Prothrombin Padua I: incomplete activation due to an amino acid substitution at a factor Xa cleavage site.

Abstract

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 7,312 (Arg271 (CGT) to His (CAT)). An abolished RsaI restriction site was used to confirm heterozygosity for the defect. Lack of the requisite cleavage of the His271-Thr272 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.

• Authors: H L James, D J Kim, D Q Zheng, A Girolami
• Journal: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis (Blood Coagul Fibrinolysis) Vol. 5 Issue 5 Pg. 841-4 (Oct 1994) ISSN: 0957-5235 [Print] England
• PMID: 7865694 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Prothrombin
• DNA
• Deoxyribonucleases, Type II Site-Specific
• GTAC-specific type II deoxyribonucleases
• Factor Xa

Topics

• Amino Acid Sequence
• Base Sequence
• Binding Sites
• Child
• DNA (chemistry, isolation & purification)
• Deoxyribonucleases, Type II Site-Specific
• Electrophoresis, Polyacrylamide Gel
• Exons
• Factor Xa (metabolism)
• Heterozygote
• Humans
• Male
• Molecular Sequence Data
• Mutation
• Prothrombin (chemistry, genetics)