Analysis of A Pedigree with Hereditary Coagulation Factor Ⅻ Deficiency Caused by Compound Heterozygous Mutations / 中国实验血液学杂志

OBJECTIVE@#To analysis clinical phenotype and potential genetic cause of a family affected with hereditary coagulation factor Ⅻ deficiency.@*METHODS@#The prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-Dimer (D-D), coagulation factor Ⅻ activity (FⅫ:C) and coagulation factor Ⅻ antigen (FⅫ:Ag) were determined for phenotype diagnosis of the proband and his family members(3 generations and 5 people). Targeted capture and whole exome sequencing were performed in peripheral blood sample of the proband. Possible disease-causing mutations of F12 gene were obtained and further confirmed by Sanger sequencing. The corresponding mutation sites of the family members were analyzed afterwards. The online bioinformatics software AutoPVS1 and Mutation Taster was used to predict the effects of mutation sites on protein function.@*RESULTS@#The APTT of the proband was significantly prolonged, reaching 180.9s. FⅫ:C and FⅫ:Ag of the proband was significantly reduced to 0.8% and 4.17%, respectively. The results of whole exome sequencing displayed that there were compound heterozygous mutations in F12 gene of the proband, including the c.1261G＞T heterozygous nonsense mutation in exon 11 (causing p.Glu421*) and the c.251dupG heterozygous frameshift mutation in exon 4 (causing p.Trp85Metfs*53). Both mutations are loss of function mutations with very strong pathogenicity, leading to premature termination of the protein. AutoPVS1 and Mutation Taster software predicted both mutations as pathogenic mutations. The results of Sanger sequencing revealed that c.1261G＞T heterozygous mutation of the proband was inherited from his mother, for which his brother and his daughter were c.1261G＞T heterozygous carriers. Genotype-phenotype cosegregation was observed in this family.@*CONCLUSION@#The c.1261G＞T heterozygous nonsense mutation in exon 11 and the c.251dupG heterozygous frameshift mutation in exon 4 of the F12 gene probably account for coagulation factor Ⅻ deficiency in this family. This study reports two novel pathogenic F12 mutations for the first time worldwide.

Coagulation factor XII deficiency: Clinical report of 7 patients and literature review / 中国输血杂志

【Objective】 To retrospectively analyze the clinical manifestations and laboratory characteristics of 7 patients with coagulation factor Ⅻ deficiency in our hospital from February 2016 to January 2020 in order to improve the understanding of diagnosis and treatment for the diseases. 【Methods】 The clinical data of 7 patients with coagulation factor Ⅻ deficiency were analyzed, and related literatures were reviewed. 【Results】 All the 7 patients showed significantly prolonged APTT without bleeding or thrombosis. Among them, 1 had a positive family history, and 1 acquired coagulation factor Ⅻ deficiency secondary to the tumor. 【Conclusion】 It is very necessary to comprehensively screen related internal and external coagulation factors and acquired factors in patients with prolonged APTT but no bleeding, so as to avoid missed diagnosis, misdiagnosis and over treatment.