This variant has been called factor IX Hilo and factor IX Novara.
A subset of hemophilia B patients have a prolonged prothrombin time (PT) when exposed to bovine (or ox) brain tissue; these CRM+ patients are classified as having hemophilia B(M) (see 306900). Huang et al. (1989) demonstrated a point mutation in a hemophilia B(M) variant, factor IX Hilo. Glutamine (CAG) was substituted for arginine (CGG) at amino acid 180 in exon 6 (G-to-A at nucleotide 20519). Bertina et al. (1990) found the same mutation. The hemophilia was clinically severe.
Lefkowitz et al. (1993) noted that the bovine brain tissue in studies of hemophilia B(M) is the source of thromboplastin, or tissue factor (F3; 134390); PT times determined with thromboplastin from rabbit brain or human brain are not reported to be prolonged. However, in various studies of factor IX Hilo, Lefkowitz et al. (1993) found that either normal F9 or Hilo F9 prolonged the PT regardless of the tissue factor source, but the prolongation required high concentrations of factor IX when rabbit or human brain was used. With bovine thromboplastin, factor IX Hilo was significantly better than normal factor IX at prolonging the PT. In addition, the prolongation times depended on the amounts of factors IX and X used in the assays.
