) exhibited decreased stability.ConclusionAnalyses revealed the p.L303F change the protein stability and flexibility, and it had an impact on the function of TBG, but when coexisted with other variants it might change the conformational structure of the protein and aggravate the damage to the protein. We speculated that the existence of a higher number of variants resulted in lower TBG secretion.

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Decreased Levels Of Tbg Were Associated With Pl303f Variantmentioning

confidence: 99%

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confidence: 99%

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Compound hemizygous variants in SERPINA7 gene cause thyroxine‐binding globulin deficiency

Fang

Chen

et al. 2021

Molec Gen & Gen Med

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“…To date, 49 mutations in the SERPINA7 gene have been reported to cause TBG deficiency [10][11][12][13][14]. In Korea, reports of TBG deficiency mainly discuss neonates and pediatric patients, and only a few mutation analyses of the SERPINA7 gene have been conducted.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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Identification of a novel mutation in thyroxine-binding globulin (TBG) gene associated with TBG-deficiency and its effect on the thyroid function

Gawandi

Jothivel

Kulkarni

2021

J Endocrinol Invest

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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

Cited by 5 publications

References 32 publications

Compound hemizygous variants in SERPINA7 gene cause thyroxine‐binding globulin deficiency

Compound hemizygous variants in SERPINA7 gene cause thyroxine‐binding globulin deficiency

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

Identification of a novel mutation in thyroxine-binding globulin (TBG) gene associated with TBG-deficiency and its effect on the thyroid function

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