Somatic mosaicism and compound heterozygosity in female hemophilia B

Sequencing the complete factor IX gene of 2 sisters with hemophilia B with different phenotypes and no family history of hemorrhagic diathesis reveale d a common 5' splice site mutation in intron 3 (T6704C) in both and an addi tional missense mutation (I344T) in one. The presence of dysfunctional anti gen in the latter strongly suggested that these mutations are in trans. Nei ther mutation was found in leukocyte DNA from the asymptomatic parents, but the mother was in somatic mosaicism for the shared splice site mutation. T his case illustrates the importance of defining the phenotype and consideri ng somatic mosaicism in sporadic cases. It underlines the limitations of co mplete gene sequencing for the detection of mosaicism and has implication f or genetic counseling, (Blood. 2000;96: 1585-1587) (C) 2000 by The American Society of Hematology.