Molecular defects in CRM+ factor VII deficiencies: modelling of missense mutations in the catalytic domain of FVII

摘要: Summary. The molecular defects causing CRM+ factor VII deficiency were investigated in seven unrelated subjects and several members of their families. Four missense mutations located the catalytic domain found. previously reported 304ArgGln substitution was present homozygous heterozygous forms, with different polymorphic haplotypes, thus demonstrating that it is recurrent frequent Italian population. 310Cys Phe found form compound condition nonsense mutation 356Trpstop. Two mutations, 298MetIle 342GlyArg, respectively. Molecular heterogeneity further increased by finding 353ArgGln polymorphism doubly 304 342 mutations. Plausible explanations for loss FVII function inspecting a model serine protease VIIa. Inefficient activation site predicted 298MetIle. 342GlyArg would directly distort geometry ‘oxyanion hole’preventing formation substrate enzyme intermediate. 310Cyshe to have an adverse effect on tissue interaction. These point important regions molecule.