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

Gawandi, Smita; Jothivel, K; Kulkarni, Supriya

doi:10.1007/s40618-021-01697-z

Cited by 5 publications

(5 citation statements)

References 27 publications

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“…The TBG deficiency caused by the Serpina7 gene mutation is a rare thyroid disease, which is generally acquired through X-linked recessive inheritance. 2 The proband in this study was diagnosed with TBG-PD and was found to have a missense mutation of the Serpina7 gene: C.909(exon4)G>T(P.L303F). The thyroid functions of her father, brother and sister indicated that the FT3, T3, T4 and RT3 levels decreased, with the decrease in T3 and T4 more substantial, which was consistent with the clinical phenotype of the patient.…”

Section: Discussionmentioning

confidence: 78%

“… 1 Thyroxine-binding globulin deficiency is a rare thyroid disease, mostly caused by a gene mutation, and is generally acquired through X-linked recessive inheritance. 2 The gene encoding TBG is named the Serpina 7 gene, while it is also known as the TBG gene. It is located on Xq22 2, spans 5.5 kb and contains five exons.…”

Section: Introductionmentioning

confidence: 99%

“…4 Genetic TBG defects, including changes in protein synthesis, secretion and stability, result in TBG variants. 2 Reports from different countries have described how these mutations in the coding and non-coding regions of the Serpina7 gene lead to complete deficiency (TBG-CD) and partial deficiency (TBG-PD). 5 Since the first report of the human Serpina7 gene in 1986, 6 a series of mutations and polymorphisms have been identified.…”

Section: Introductionmentioning

confidence: 99%

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Partial Thyroid Hormone-Binding Globulin Deficiency: A Case Report and Literature Review

Liu¹,

Li²,

Xiong³

et al. 2023

DMSO

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Background Thyroxine binding globulin (TBG) deficiency is a rare thyroid disease, mostly caused by genetic mutations and acquired by X-linked recessive inheritance. The clinical features of children with TBG deficiency and their family members were summarised and the Serpina7 gene mutation was analysed, providing a reference for the differentiation of TBG deficiency. Methods Thyroid function was detected in TBG deficient patients, and genetic analysis was performed using polymerase chain reaction (PCR) and direct DNA sequencing to detect the characteristics of TBG mutants. Using “thyroxine binding globulin, gene and mutation” as keywords, PubMed (biomedical literature database), Web of Science and other databases were searched for relevant studies to collect and summarise relevant information. Results The TBG (14.7 μg/mL), 70% triiodothyronine (T3) (<0.3 nmol/L), total T3 (Tr3) (<0.05 ng/mL) and thyroxine (T4) (14.72 nmol/L) values were lower than normal, while the thyrotropin (TSH) (2.33 uIU/mL), free T3 (FT3) (1.62 pmol/L), and free T4 (FT4) (11.39 pmol/L) values were normal. These values indicate a TBG partially deficient phenotype. Using PCR amplification and direct sequencing of the target gene, a missense mutation in exon 4 of the Serpina7 gene was found in the patient and the father, and the nucleic acid variant was C.909 (exon 4) g > T; the patient was heterozygous and the father was hemizygous. The literature search retrieved a total of 45 studies, most of which were related to mutations in the Serpina7 gene. The mutation locations included exons, introns, enhancers and promoters, with exons the predominant location. A total of 49 variants of the Serpina7 gene were identified. Conclusion Serpina7 C.909G (P.L303F) is a mutation acquired from the father by X-linked recessive inheritance. The main clinical features of TBG deficiency patients are low serum T4, T3 and TBG levels, normal TSH, FT3 and FT4 levels, and no clinical manifestations.

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Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Partial Thyroid Hormone-Binding Globulin Deficiency: A Case Report and Literature Review

Liu¹,

Li²,

Xiong³

et al. 2023

DMSO

View full text Add to dashboard Cite

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“…In addition, SERPINA7 can promote the differentiation and maturation of osteoblasts and enhance their bone matrix deposition ability. SERPINA7 can also inhibit the apoptosis of osteoblasts and promote bone growth and repair [55]. In summary, the four identified IUGR-HGs are involved in important processes of animal embryogenesis and fetal organ development in the maternal uterus.…”

Section: Discussionmentioning

confidence: 95%

Four Markers Useful for the Distinction of Intrauterine Growth Restriction in Sheep

Wang,

Chen,

Qiao

et al. 2023

Animals

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Intrauterine growth restriction (IUGR) is a common perinatal complication in animal reproduction, with long-lasting negative effects on neonates and postnatal animals, which seriously negatively affects livestock production. In this study, we aimed to identify potential genes associated with the diagnosis of IUGR through bioinformatics analysis. Based on the 73 differentially expressed related genes obtained by differential analysis and weighted gene co-expression network analysis, we used three machine learning algorithms to identify 4 IUGR-related hub genes (IUGR-HGs), namely, ADAM9, CRYL1, NDP52, and SERPINA7, whose ROC curves showed that they are a good diagnostic target for IUGR. Next, we identified two molecular subtypes of IUGR through consensus clustering analysis and constructed a gene scoring system based on the IUGR-HGs. The results showed that the IUGR score was positively correlated with the risk of IUGR. The AUC value of IUGR scoring accuracy was 0.970. Finally, we constructed a new artificial neural network model based on the four IUGR-HGs to diagnose sheep IUGR, and its accuracy reached 0.956. In conclusion, the IUGR-HGs we identified provide new potential molecular markers and models for the diagnosis of IUGR in sheep; they can better diagnose whether sheep have IUGR. The present findings provide new perspectives on the diagnosis of IUGR.

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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

Cited by 5 publications

References 27 publications

Partial Thyroid Hormone-Binding Globulin Deficiency: A Case Report and Literature Review

Partial Thyroid Hormone-Binding Globulin Deficiency: A Case Report and Literature Review

Four Markers Useful for the Distinction of Intrauterine Growth Restriction in Sheep

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

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