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
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.
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.
