PROTHROMBIN-PADUA-I - INCOMPLETE ACTIVATION DUE TO AN AMINO-ACID SUBSTITUTION AT A FACTOR-XA CLEAVAGE SITE

An individual and an affected brother previously identified as having the variant prothrombin Padua I were studied in order to identify underlying genetic defects. A heterozygous mutation in the prothrombin gene exon 8 was identified as substitution of A for G at nucleotide position 7312 (Arg(271) (CGT) to His (CAT)). An abolished RsaI restriction site was used to confirm heterozygosity for the defect. Lack of the requisite cleavage of the His(271)-Thr(272) bond in prothrombin Padua I could prevent release of fragment 2 and block the conversion of the intermediate meizothrombin des fragment 1 to alpha-thrombin, providing an explanation of reduced potential for clotting activity and for the observed mild bleeding tendency.