Haiyue Zhang1, Siqi Liu1, Shasha Luo1, Yanhui Jin1, Lihong Yang1, Haixiao Xie1, Jingye Pan1, Mingshan Wang2. 1. Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 2. Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China, wywms@126.com.
Abstract
OBJECTIVE: To study the molecular basis of hereditary antithrombin (AT) deficiency in a Chinese family. It will help us understand the pathogenesis of this type of disease. METHOD: AT activity (AT:A) and the AT antigen (AT:Ag) level were tested by chromogenic substrate and immunoturbidimetry, respectively. To identify the novel mutations, SERPINC1 gene sequencing was carried out. The possible impact of the mutations was analyzed by model and bioinformatic analyses. RESULTS: AT:A and the AT:Ag level of the proband were 43% and 113 mg/L (normal range: 98-119% and 250-360 mg/L), respectively. Sequencing analysis revealed compound heterozygous mutations, including a frameshift mutation (c.318_319insT) resulting in Asn75stop and a missense mutation (c.922G>T) resulting in Gly276Cys. The bioinformatic and model analyses indicated that these mutations may disrupt the function and structure of the AT protein. CONCLUSION: We detected 2 novel heterozygous mutations (c.318_319insT and c.922G>T) in the proband, and these were associated with decreased AT:A.
OBJECTIVE: To study the molecular basis of hereditary antithrombin (AT) deficiency in a Chinese family. It will help us understand the pathogenesis of this type of disease. METHOD: AT activity (AT:A) and the AT antigen (AT:Ag) level were tested by chromogenic substrate and immunoturbidimetry, respectively. To identify the novel mutations, SERPINC1 gene sequencing was carried out. The possible impact of the mutations was analyzed by model and bioinformatic analyses. RESULTS: AT:A and the AT:Ag level of the proband were 43% and 113 mg/L (normal range: 98-119% and 250-360 mg/L), respectively. Sequencing analysis revealed compound heterozygous mutations, including a frameshift mutation (c.318_319insT) resulting in Asn75stop and a missense mutation (c.922G>T) resulting in Gly276Cys. The bioinformatic and model analyses indicated that these mutations may disrupt the function and structure of the AT protein. CONCLUSION: We detected 2 novel heterozygous mutations (c.318_319insT and c.922G>T) in the proband, and these were associated with decreased AT:A.