Analysis of lower gastrointestinal bleeding caused by FXI gene mutation
WANG Huanhuan, LIU Meina,XIE Haixiao, JIA Kaiqi, ZENG Manlin, WANG Mingshan
Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China
WANG Huanhuan,LIU Meina,XIE Haixiao, et al. Analysis of lower gastrointestinal bleeding caused by FXI gene mutation[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2022, 52(4): 288-293.
Abstract：Objective: To analyze the pathogenesis of abnormal lower gastrointestinal bleeding after endoscopic rectal polypectomy in a patient with hereditary coagulation factor XI (FXI) deficiency, and to explore the relationship between the FXI mutation and lower gastrointestinal bleeding after treatment. Methods: Pedigree investigation (5 people of 3 generations in total) was made and relevant coagulation factor indexes of the patient and her family members were detected. Genomic DNA of peripheral blood was extracted for PCR amplification.All the exons, flanking sequences, 5’ and 3’ untranslated regions of FXI gene of the patient were analyzed by direct sequencing. And the corresponding mutation site was subjected to sequencing in other family members.The PyMol software was used to construct protein model before and after gene mutation. Results: The patient was admitted to hospital for abnormal lower gastrointestinal bleeding after endoscopic rectal polypectomy. The activated partial thromb oplastin time (APTT), FXI activity (FXI:C) and FXI antigen (FXI:Ag) of the patient was 50.9 s, 53% and 47.2%, respectively; The above three indicators for her father were 45.4 s, 44% and 43.1%,respectively. Gene sequencing revealed that the patient and her father had a heterozygous nonsense mutation c.841C>T (p.Gln281*) in exon 8 of the FXI gene. Protein model analysis demonstrated that the p.Gln281*mutation producing truncated protein. Conclusion: A heterozygous nonsense mutation c.841C>T (NM_000128) in exon 8 of the FXI gene is responsible for the low FXI level in this pedigree, which might be the main reason for abnormal lower gastrointestinal bleeding after endoscopic rectal polypectomy in this patient.
