Carrier detection by direct gene analysis in a family with haemophilia B (factor IX deficiency)

DNA from a patient with severe factor IX deficiency (haemophilia B) in whom an inhibitor to factor IX had developed was studied with four genomic gene probes specific for the factor IX gene. All gave a negative result, indicating at least a partial gene deletion. Eight female relatives, covering four generations, were also studied. Restriction-enzyme-fragmented DNA was probed in each case and the level of binding assessed by darkening of the autoradiograph. The DNA of this patient's sister and mother had reduced signals, when compared with that of normal female subjects, indicating the presence of the defective gene. However, the other six female subjects (grandmother, great-grandmother, maternal aunt, and three female cousins) had normal signals. Levels of factor IX and factor IX antigen were also normal in these subjects. By direct gene analysis in this family, the point of mutation has been identified (mother) and diagnosis of the sister as a carrier confirmed.