Molecular mechanism analysis of a family with hereditary coagulation F Ⅺ deficiency caused by compound heterozygous mutations
10.3760/cma.j.cn121090-20230814-00065
- VernacularTitle:1例复合杂合突变导致遗传性凝血因子Ⅺ缺陷症的分子致病机制
- Author:
Yuan CHEN
1
;
Langyi QIN
;
Shuangnyu LIN
;
Lihong YANG
;
Ke ZHANG
;
Longying YE
;
Yanhui JIN
;
Mingshan WANG
Author Information
1. 温州医科大学附属第一医院医学检验中心，浙江省检验诊断及转化研究重点实验室，温州 325015
- From:
Chinese Journal of Hematology
2024;45(3):294-298
- CountryChina
- Language:Chinese
-
Abstract:
A 34 year old female patient was scheduled to undergo surgical resection due to a "breast nodule". Preoperative examination revealed an activated partial thromboplastin time (APTT) of 66.2 seconds, coagulation factor Ⅺ activity (FⅪ: C) of 2%, and FⅪ antigen (FⅪ: Ag) of 40.3%. The patient and family members showed no abnormal bleeding symptoms. Diagnosed as hereditary coagulation factor Ⅺ deficiency. Genetic testing revealed that the F11 gene had a heterozygous nonsense mutation in exon 10, c.1107C>A (p.Tyr351stop), and a heterozygous missense mutation in exon 13, c.1562A>G (p.Tyr503Cys). The father and son were p Heterozygous carriers of Tyr351stop mutation, while the mother and daughter are p Heterozygous carriers of Tyr503Cys mutations. The in vitro expression results showed that p The Tyr351stop mutation resulted in a significant decrease in the transcription level of F11 gene, while p The Tyr503Cys mutation has no effect on the transcription level and protein expression level of F11 gene, but it leads to a significant decrease in the level of FⅪ:C in the cell culture supernatant.
