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.

Structural Analysis of G1691S Variant in the Human Filamin B Gene Responsible for Larsen Syndrome: A Comparative Computational Approach

“…B). The loss of hydrophobic and negatively charged interaction might lead to loss of thermodynamics stability [George et al, ; Doss et al, ]. This supports that the loss of hydrophobic residue (VAL90) and negatively charged residue (ASP91) might serve the reason for destabilization of protein due to G1691S.…”

“…The number of variants responsible for genetic disorders are being deposited in public databases is increasing rapidly. Recent technological advances and cost‐effectiveness in genomic analysis have largely involved in understanding the relationship between the disease and missense variants [Doss et al, ]. The distinction between the variants which affect the protein structure and function from those who have little or no effect from larger pool of data obtained through experimental techniques is highly tedious [Doss et al, ].…”

“…Recent technological advances and cost‐effectiveness in genomic analysis have largely involved in understanding the relationship between the disease and missense variants [Doss et al, ]. The distinction between the variants which affect the protein structure and function from those who have little or no effect from larger pool of data obtained through experimental techniques is highly tedious [Doss et al, ]. The prioritization of pathogenic variants and studying their structural influence at molecular level through computational approaches has become the future step for drug therapeutic approach [George et al, ; Doss et al, ; Thirumal et al, ].…”

“…Using multiple in silico prediction tools could increase the reliability of the predictions of variant pathogenicity [Capriotti et al, ; Bendl et al, ; Doss et al, ]. These combinations were used in earlier studies to prove the potential impact of missense variants in other proteins such as Canavan disease, MODY2, PIK3CA, TITIN, and G6PD [George et al, ; Ali et al, ; Doss et al, ; Sudhakar et al, ; Thirumal et al, ; Zaki et al, ].…”

Retinopathy of Type 1 Diabetes in Arab Countries: Systematic Review and Meta-Analysis

“…Our subgroup and meta-regression analysis did not indicate any significant difference by period, region, or sample size; however, heterogeneity was still observed within subgroups. Consanguinity is part of the endogenous Arab culture, with a significant high prevalence of first-cousin marriage [29], which is still rising in some Arab countries [30], which is found to be responsible for the high prevalence of genetic diseases in the Arab countries [8,9,[31][32][33]. Few studies (n = 5) reported the consanguinity [21,26,27,30,34] (Table 1).…”