Genetic variants of haemophilia B detected by immunoradiometric assay: implications for prenatal diagnosis.

Fifty patients with haemophilia B, belonging to 29 kindreds, were investigated with a highly sensitive immunoradiometric assay based on a homologous antibody to factor IX. The assay measures factor IX antigen (f.IX:Ag) in plasma down to 0.025 U/dl. Seventeen of 18 investigated patients with severe haemophilia B had very little or no f.IX:Ag. Also four of nine patients with moderately severe disease had very low antigen levels, approximately equal to their factor IX clotting activity (f.IX:C), whereas the other 5 had antigen in excess of activity. Of the 23 investigated patients with mild haemophilia B, 20 had f.IX:Ag approximately equal to f.IX:C, whereas 3 had normal amounts of antigen. One family with mild disease was found to have a possible variant of haemophilia B Leyden, earlier described in a few families with moderately severe disease. No haemophilia BM variants, characterized by prolonged prothrombin time with bovine brain thromboplastin, were found. We have shown earlier that the immunoradiometric assay of f.IX was useful in the prenatal evaluation of one fetus at risk for haemophilia B. The present study shows that the assay can be applied for prenatal diagnostic purposes in the vast majority of carriers of severe haemophilia B and in about half of the carriers of moderately severe disease.