Premium
Molecular bases of CRM + factor X deficiency: a frequent mutation (Ser334Pro) in the catalytic domain and a substitution (Glul02Lys) in the second EGF‐like domain
Author(s) -
MARCHETTI G.,
CASTAMAN G.,
PINOTTI M.,
LUNGHI B.,
IASIO M. G.,
RUGGIERI M.,
RODEGHIERO F.,
BERNARDI F.
Publication year - 1995
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1995.tb05214.x
Subject(s) - substitution (logic) , domain (mathematical analysis) , mutation , amino acid substitution , chemistry , genetics , biology , computer science , gene , mathematics , mathematical analysis , programming language
Summary. 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 Glul02Lys 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.