Molecular bases of CRM+ factor X deficiency: a frequent mutation (Ser334Pro) in the catalytic domain and a substitution (Glu102Lys) in the second EGF-like domain.
The presence of gene lesions in coagulation factor X (FX, Stuart factor) was investigated in asymptomatic subjects with FX deficiency characterized by the presence of dysfunctional molecules in plasma, as demonstrated 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 substitution of Lys for 102 Glu. None of the mutations was detected in 40 unrelated 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 molecules. The Glu102Lys mutation affects a residue of the second EGF-like module also conserved in protein C. Both mutated residues are surface-exposed and found in protein regions suggested to be involved in macromolecular interactions which are impaired in the dysfunctional molecules.
Marchetti
G
G
Centro Studi Biochimici Patologie del Genoma Umano-Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Italy.
Castaman
G
G
Pinotti
M
M
Lunghi
B
B
Di Iasio
M G
MG
Ruggieri
M
M
Rodeghiero
F
F
Bernardi
F
F
D001483:Base Sequence; D001777:Blood Coagulation / Q000235:genetics; D015153:Blotting, Western; D005091:Exons; D005170:Factor X / Q000235:genetics*; D005171:Factor X Deficiency / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic
D005170:Factor X