![]() ![]() This study aims to identify F8 gene mutations among Egyptian HA patients.ĭNA samples from 60 HA patients were screened for int22 and int1 rearrangements using simplified inverse shifting PCR (IS‐PCR) followed by exon 14 sequencing. ![]() F8 rearrangements involving intron 22 (int22) and intron 1 (int1) account for almost half of severe HA phenotype also a hotspot exon 14 provides numerous mutational patterns. Hemophilia A (HA) is an inherited X‐linked recessive coagulation disorder caused by factor VIII (F8) deficiency. In silico methods, despite being useful in providing informations about effects of mutations, can also serve as a first-pass filter for experimental studies. This study demonstrates the effectiveness of the combined use of several in silico methods to assess the deleterious effects of novel mutations. The novel missense mutation c.2189G> A (p.Cys711Tyr) is responsible of the rupture of the disulfide bridge (Cys630-Cys711) causing a FVIII protein destabilization. The c.200A> C introduces a neutral residue to the protein structure which could be responsible of hydrogen bonds loss causing improper folding of the FVIII protein. Concerning the missense mutation c.200A> C (p.Lys48Thr), physicochemical changes between Lysine and Threonine were predicted to have deleterious effects on both structure and function of the protein. Our analysis showed that the splice site mutation c.5219+1G>T is responsible of exon 14 skipping which cause the deletion of the protein B domain. ![]() ![]() In the present study, we aimed to analyze the structural and functional impact of novel F8 gene mutations, previously identified in the Algerian population, through several in silico methods : HSF, ESE Finder, I-Mutant 2, SIFT, Polyphen 2, Align GVGD, ConSurf and Project Hope. These mutations are responsible for causing hemophilia A, an inherited bleeding disorder resulting from a reduced or absence of the coagulant FVIII protein activity. Since the publication of the F8 gene sequence, a large number of F8 gene mutations has been identified. ![]()
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January 2023
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