Blood, Vol. 95 No. 2 (January 15), 2000:
pp. 711-714
BRIEF REPORT
Prothrombin San Antonio: a single amino acid substitution at a
Factor Xa activation site (Arg320 to His) results in
dysprothrombinemia
William Y. Sun,
Melissa C. Burkart,
Joseph R. Holahan, and
Sandra J. F. Degen
From the Division of Developmental Biology, Children's Hospital
Research Foundation, Cincinnati, OH; and South Texas Oncology and
Hematology Associates, P.A., San Antonio, TX.
Three members of a San Antonio, Texas, family were identified with
prothrombin activity levels half the normal level but to have normal
levels of antigen. All exons of the prothrombin gene from the proband
were sequenced. A G-to-A mutation at nucleotide 7543 was found that
resulted in the substitution of His for Arg at residue 320. The
Arg320-Ile321 bond is 1 of 2 sites in prothrombin cleaved by Factor Xa
in the prothrombinase complex to form thrombin. Substitution of His for
Arg at this site resulted in the blockage of Factor Xa cleavage,
forming a dysfunctional molecule. The proband, her mother, and her
maternal aunt were found to be heterozygous for this mutation. This is
the first known observation of an amino acid substitution at this site
that resulted in dysprothrombinemia.
