Genetic analysis of a pedigree with hereditary coagulation factor Ⅺ deficiency caused by a homozygous p. Thr299Ser variant of F11 gene
10.3760/cma.j.cn511374-20241108-00581
- VernacularTitle:p．Thr299Ser基因纯合变异致遗传性凝血因子Ⅺ缺陷症一个家系的遗传学分析
- Author:
Conglian WU
1
;
Yiyin CHEN
1
;
Yancheng JIANG
1
;
Zixuan CHEN
1
;
Mengcha TIAN
1
;
Zhishan ZHANG
1
Author Information
1. 福建医科大学附属泉州第一医院检验科，泉州 362000
- Publication Type:Journal Article
- Keywords:
Hereditary coagulation factor Ⅺ deficiency;
F11 gene;
Homozygote;
Missense variant
- From:
Chinese Journal of Medical Genetics
2025;42(8):905-910
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the phenotypic and genotypic characteristics of a Chinese pedigree affected with Hereditary coagulation factor Ⅺ (FⅪ) deficiency.Methods:A female patient with FⅪ deficiency and her family members (five individuals from three generations) who presented at Quanzhou First Hospital Affiliated to Fujian Medical University on September 19, 2024 due to diarrhea and fever were selected as study subjects. A retrospective study was conducted to collect the patients′ clinical data. Peripheral venous blood samples were collected from the patient and her family members. Genomic DNA was extracted, followed by sequencing of all exons and flanking sequences of the F11 gene. Candidate variants were validated by Sanger sequencing of the family members, and their pathogenicity was classified according to the guidelines of the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Quanzhou First Hospital [Approval No.: Quanyi Lun (2024) K281]. Results:The patient exhibited significantly prolonged activated partial thromboplastin time (APTT) of 80.9 seconds, while FⅪ activity (FⅪ: C) and FⅪ antigen (FⅪ: Ag) levels were extremely low (2% and 3%, respectively). Genetic analysis revealed that the proband harbored homozygous c. 896C>G (p.Thr299Ser) missense variant in exon 9 of the F11 gene, for which her son was heterozygous. The variant was located in a highly conserved domain. Although Mutation Taster predicted it as a polymorphism, SIFT, PolyPhen-2, and LRT analyses suggested it to be likely pathogenic. Protein modeling indicated that the p. Thr299Ser variant may alter the hydrogen bonds between amino acids, thereby affecting the structure and function of the FⅪ protein. According to the ACMG guidelines, c. 896C>G was rated as a likely pathogenic variant (PM1+ PM2_Supporting+ PP1_Strong+ PP3+ PP4). Conclusion:The c. 896C>G (p.Thr299Ser) missense variant of the F11 gene probably underlay the FⅪ deficiency in this pedigree. Above finding has enriched the mutational spectrum of the F11 gene and provided a basis for genetic counseling and prenatal diagnosis for this family.
