title: Novel mutation in the gamma-glutamyl carboxylase gene resulting in congenital combined deficiency of all vitamin K-dependent blood coagulation factors.
abstract: A mutation in the gamma-glutamyl carboxylase gene leading to a combined congenital deficiency of all vitamin K-dependent coagulation factors was identified in a Lebanese boy. He is the first offspring of consanguineous parents and was homozygous for a unique point mutation in exon 11, resulting in the conversion of a tryptophan codon (TGG) to a serine codon (TCG) at amino acid residue 501. Oral vitamin K(1) administration resulted in resolution of the clinical symptoms. Screening of several family members on this mutation with an RFLP technique revealed 10 asymptomatic members who were heterozygous for the mutation, confirming the autosomal recessive pattern of inheritance of this disease. In 50 nonrelated normal subjects, the mutation was not found. This is the second time a missense mutation in the gamma-glutamyl carboxylase gene is described that has serious impact on normal hemostasis.
authors.affiliation: Department of Pediatrics, Sainte-Therese Hospital, Beirut, Lebanon.
authors.forename: H M
authors.initials: HM
authors.lastname: Spronk
authors.forename: R A
authors.initials: RA
authors.lastname: Farah
authors.forename: G R
authors.initials: GR
authors.lastname: Buchanan
authors.forename: C
authors.initials: C
authors.lastname: Vermeer
authors.forename: B A
authors.initials: BA
authors.lastname: Soute
mesh_terms: D001779:Blood Coagulation Factors / Q000187:drug effects*; D019735:Carbon-Carbon Ligases / Q000235:genetics*; D004252:DNA Mutational Analysis; D006470:Hemorrhage / Q000209:etiology; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D015675:Osteocalcin / Q000097:blood; D010375:Pedigree; D017354:Point Mutation; D014812:Vitamin K / Q000008:administration & dosage / Q000494:pharmacology; D014813:Vitamin K Deficiency / Q000150:complications* / Q000201:enzymology* / Q000209:etiology
chemical_list: D001779:Blood Coagulation Factors; D015675:Osteocalcin; D014812:Vitamin K; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase