Novel mutation in the gamma-glutamyl carboxylase gene resulting in congenital combined deficiency of all vitamin K-dependent blood coagulation factors

A mutation in the gamma -glutamyl carboxylase gene leading to a combined co ngenital deficiency of all vitamin K-dependent coagulation factors was iden tified in a Lebanese boy. He is the first offspring of consanguineous paren ts 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 Kt administration resulted in resolution of the clinical symptoms. Screening of several family members on this mutatio n with an RFLP technique revealed 10 asymptomatic members who were heterozy gous for the mutation, confirming the autosomal recessive pattern of inheri tance of this disease. In 50 non-related normal subjects, the mutation was not found. This is the second time a missense mutation in the gamma -glutam yl carboxylase gene is described that has serious impact on normal hemostas is. (C) 2000 by The American Society of Hematology.