Mutation Analysis of F8 Gene and Phenotypic Characterization of Hemophilia A

Abstract

Background Hemophilia A HA is a congenital bleeding disorder caused due to deficiency of Factor VIII clotting protein in the blood. It follows an X-linked recessive mode of inheritance.Aim In the present study clinical and haematological manifestations have been analysed and their correlation with molecular mutations in patients with haemophilia A has been tested.Methods A total of 90 HA patients were included in the study. Plasma coagulation test PT APTT and correction study factor VIII assay inhibitors screening test and quantification tests were done for all the patients. Mutation analysis was carried out to evaluate the molecular alteration in F8 gene only on exon.Results Among the 90 Hemophilia A patients included 3 3.3 were diagnosed as mild 15 16.6 as moderate and 72 80 were diagnosed as severe hemophilic patients. Positive family history was observed in 62 68.8 patients while 35 38.8 were born to consanguineous couples. Joint bleeding 88.8 was most commonly observed followed by mucocutaneous bleeding 66.6 dental bleeding 48.8 genitourinary bleeding 16.6 gastrointestinal bleeding 15.5 muscle bleeding 14.4 and intracranial bleeding 10. Around 13 14.4 HA patients developed inhibitors among which five were of low titer and eight were of high titer. Mutation analysis of 90 HA patients recorded a total of 21 mutations including 52.4 missense mutations 23.8 nonsense mutations 23.8 frameshift mutations. No novel mutation was noted.Conclusion The present study showed several missense mutations in severe HA patients. This result is a slight deviation from the reports of earlier Indian studies which could be due to difference in geographic population ethnicity and other factors. Hence a detailed genotype and phenotype screening in relation to severity and development of inhibitors is much essential for timely monitoring and appropriate treatment of Hemophilia A.