Gly319 -> Arg substitution in the dysfunctional prothrombin Segovia

The molecular defect of a congenitally dysfunctional form of prothrombin, p rothrombin Segovia, was identified in a patient with a severe bleeding tend ency, reduced prothrombin coagulant activity, and normal antigen level. Nuc leotide sequencing of amplified DNA revealed a G-A change at nucleotide 753 9 of exon 9 of the prothrombin gene. This resulted in the substitution of G ly 319 by Arg, The proband was homozygous for this mutation, his father and brother were heterozygous. Mle surmised that the substitution, which occur s near the site of cleavage of prothrombin by factor Xa (Arg320-Ile321), al tered the conformation of the protein making the cleavage site inaccessible .