Proven or Highly Probable Factor VII Arg304Gln (FVII Padua) Homozygous Defect: A Mutation that Occurred in Different Areas of the World Which Were Related or Unrelated With Known Forced or Spontaneous Migratory Patterns

Objective: to investigate the areas in which the Factor VII Padua Arg304Gln mutation has been reported and to identify its diffusion according to known migratory patterns. Patients, Methods: countries that showed the presence of at least 2 unrelated proven homozygotes and six heterozygotes were selected. These patients had to be studied by molecular biology techniques (Group A). Patients suspected to be cases of FVII Padua only on the basis of clotting tests were also gathered (Group B). The latter patients had to show the discrepancy in FVII assays between rabbit brain (low activity) vs human recombinant and Ox brain thromboplastins (normal activity). Results: there are 5 areas of the world that met the criteria, namely Mediterranean area, Iran, USA, Japan and Argentina. Some of these countries can be related because of ancient migratory patterns. Conclusions: It is likely that at least two independent main sources for the Arg304Gln Factor VII mutation, have occurred, namely the Mediterranean area and Japan pattern. The observation that several heterozygotes for this mutation have been found in West Africa suggests that the homozygotes seen in the USA only among African-Americans are the result of the "forced" emigration that occurred in the past.