Aberrant F8 gene intron 1 inversion with concomitant duplication and deletion in a severe hemophilia A patient from Southern Italy

Abstract Intron 1 and intron 22 inversions (inv1 and inv22) represent the most prevalent mutations in the F8 gene (F8) (1-5% and 40-45%, respectively) causative of severe haemophilia A (HA) [1]. These alterations result from intrachromosomal recombination between intronic regions (int1h-1 and int22h-1, respectively) and their homologous extragenic copies in telomeric position (int1h-2 and int22h-2/3, respectively) [1]. Inv1 causes an altered F8 structure with the translocation and inversion of the 5' region including exon 1 in the extragenic site, giving rise to 2 chimeric mRNAs: one containing the promoter and first exon of the F8 followed by some exons of the VBP1 gene; the other one formed by the promoter and coding sequences of the C6.1A gene joined to a part of the intron 1 and exons 2-26 of the F8 [2]. © 2012 International Society on Thrombosis and Haemostasis.