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Compound heterozygous mutations in the gamma-glutamyl carboxylase gene cause combined deficiency of all vitamin K-dependent blood coagulation factors.
Br J Haematol 2004; 126(4):546-9BJ

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.

Authors+Show Affiliations

Institute of Human Genetics, University Würzburg, Würzburg, Germany.

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15287948

Citation

Rost, Simone, et al. "Compound Heterozygous Mutations in the Gamma-glutamyl Carboxylase Gene Cause Combined Deficiency of All Vitamin K-dependent Blood Coagulation Factors." British Journal of Haematology, vol. 126, no. 4, 2004, pp. 546-9.
Rost S, Fregin A, Koch D, et al. Compound heterozygous mutations in the gamma-glutamyl carboxylase gene cause combined deficiency of all vitamin K-dependent blood coagulation factors. Br J Haematol. 2004;126(4):546-9.
Rost, S., Fregin, A., Koch, D., Compes, M., Müller, C. R., & Oldenburg, J. (2004). Compound heterozygous mutations in the gamma-glutamyl carboxylase gene cause combined deficiency of all vitamin K-dependent blood coagulation factors. British Journal of Haematology, 126(4), pp. 546-9.
Rost S, et al. Compound Heterozygous Mutations in the Gamma-glutamyl Carboxylase Gene Cause Combined Deficiency of All Vitamin K-dependent Blood Coagulation Factors. Br J Haematol. 2004;126(4):546-9. PubMed PMID: 15287948.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Compound heterozygous mutations in the gamma-glutamyl carboxylase gene cause combined deficiency of all vitamin K-dependent blood coagulation factors. AU - Rost,Simone, AU - Fregin,Andreas, AU - Koch,Dieter, AU - Compes,Markus, AU - Müller,Clemens R, AU - Oldenburg,Johannes, PY - 2004/8/4/pubmed PY - 2004/9/21/medline PY - 2004/8/4/entrez SP - 546 EP - 9 JF - British journal of haematology JO - Br. J. Haematol. VL - 126 IS - 4 N2 - 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. SN - 0007-1048 UR - https://www.unboundmedicine.com/medline/citation/15287948/Compound_heterozygous_mutations_in_the_gamma_glutamyl_carboxylase_gene_cause_combined_deficiency_of_all_vitamin_K_dependent_blood_coagulation_factors_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0007-1048&date=2004&volume=126&issue=4&spage=546 DB - PRIME DP - Unbound Medicine ER -