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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 Aug; 126(4):546-9.BJ

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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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), 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 -