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 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.
James
H L
HL
Department of Biochemistry, University of Texas Health Center at Tyler 75710.
Kim
D J
DJ
Zheng
D Q
DQ
Girolami
A
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002648:Child; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification; D015252:Deoxyribonucleases, Type II Site-Specific; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D015951:Factor Xa / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011516:Prothrombin / Q000737:chemistry* / Q000235:genetics*
D011516:Prothrombin; D004247:DNA; D015252:Deoxyribonucleases, Type II Site-Specific; C040158:GTAC-specific type II deoxyribonucleases; D015951:Factor Xa