Hemophiliacs A patients from Algeria without mutation or rearrangement in the F8 gene

Abstract

Hemophilia A (HA) is the most severe X-linked inherited bleeding disorder caused by hemizygous mutations in the F8 gene. Several F8 mutations are responsible of HA including intron 1 and 22 micro-inversions, large and small deletions, insertions, duplications, and point mutations. In a previous study, we determined the molecular causes of HA in 85% of patients group studied. However, no mutation were found in three unrelated patients origi-nating from Western Algeria. In the present study, we sought to characterize the molecular origin of HA in three patients by investigating rearrangements in the F8 gene using the MLPA method. Comparaison between case results and healthy controls showed absence of deletions or duplications in the F8 gene in these three hemophiliacs A patients. This finding has already been reported in many studies where any F8 mutation or rearrangement has been identified. Further analysis are required in order to determine the molecular origin of the disease in these families. It would be very interesting to look for deep intonic mutations and to study epigenetic mechanisms as well as DNA methylation and miRNAs.