Combined haemophilia A and B in a pedigree with mosaicism of the F9 gene mutation in HB index's maternal grandfather
Abstract number: PP-TH-564
Lu1 Y., Wang1 X., Ding1 Q., Dai1 J., Xi2 X., Xie3 B., Wang4 M., Wang5 H.
11Clinical Transfusion Department 22State Key Laboratory of Medcine Genomics, Ruijin Hospital affiliated to Medical College of JiaoTong University, Shanghai 33Laboratory department, Wenzhou third people's hospital 44Laboratory department, Wenzhou first people's hospital, Wenzhou 55Shanghai Institute of hematology, Ruijin Hospital affiliated to Medical College of JiaoTong University, Shanghai, China
How-to-cite Lu Y, Wang X, Ding Q, Dai J, Xi X, Xie B, Wang M, Wang H. Combined haemophilia A and B in a pedigree with mosaicism of the F9 gene mutation in HB index's maternal grandfather. Journal of Thrombosis and Haemostasis 2009; Volume 7, Supplement 2: Abstract PP-TH-564
Background: Haemophilia A and B are x-linked inherited bleeding disorders due to the deficiency of coagulation factor VIII and IX. We report an extremely rare family with combined factor VIII and IX deficiencies.
Objective: To make genetic diagnosis of this family and carrier detection of the Haemophilia B patient's maternal aunt.
Methods: The APPT, PT, TT, Fg, FVIII:C and FIX:C were detected to make phenotypic diagnosis. LD-PCR and PCR were adopted for the screening of INV22 and INV1 respectively. F9 gene was directly sequenced. Six STR sites related to F9 gene were combined together to apply to the linkage analysis. Primer extension PCR was used to analyze the mosaicism.
Results: Family studies showed that the indexed patient was a severe HA, while his son was a moderate HB patient. INV22 was identified in the HA proband and p. Ser365Cys in F9 gene was found in the HB boy. The causative mutation in F9 gene originated from the HB boy's maternal grandfather by linkage analysis. F9 gene sequencing results showed that the mother of HB patient was a mutation carrier and the maternal grandfather had the wild-type F9 gene in his peripheral blood leukocytes. While, 14.4% somatic mosaicism of the causative mutation was revealed in the oral cells of the grandfather. No mutation was found in the boy's maternal aunt.
Conclusion: Combined deficiency of coagulation factor VIII and IX in this family due to association of two distinct genetic defects. HA due to INV22, while HB resulted from F9 gene mutation due to mosaicism of this mutation in maternal grandfather. The boy's maternal aunt was diagnosed as a normal female.
Disclosure of interest: none declared.