Two cases of coagulation factor Ⅺ deficiency caused by compound heterozygous mutations
10.3760/cma.j.cn511374-20201112-00793
- VernacularTitle:复合杂合变异引起的凝血因子Ⅺ缺乏症两例
- Author:
Qian LI
1
;
Min ZHOU
;
Yong XU
;
Hui ZENG
;
Yueyi XU
;
Peipei XU
;
Bing CHEN
;
Rongfu ZHOU
Author Information
1. 南京大学医学院附属鼓楼医院，南京 210008
- Keywords:
Coagulation factor Ⅺ deficiency;
Gene mutation;
Molecular mechanism
- From:
Chinese Journal of Medical Genetics
2022;39(6):597-601
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the molecular pathogenesis of two coagulation factor Ⅺ (FⅪ) deficiency patients.Methods:Coagulant assays: activated partial thromboplastin time(APTT), normal pooled-plasma corrected APTT test, PT, PT-INR and one-stage assay of coagulation factors activities were validated to diagnose coagulation factor Ⅺ deficiency. The patients’ DNA samples were extracted and all exons and flanking sequences of F11 gene were amplified using PCR. After purified, the products of PCR were sequenced directly, the mutations were detected by comparing with wild sequences and analyzed using some bio-informatics softwares. Results:The two patients were diagnosed with coagulation factor Ⅺ deficiency due to prolonged APTT, corrected APTT and low activities of coagulation factor FⅪ. The results of APTT, FⅪ∶C were 88.1s, 1.1% and 107.1s, 3.8% , and the prolonged APTT could be corrected to normal range 32.9s and 31.5s, respectively. Through genetic analysis, we discovered compound heterozygous mutations g. 1305-1G>A and g. 1325delT in patient 1 and the sequencing results of TA plasmid clones showed that the two mutations were located on different strands of chromosomes. Compound heterozygous mutations g. 1124A>G and g. 1550C>G were detected in patient 2 resulting in Lys357Arg and Cys482Trp. Software analysis indicated the mutations probably brought amino acid sequence changed, protein features affected and splice site changed.Conclusion:Compound heterozygous mutations g. 1305-1G>A, g. 1325delT and g. 1124A>G, g. 1550C>G had been identified in two coagulation factor Ⅺ deficiency patients which might be responsible for their prolonged APTT and low FⅪ∶C. To the best of our knowledge, g. 1325delT and g. 1550C>G have been reported, while g. 1124A>G and g. 1305-1G>A are reported for the first time in the literature.
