Analysis of three Chinese pedigrees affected with Hereditary factor Ⅶ deficiency due to compound heterozygous variants of F7 gene
10.3760/cma.j.cn511374-20230221-00089
- VernacularTitle:复合杂合变异所致遗传性凝血因子Ⅶ缺陷症三个家系的遗传学分析
- Author:
Longying YE
1
;
Huilin CHEN
;
Zhengxian SU
;
Ke ZHANG
;
Lihong YANG
;
Yanhui JIN
;
Mengzhen WEN
;
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
- Keywords:
Coagulation factor Ⅶ deficiency;
Genetic variant;
F7 gene;
Bioinformatics
- From:
Chinese Journal of Medical Genetics
2024;41(4):393-398
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the types of genetic variants and clinical characteristics of three Chinese pedigrees affected with Hereditary coagulation factor Ⅶ (FⅦ) deficiency.Methods:Three pedigrees who had visited the First Affiliated Hospital of Wenzhou Medical University between December 2021 and October 2022 were selected as the study subjects. Prothrombin time (PT), activated partial thromboplastin time (APTT) and FⅦ activity (FⅦ: C) were measured in the three probands and their pedigree members. All exons and their flanking sequences were analyzed by direct sequencing, and candidate variants were verified by reverse sequencing. The corresponding variant loci in the family members were also analyzed. ClustalX-2.1-win was used to analyze the conservation of the variant loci. Varcards and Spcards online software was used to predict the pathogenicity of the variants. Pymol software was used to analyze the changes in protein structure and molecular forces.Results:Three cases of hereditary FⅦ deficiency were found to have decreased FⅦ: C, prolonged PT and normal APTT. Genetic analysis identified a total of four genetic variants, and all three probands had harbored compound heterozygous variants of the F7 gene, including p. Cys389Gly and p. His408Gln in proband 1, p. Cys389Gly and IVS6+ 1G>T in proband 2, and IVS6+ 1G>T and IVS1a+ 5G>A in proband 3. Conservation analysis showed that both the p. Cys389 and p. His408 loci are highly conserved among orthologous species. Analysis with Varcards and Spcards software showed that these variants were pathogenic. Protein modeling analysis showed that the p. Cys389Gly and p. His408Gln variants may result in altered protein structures and changes in hydrogen bonds. Conclusion:The clinical manifestations of the three FⅦ-deficient probands may be attributed to the compound heterozygous variants of p. Cys389Gly/p.His408Gln, p. Cys389Gly/ⅠⅤS6+ 1G>T and ⅠⅤS6+ 1G>T/ⅠⅤS1a+ 5G>A of the F7 gene. The combination of the three compound heterozygous variants was unreported previously.
