Factor IX Zutphen. A genetic variant of blood coagulation factor IX with an abnormally high molecular weight

A genetic variant of blood coagulation factor IX has been isolated from the plasma of a patient with severe hemophilia B (congenital factor IX deficiency). The isolated variant--factor IX Zutphen--has a strongly reduced affinity for binding of Ca2+, it cannot be cleaved proteolytically by factor XIa, and it has a molecular weight of about 90,000, which is much higher than the 65,000 found for normal factor IX and acarboxy factor IX. Available data indicate that these unique properties of factor IX Zutphen are connected with the presence of an extra polypeptide (molecular weight 33,000) that is linked to the factor IX molecule by a disulfide bond and thus prevents effective binding of Ca2+ or factor XIa. Such a model might explain the extremely low specific coagulant activity of factor IX Zutphen.