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.
Adult ; Female ; Humans ; Male ; Middle Aged ; China/ethnology* ; Factor XI/chemistry* ; Factor XI Deficiency/genetics* ; Homozygote ; Pedigree ; Retrospective Studies ; East Asian People/genetics*