title: Genetic Epidemiology of Glucose-6-Phosphate Dehydrogenase Deficiency in the Arab World.
abstract: A systematic search was implemented using four literature databases (PubMed, Embase, Science Direct and Web of Science) to capture all the causative mutations of Glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDD) in the 22 Arab countries. Our search yielded 43 studies that captured 33 mutations (23 missense, one silent, two deletions, and seven intronic mutations), in 3,430 Arab patients with G6PDD. The 23 missense mutations were then subjected to phenotypic classification using in silico prediction tools, which were compared to the WHO pathogenicity scale as a reference. These in silico tools were tested for their predicting efficiency using rigorous statistical analyses. Of the 23 missense mutations, p.S188F, p.I48T, p.N126D, and p.V68M, were identified as the most common mutations among Arab populations, but were not unique to the Arab world, interestingly, our search strategy found four other mutations (p.N135T, p.S179N, p.R246L, and p.Q307P) that are unique to Arabs. These mutations were exposed to structural analysis and molecular dynamics simulation analysis (MDSA), which predicting these mutant forms as potentially affect the enzyme function. The combination of the MDSA, structural analysis, and in silico predictions and statistical tools we used will provide a platform for future prediction accuracy for the pathogenicity of genetic mutations.
authors.affiliation: Department of Integrative Biology, School of Biosciences and Technology, VIT University, Vellore, India.
authors.forename: C George Priya
authors.initials: CG
authors.lastname: Doss
authors.affiliation: College of Health Sciences, Biomedical Sciences Department, Qatar University, Doha, Qatar.
authors.forename: Dima R
authors.initials: DR
authors.lastname: Alasmar
authors.affiliation: College of Health Sciences, Biomedical Sciences Department, Qatar University, Doha, Qatar.
authors.forename: Reem I
authors.initials: RI
authors.lastname: Bux
authors.affiliation: Department of Integrative Biology, School of Biosciences and Technology, VIT University, Vellore, India.
authors.forename: P
authors.initials: P
authors.lastname: Sneha
authors.affiliation: College of Health Sciences, Biomedical Sciences Department, Qatar University, Doha, Qatar.
authors.forename: Fadheela Dad
authors.initials: FD
authors.lastname: Bakhsh
authors.affiliation: College of Health Sciences, Biomedical Sciences Department, Qatar University, Doha, Qatar.
authors.forename: Iman
authors.initials: I
authors.lastname: Al-Azwani
authors.affiliation: CIBER Pathophysiology of obesity and nutrition CB06/03, Carlos III Health Institute. Unidad de Gestion Clínica Intercentros de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga/Universidad de Málaga, 29009, Málaga, Spain.
authors.forename: Rajaa El
authors.initials: RE
authors.lastname: Bekay
authors.affiliation: College of Health Sciences, Biomedical Sciences Department, Qatar University, Doha, Qatar.
authors.forename: Hatem
authors.initials: H
authors.lastname: Zayed
mesh_terms: D018912:Arabs / Q000235:genetics*; D005954:Glucosephosphate Dehydrogenase / Q000737:chemistry / Q000235:genetics; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D056004:Molecular Dynamics Simulation; D009154:Mutation; D000072417:Protein Domains
chemical_list: D005954:Glucosephosphate Dehydrogenase