Analysis of a Chinese pedigree with Hereditary coagulation factor Ⅻ deficiency due to compound heterozygous variants of Ⅻ gene
10.3760/cma.j.cn511374-20220220-00117
- VernacularTitle:p．Cys238Leufs*73和p.Glu521Lys复合杂合变异所致遗传性凝血因子Ⅻ缺陷症一个家系的分析
- Author:
Haixiao XIE
1
;
Huanhuan WANG
1
;
Meina LIU
1
;
Huinan XIA
1
;
Yuan CHEN
1
;
Kaiqi JIA
1
;
Lihong YANG
1
;
Mingshan WANG
1
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
- Publication Type:Journal Article
- Keywords:
Coagulation factor Ⅻ deficiency;
Genetic variant;
Bioinformatic analysis;
F12 gene
- From:
Chinese Journal of Medical Genetics
2025;42(3):282-285
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze a Chinese pedigree with Hereditary coagulation factor Ⅻ (FⅫ) deficiency duo to variants of F12 gene and explore its molecular pathogenesis. Methods:A patient who underwent laparoscopic cystectomy at the Department of Gynecology of the First Affiliated Hospital of Wenzhou Medical University in June 2012 was selected as the study subject. Coagulation factor indexes of the proband and her family members (5 individuals from three generations) were determined. All exons, flanking sequences, 5′ and 3′ untranslated regions of the F12 gene of the proband and her family members were analyzed by direct sequencing. Three bioinformatics software was used to analyze the conservation, pathogenicity and protein model of the variant. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No. 2012-17). Results:The activated partial thromboplastin time (APTT), FⅫ activity (FⅫ: C) and FⅫ antigen (FⅫ: Ag) of the proband was 180.0 s, 1.0% and 2.1%, respectively. DNA sequencing revealed that she has harbored compound heterozygous variants of the F12 gene, namely c. 712_713insT (p.Cys238Leufs *73) in exon 8 and c. 1561G>A (p.Glu521Lys) in exon 13. Her mother and younger son were heterozygous for the p. Cys238Leufs*73 variant, while her older son was heterozygous for the p. Glu521Lys variant. Bioinformatic analysis suggested that Cys238 is highly conserved and p. Cys238Leufs*73 is a pathogenic variant, which eventually resulted in a truncated protein. Conclusion:The c. 712_713insT and c. 1561G>A compound heterozygous variants of the F12 gene probably underlay the decreased FⅫ level in this pedigree, among which c. 712_713insT (NM_000505) was unreported previously.
