COMBINED FACTOR-V AND FACTOR-VIII DEFICIENCY - THE SOLUTION

Combined deficiency of coagulation factor V and factor VIII is an auto somal recessive disorder which has been observed in a number of popula tions around the world. However, this disease appears to be most commo n in the Mediterranean basin, particularly in Jews of Sephardic and Mi ddle Eastern origin living in Israel. We have taken a positional cloni ng approach toward identifying the gene responsible for this disorder. We initially studied 14 affected individuals from nine unrelated Jewi sh families using a panel of polymorphic genetic markers spaced throug hout the human genome. The combined factors V and Vm deficiency gene w as mapped to a locus on the long arm of chromosome 18 with a maximal L OD score of 13.22. A detailed genetic analysis identified two distinct haplotypes among these families, suggesting two independent founders or, alternatively, a single ancient founder with a more recent split o f these subpopulations. Further work to identify and characterize the gene responsible for combined factors V and VIII deficiency should pro vide important insights into the biosynthesis of these homologous prot eins.