Recombinant expression of wildtype and mutated γ-glutamyl carboxylase

So far, only 10 different mutations have been identified in the GGCX gene of VKCFD patients. Four of them (Trp157Arg, Leu394Arg, Trp501Ser, Thr591Lys) could be proven to be causative for the VKCFD1 phenotype by recombinant expression of the mutated GGCX in insect cells and subsequent measurement of GGCX activity. As GGCX does not only modify coagulation proteins but also the bone metabolites osteocalcin and matrix gla protein, mutations in the GGCX gene can lead to growth retardation and facial dysmorphy, too. One patient carrying two of the four characterized mutations showed this phenotype in addition to the bleeding disorder. This shows that the phenotype of VKCFD1 can vary dependent on the causative mutations.