Compound heterozygous mutations in the gamma-glutamyl carboxylase gene cause combined deficiency of all vitamin K-dependent blood coagulation factors.
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Rost S, Fregin A, Koch D, Compes M, Muller CR, Oldenburg J
Compound heterozygous mutations in the gamma-glutamyl carboxylase gene cause combined deficiency of all vitamin K-dependent blood coagulation factors.
Br J Haematol. 2004 Aug;126(4):546-9.
- PubMed ID
- 15287948 [ View in PubMed]
- Abstract
Hereditary combined deficiency of the vitamin K-dependent coagulation factors II, VII, IX, X, protein C, S and protein Z (VKCFD) is a very rare autosomal recessive inherited bleeding disorder. The phenotype may result from functional deficiency of either the gamma-glutamyl carboxylase (GGCX) or the vitamin K epoxide reductase (VKOR) complex. We report on the third case of VKCFD1 with mutations in the gamma-glutamyl carboxylase gene, which is remarkable because of compound heterozygosity. Two mutations were identified: a splice site mutation of exon 3 and a point mutation in exon 11, resulting in the replacement of arginine 485 by proline. Screening of 100 unrelated normal chromosomes by restriction fragment length polymorphism and denaturing high-performance liquid chromatography analysis excluded either mutation as a frequent polymorphism. Substitution of vitamin K could only partially normalize the levels of coagulation factors. It is suggested that the missense mutation affects either the propeptide binding site or the vitamin K binding site of GGCX.