PS1103 NOVEL COMPOUND HETEROZYGOUS MUTATIONS CAUSING FACTOR XI DEFICIENCY IN UNRELATED TWO CHINESE PATIENTS

Background: Coagulation factor XI deficiency is a rare bleeding disorder, whose molecular mechanism is not well understood. Aims: To investigate the molecular pathogenesis of coagulation factor XI (FXI) deficiency in two unrelated Chinese patients Methods: The diagnosis was validated by coagulant assays: APTT and correct test, PT and coagulation factors activities. The patients’ DNA were extracted and all exons and flanking sequences of FXI gene were amplified using PCR. After purified, the products were sequenced directly, the mutations were detected by comparing with wild sequences and analysed using some bioinformatics software. Results: The two patients were diagnosed as coagulation factor XI deficiency due to prolonged APTT, corrected APTT and low activities of coagulation factor FXI. The results of APTT, corrected APTT and FXI:C were 88.1 s, 32.9 s,1.1% and 107.1 s, 31.5 s, 3.8% for patient1 and patient2, respectively. Genetic analysis showed compound heterozygous mutations g.1251–1G>A and g.1271delT in patient1 and the sequencing results of TA plasmid clones found that the two mutations were located on different single strands of chromosomes. Double heterozygous mutations g.1070A>G and g.1446C>G were detected in patient2 resulting in Lys357Arg and Cys482Stop. Software analysis suggested the mutations probably brought amino acid sequence changed, protein features affected and splice site changed. Summary/Conclusion: Double heterozygous mutations g.1251–1G>A, g.1271delT and g.1070A>G, g.1446C>G had been identified in unrelated two coagulation factor XI deficiency Chinese patients, which might be the reasons for their prolonged APTT and low FXI:C. To the best of our knowledge, the four mutations are reported firstly in literature.