Identification of Factor VIII Gene Mutations in Patients with Haemophilia A

Abstract

The study is aimed to detect the primary mutations of the FVIII gene among Iraqi patients using molecular analysis and to identify the relationships between these mutations and the severity of the disease. The study involved twenty-five patients with haemophilia type A, eighteen of those patients were males, and seven of them were mothers with disease carriers, from seven families but un-related. The extracted DNA determined by the concentration and purity and then after the amplification of selected parts of the FVIII gene involving intron 22 and exons 18, 22, 23, 24 were done. Sequencing of these exons and introns were done for all patients and control subjects. Sequencing analysis showed that the majority of mutations were "point mutations" in exons, mostly in exon 24. In contrast, the mutations in exon 18 were identified in one male in addition to one carrier mother. The mutations in exon 22 were identified in four patients, and the mutation in exon 23 was identified in two males in addition to two carrier mothers. The mutations in exon 24 were identified in twelve patients with haemophilia in addition to two carrier mothers. Moreover, the numbers of identified inversion mutations in the study were seven in hemophilic patients. The study showed there was a direct relationship between the severity of disease and the mutations in exon 24 and intron 22. So, the ultimate conclusion of this study showed that the most common mutations in Iraqi hemophilic patients were exon 24 mutations and followed by intron 22 mutations. The majority of these mutations occurred in severe cases of haemophilia.