Summary
We have identified a patient with a dysfunctional prothrombin that we have designated
Prothrombin Frankfurt. The proband was characterized by a prothrombin activity level
of 13% and 20% compared to normal controls using two different assays with a normal
prothrombin antigen level of 91% of normal controls. The genetic defect responsible
for the abnormal prothrombin activity was determined by the polymerase chain reaction
followed by single-strand conformation polymorphism (PCR-SSCP) analysis and by DNA
sequence analysis of the human prothrombin gene. Substitution of a C for an A at nucleotide
10177 in the human prothrombin gene of the proband was identified, which results in
the replacement of Glu-466 by Ala. The proband and one sister were homozygous for
this mutation. Both parents, as well as one brother, were found to be heterozygous
for this mutation. The same amino acid substitution was previously identified to be
responsible for the dysfunctional protein Prothrombin Salakta and was hypothesized
to result in altered substrate specificity. Four polymorphisms were also identified
in the prothrombin gene from the proband when compared to the published sequence at
nucleotides 554, 4048, 4272 and 10253.
