Factor XKetchikan: a variant molecule in which Gly replaces a Gla residue at position 14 in the light chain

To seek the possible molecular defect in a patient with deficient factor X plasma procoagulant activity, factor X gene exosn and splice junctions were subjected to heteroduplex analyses and sequencing. A mutation in exon 2 was confirmed as substitution of A by G at nucleotide position 206, coding for Gly instead of a Glu which is a normal precursor for gamma-carboxylated glutamic acid (Gla) at amino acid position 14. An abolished TaqI restriction site was used to indicate homozygosity of the defect, but occurrence of a gene deletion with attendant heterozygosity could not be excluded. The deletion of a Gla residue could affect the Ca(2+)-binding properties of factor X or confer a flexibility interfering with the interactive properties of the light chain. The defect could explain the decreased functional activity of circulating factor X and the mild bleeding tendency of the propositus.