Genetic variants of hemophilia B: detection by means of a specific PTC inhibitor.

Hemophilia B can be divided into at least two mutant forms different from the mild, moderate, and severe categories previously described. In about 90% of hemophilia B patients, PTC-inhibitor-neutralizing activity is reduced in proportion to PTC clotting activity. In about 10% of the patients, PTC-inhibitor-neutralizing activity is fully effective, whereas PTC clotting activity is reduced. Extensive pedigree studies indicate that the presence or absence of inhibitor-neutralizing activity is genetically determined. It is suggested that those hemophilia B mutants with decreased inhibitor-neutralizing material produce decreased amounts of PTC-protein. It is further suggested that those with normal levels of inhibitor-neutralizing material produce normal amounts of PTC-protein, which is structurally altered so as to lose procoagulant activity but which retains inhibitor-neutralizing activity. The latter group may be analogous to CRM(+) mutants described in bacteria and Neurospora.