INVERSION MUTATION AS A MAJOR CAUSE OF SEVERE HEMOPHILIA-A IN ITALIANPATIENTS

We investigated the presence of a recombinant event between the F8A ge ne located in intron 22 of the factor VIII gene and the two additional copies of F8A lying 500 Kb upstream of FVIII in severe hemophilic pat ients. The genomic DNA of 146 unrelated Italian patients with severe h emophilia A (HA) was hybridized with an F8A gene probe to detect the a bnormal band patterns. A recombinant event was found in 71/146 patient s, confirming the high incidence of this mutation in the Italian hemop hilic population also. We conclude that the high frequency of the muta tion in HA subjects allows us to make a direct and safe diagnosis in a bout 50% of our families without resorting to RFLP analysis. (C) 1997, Ferrata Storti Foundation.