Open AccessCompound hemizygous variants in SERPINA7 gene cause thyroxine‐binding globulin deficiency
Author(s) -
Fang Yanlan,
Chen Hong,
Chen Qingqing,
Wang Chunlin,
Liang Li
Publication year - 2021
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1571
Subject(s) - thyroxine binding globulin , gene , globulin , medicine , endocrinology , biology , genetics , thyroid , triiodothyronine
Sub‐heading Compound hemizygous variants in SERPINA7 gene. Background Thyroxine‐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 Methods In 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. Conclusion Analyses 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.