Screening for genetic variations in factor VIII gene in patients with haemophilia A in Al-Diwaniyah City

Abstract

Haemophilia is a congenital haemorrhagic disorder caused by defect in human genetic content. Males get the disease while females are carriers. This study aimed to identify common FVIII gene mutations in Iraqi patients by molecular analysis and to determine whether mutations are inherited or not. This study included 50 Iraqi patients with haemophilia A, 35 of whom were male haemophilia patients and 15 of whom were carrier mothers. After determining the purity and concentration of the extracted DNA, selected areas of the FVIII gene, including exons 18, 22, 23, and 24 and intron 22, were amplified. Sequencing of all exons and intron 22 was conducted in all patients and controls. Sequencing analysis revealed that many mutations were distributed among the exons (18, 22, 23, and 24) and intron 22; most of the identified mutations were point mutations in exons, predominantly in exon 24. Exon 18 mutations were detected in one male and one mother as a carrier. Exon 22 mutations were detected in four patients, and exon 23 mutations were detected in two males and two carrier mothers. Exon 24 mutations were detected in 12 haemophilia patients and two carrier mothers. Additionally, seven inversion mutations were detected in haemophilia patients. The results also revealed positive correlations between disease severity and mutations in intron 22 and exon 24. This study concluded that many mutations were highly frequent of insertion and deletion occurred in FVIII genes and the patients’ mothers (carriers) were identical with patient’s sons.