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Molecular Diagnosis of Haemophilia B Leyden In a Chinese Pedigree: C>G Transition At Position +9 of the FIX Gene

Abstract 4651 Objective To investigate the molecular change causing Haemophilia B in a Chinese family. Methods The peripheral blood samples had been extracted from proband and his family members. The activated partial thromboplastin time (APTT), prothrombin time (PT) and FIX activity (FIX:C) were adopted for phenotype diagnosis. All the 8 exons and their flank boundaries were amplified by polymerase chain reaction (PCR). The PCR products were sequenced directly. The corresponding DNA fragments of their famliy members were amplified by PCR and then screeded by direct sequencing. Results The 3-year-old Chinese boy had persistent nose swelling for 10 days from an injury. He had a long APTT of 96.6s which could be corrected to 30.2s with mixed normal plasma. PT, TT and fibrogen level was in normal range, respectively. FVIII:C was 54%, FIX:C was 1.6% and AT:C was 115%. DNA sequencing of the proband’s F9 gene revealed that there was a C>G mutation at nt +9 in the promoter region. His mother, maternal grandmother and two maternal grandmother’s sisters all had the same C/G genotype, with FIX:C 44%, 89%, 81% and 67%, respectively. His maternal uncle, aged 30, had the C>G mutation with FIX:C 40% and another maternal uncle, aged 12, had the same mutation with FIX:C 4.2%. To date, there are only two cases with Haemophilia B Leyden reported from Asia, one from Thailand (nt +8 T>C) and the other from HongKong (nt +6 T>A). The mutation at nt +9 C>G lies in the binding sites for transactivating factors, such as CCAAT/enhancer binding protein (C/EBP), affects the first (site 1: nt +1 to +18) of five known cisacting sites in the FIX promoter. The clinical picture of the proband reported herein and his maternal uncle with the same genetic defect conforms to the Leyden phenotype, because the uncle now has a relatively normal FIX level (40%) and no recent bleeding episodes. Conclusion The mutation at nt +9 C>G in FIX promoter might be the causative one leading to FIX deficiency in this Chinese pedigree.To the best of our knowledge, this is the first time to report the mutation at this site of FIX promoter. Disclosures: No relevant conflicts of interest to declare.