Double Heterozygous Mutations (Cys247Tyr and 252delAsn) Cause Factor XII Deficiency in a Chinese Family

Abstract

AbstractObjective To study the molecular basis of human coagulation factor XII (FXII) deficiency in a Chinese family.Methods Routine blood coagulation indexes were detected by a one-stage clotting method, whereas FXII antigen was detected by enzyme linked immunosorbent assay. DNA sequencing was applied to find mutations in the F12 gene. Bioinformatics and conservative analyses were performed to analyze possible effects of the mutation.Results The proband had significantly prolonged activated partial thromboplastin time (141.9 seconds), and her FXII clotting activity was decreased to 5%. Genetic analysis revealed that the propositus carried a heterozygous missense mutation c.797G > A in exon 8 resulting in Cys247Tyr and deletion mutation c.809_811delACA in exon 9 resulting in 252delAsn. Bioinformatics results indicated that the mutation had affected the function of the protein.Conclusion The c.797G > A heterozygous missense variation and the c.809_811delACA heterozygous deletion variation are associated with decreased FXII levels in this family, of which c.797G > A is first reported in the world.