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| Phenotype and gene mutation analysis of a family with hereditary antithrombin deficiency |
| ZHOU Xingxing, XIE Yaosheng, XIE Haixiao, WANG Mingshan. |
| Center of Laboratory Medicine, the First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou 325015, China |
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| Cite this article: |
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ZHOU Xingxing,XIE Yaosheng,XIE Haixiao, et al. Phenotype and gene mutation analysis of a family with hereditary antithrombin deficiency[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2022, 52(12): 993-998.
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Abstract Objective: To analyze the coagulation index and genotype of a patient with hereditary antithrombin (AT) deficiency and his family members, and to explore its molecular pathogenesis. Methods:The blood coagulation indexes such as plasma AT activity (AT:A) and AT antigen (AT:Ag) in the peripheral blood of each family member were detected on Stago instrument; the peripheral blood DNA was extracted and sequenced, and the gene mutation sites were located. The effect of mutations on protein function was analyzed by bioinformatics software. Results: The AT:A of the proband and his maternal grandmother, father, mother and younger brother all decreased to varying degrees, and AT:Ag decreased synchronously. There were no obvious abnormalities in PC:A and PS:A in all family members, showing type I AT Defects. Genetic analysis showed that the proband had a heterozygous missense mutation of c.1A>G (p.Tyr2stop) in exon 1 of SERPINC1 gene and a heterozygous synonymous mutation of c.1005G>A in exon 5; his father carried c.1A>G heterozygous missense mutation, his grandmother, mother and younger brother carry c.1005G>A heterozygous synonymous mutation.Conservation analysis showed that Tyr2 was highly conserved among homologous species. Analysis made by three online bioinformatics software, i.e., MutationTaster, PolyPhen-2 and LRT, showed that p.Tyr2stop mutation was “pathogenic and harmful”; protein model analysis showed that the p.Tyr2stop mutation could cause premature termination of AT gene translation, resulting in a truncated protein. Conclusion: The AT:A and AT:Ag reduction to different degrees in the proband and family members was related to the c.1A>G heterozygous missense mutation and the c.1005G>A heterosynonymous mutation in the SERPINC1 gene.
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Received: 20 September 2022
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YU Xiaomin,CHANG Guolin, ZHENG Yiyang, CHEN Cheng, TANG Shiyi, WU Xinyuan, LYU Jia, LIN Xiangyang, ZHU Liqing.. The pathogenic mechanism of inherited protein C deficiency caused by Ala333Thr mutation[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2022, 52(5): 352-357. |
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