Study of mutations in Jordanian patients with haemophilia A: identification of five novel mutations

Abstract

Haemophilia A (HA) is an X-linked recessive bleeding disorder caused by mutations in the factor VIII gene (F8), which encodes factor VIII (FVIII) protein, a plasma glycoprotein, that plays an important role in the blood coagulation cascade. In the present study, our aim was to identify F8 gene mutations in HA patients from Jordan. One hundred and seventy-five HA patients from 42 unrelated families were included in this study. Among these patients, 117 (67%) had severe HA, 13 (7%) had moderate HA and 45 (26%) had mild HA. Severe patients were first tested for intron-22 inversion using long range polymerase chain reaction (PCR), then negative patients were tested for intron-1 inversion using PCR. Sequencing for the entire F8 gene was performed for all severe HA patients who were found negative for intron-22 and -1 inversions and it was also performed for moderate and mild HA patients. HA causative mutations were identified in all patients. Intron-22 and -1 inversions were detected in 52% and 2% of families respectively. Beside these two mutations, 19 different mutations were identified, which include 15 missense and four frameshift mutations. Five novel mutations were identified including one frameshift and four missense mutations. No large deletions or nonsense mutations were detected in patients who participated in this study. Only 17 patients with severe HA were found positive for FVIII inhibitors. The data presented will play an important role for genetic counselling and health care of HA patients in Jordan.

Identification of factor VIII gene mutations in patients with severe haemophilia A in Venezuela: identification of seven novel mutations

“…We detected 25 different mutations as causative for sHA, with the F8 intron 22 inversion as the most common mutation (41%), which is consistent with other reports that show that this inversion affects approximately 40–50% of the cases [7,12,21–25]. The intron 1 inversion frequency varies between populations, ranging from 0% to 5% in patients with sHA [5,12,22,23,25–27]. In our study, we did not detect this mutation, which is in agreement with some of the above studies [23,26,27].…”

Mutation Screening of the Factor VIII Gene in Hemophilia A in Saudi Arabia: Two Novel Mutations and Genotype-Phenotype Correlation

“…The aim of this study was to investigate mutations in the factor-VIII gene in Saudi Arabian population. There are few previous reports about hemophilia A screening in the Middle Eastern population, specifically in Saudi Arabian Population by Owaidah, et al in Lebanese population by Khayat, et al in Tunisian population by Elmahmoudi, et al [50] and in Jordanian population by Awidi, et al [31]. In the present study mutational screenings of factor VIII gene sequencing analysis, and intronic rearrangements such as, inv-1 and inv-22 analysis were performed in the hemophilia A patients of Saudi Arabian population.…”

“…Several studies are available in literature describing the mutations in factor VIII gene, from many ethnic groups and different populations [16,17,25,29,30]. Recently, some reports were published from Middle Eastern countries also describing factor VIII gene mutations [31][32][33][34]. However, the spectrum and nature of common mutations causing hemophilia A in Arab population specifically in Saudi Arabs is not clear.…”

Variabilitas Pola Perdarahan Anak Hemofilia A yang Mendapat Terapi On-demand di Rumah Sakit Cipto Mangunkusumo

“…28,23 Pada ras Asia, prevalensnya jauh lebih rendah yaitu 1,4−10,4%. [29][30][31][32] Pada penelitian ini, prevalens inhibitor faktor VIII adalah 7,3% dan 87,5% diantaranya ditemukan pada hemofilia A berat. Selain faktor ras, pola terapi on demand, dosis terapi yang relatif rendah dan konsentrat faktor VIII yang berasal dari plasma (plasma derived clotting factor concentrate) merupakan faktor-faktor yang dapat berkontribusi terhadap rendahnya prevalens inhibitor pada subjek penelitian kami.…”