The duplication breakpoints are localized to the directly-oriented LCRs int22h1 located within intron 22 of the F8 gene and int22h2 situated ~0.5 kb telomerically to int22h1. A third homologous region int22h-3 is located ~0.6 kb telomerically to int22h1. Genomic inversions between int22h-1 and either int22h-2 or int22h-3, disrupts the F8 gene in nearly half of severe hemophilia A cases [19]. The gene discussed is F8; the disease is hemophilia A.