Partial thyroxine-binding globulin deficiency in a family with coding region mutations in the TBG gene
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ORIGINAL ARTICLE
Partial thyroxine‑binding globulin deficiency in a family with coding region mutations in the TBG gene L.‑D. Chen1 · H.‑J. Lu2 · Y.‑L. Gan1 · S.‑W. Pang3 · Q. Zheng2 · D.‑M. Ye2 · X.‑Y. Huang1 · H.‑N. Qi2 · W.‑B. Xu2 · X.‑Z. Wen2 · L.‑H. Li1 · L. Li2 Received: 1 March 2020 / Accepted: 30 March 2020 © Italian Society of Endocrinology (SIE) 2020
Abstract Purpose T4-binding globulin (TBG) is the main thyroid hormone (TH) transporter present in human serum. Inherited thyroxine-binding globulin (TBG) deficiency is caused by mutations in the TBG (SERPINA7) gene, which is located on the X chromosome. This study was performed to report and evaluate coding region mutations in TBG gene for partial thyroxinebinding globulin deficiency. Methods A pedigree spanning four generations is described in this study. The proband is a female with partial TBG deficiency. All members of this pedigree underwent thyroid function tests, while Sanger sequencing was used to identify the TBG gene mutations. Bioinformatics databases were used to evaluate the deleterious effects of the mutation(s). Two hundred and seven unrelated individuals were used to evaluate the thyroid function of individuals with different TBG mutations. A one-way ANOVA was used to analyze the impact of the TBG mutations on thyroid function. Results TBG gene sequencing results revealed that the proband had a novel mutation in codon 27 leading to alanine to valine substitution (p.A27V). This mutation was associated with lower serum T4 levels (p T)
Hemizygote (T)
Heterozygote (C/T)
Wildtype (C)
Wildtype (C/C)
Wildtype (C/C)
Wildtype (C)
Wildtype (C/C)
Exon3 (rs1804495G > T)
Hemizygote (T)
Heterozygote (T/G)
Hemizygote (T)
Heterozygote (T/G)
Homozygote (T/T)
Wildtype (G)
Wildtype (G/G)
Mean ± SD
42.00 ± 24.12
52.00 ± 39.97
49.23 ± 11.20
47.59 ± 10.84
48.56 ± 11.50
47.76 ± 12.51
46.11 ± 10.50
p value
0.86
Mean ± SD
1.20 ± 0.22
1.40 ± 0.21
1.40 ± 0.18
1.42 ± 0.25
1.33 ± 0.15
1.69 ± 0.30
1.81 ± 1.75
p value
0.14
Mean ± SD
34.28 ± 6.14
53.38 ± 9.45
78.01 ± 8.88
89.90 ± 19.01
86.89 ± 10.75
99.01 ± 15.16
95.56 ± 20.56
p value
8.30 × 10–18
Mean ± SD
4.68 ± 0.96
4.63 ± 0.59
4.70 ± 0.40
4.33 ± 0.58
4.29 ± 0.33
4.90 ± 0.60
6.44 ± 14.39
p value
0.82
Mean ± SD
17.75 ± 3.00
14.56 ± 1.54
15.71 ± 2.08
14.61 ± 2.80
15.53 ± 2.27
15.62 ± 2.86
14.67 ± 3.09
p value
0.11
Mean ± SD
2.69 ± 1.50
3.37 ± 1.77
2.26 ± 1.02
5.19 ± 14.77
2.89 ± 1.02
3.59 ± 10.38
2.32 ± 1.92
p value
0.81
Mean ± SD
10.30 ± 2.57
13.81 ± 5.79
10.97 ± 3.99
15.48 ± 5.57
12.91 ± 3.18
16.67 ± 5.91
17.40 ± 5.34
p value
3.30 × 10–6
Genotype
Age (years) T3 (nmol/L) T4 (nmol/L) FT3 (pmol/L) FT4 (pmol/L) TSH (mU/L) TBG (μg/mL)
Group 1: p.A27V and p.L283F hemizygotes; Group 2, p.A27V and p.L283F heterozygotes; Group 3, p.L283F hemizygotes; Group 4, p.L283F heterozygotes; Group 5, p.L283F homozygotes; Group 6, wildtype males; Group 7, wildtype females
13
Journal of Endocrinological Investigation
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