MOLECULAR-BASES OF CRM(-X DEFICIENCY - A FREQUENT MUTATION (SER334PRO) IN THE CATALYTIC DOMAIN AND A SUBSTITUTION (GLU102LYS) IN THE 2ND EGF-LIKE DOMAIN() FACTOR)

The presence of gene lesions in coagulation factor X (FX, Stuart facto r) was investigated in asymptomatic subjects with FX deficiency charac terized by the presence of dysfunctional molecules in plasma, as demon strated by the discrepancy between clotting activity and antigen level . A missense mutation (Ser334Pro) in the catalytic domain was found in three unrelated families in both the homozygous and the heterozygous conditions, and also in the compound heterozygous form with the substi tution of Lys for 102 Glu. None of the mutations was detected in 40 un related subjects from the same geographic area. The Ser334Pro mutation affects a serine protease region characterized by extensive variation in the coagulation factors but conserved in mammalian factor X molecu les. The Glu102Lys mutation affects a residue of the second EGF-like m odule also conserved in protein C. Both mutated residues are surface-e xposed and found in protein regions suggested to be involved in macrom olecular interactions which are impaired in the dysfunctional molecule s.