Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency (PID), characterized by fatal opportunistic infections. The ADA gene encodes adenosine deaminase, an enzyme that catalyzes the irreversible deamination of adenosine and deoxyadenosine in the catabolic pathway of purine. Mutations of the ADA gene have been identified in patients with severe combined immunodeficiency. In this study, we performed a bioinformatics analysis of the human ADA gene to identify potentially harmful nonsynonymous SNPs and their effect on protein structure and stability. Using eleven prediction tools, we identified 15 nsSNPs (H15D, H15P, H17Q, H17Y, D19N, T26I, G140E, C153F, A183D, G216R, H258Y, C262Y, S291L, S291W, and K34OE) as harmful. The results of ConSurf's analysis revealed that all these nsSNPs are localised in the highly conserved positions and affect the structure of the native proteins. In addition, our computational analysis showed that the H15D, G140E, G216R, and S291L mutations identified as being associated with severe combined immunodeficiency affect protein structure. Similarly, the results of the analyses of Rmsd, Rmsf, and Rg showed that all these factors influence protein stability, flexibility, and compaction with different levels of impact. This study is the first comprehensive computational analysis of nsSNPs of the ADA gene. However, functional analyses are needed to elucidate the biological mechanisms of these polymorphisms in severe combined immunodeficiency.

RRM2B gene encodes ribonucleoside-diphosphate reductase subunit M2 B, the p53-inducible small subunit (p53R2) of ribonucleotide reductase (RNR), an enzyme catalyzing dNTP synthesis for mitochondrial DNA. Defects in this gene may cause severe mitochondrial disease affecting mainly the nervous system. This study is aimed at examining the effect of deleterious nonsynonymous SNP (nsSNP) on the structure of the RRM2B protein, using a variety of prediction tools followed by a molecular modeling analysis. After using 13 algorithms, 19 nsSNPs were predicted deleterious. Among these variants, 18 decreased the protein stability and 16 were localized in very highly conserved regions. Protein 3D structure analysis showed that 18 variants changed amino acid interactions. These results concur with what has been found in experimental trials; 7 deleterious nsSNPs were previously reported in patients suffering from genetic disorders affecting the nervous system. Thus, our study will provide useful information to design more efficient and fast genetic tests to find RRM2B gene mutations.

BackgroundDuring Ramadan, many patients with diabetes, renal, cardiovascular, gastrointestinal diseases, headaches, and epilepsy choose to fast even against their doctor's advice. The impact of this intermittent fasting on health and disease could be different in men and women. The aim of this study was to determine the effect of sex as a factor in diseases outcomes of patients who opt to fast during Ramadan.Main BodyThe articles included in this study reported data on six diseases: diabetes, renal, cardiovascular, gastrointestinal diseases, headaches, and epilepsy. A systematic search was performed on PubMed and Scopus for observational and clinical studies mentioning Ramadan, diabetes, renal, cardiovascular, gastrointestinal diseases, headaches, and epilepsy in both men and women. Data was extracted by two independent reviewers using a standardized data-collection form. From 381 original articles, 38 studies were selected, including 25,023 patients of which 44.4% were women. Sex-based differences were reported by 18 studies for several variables such as body mass index, blood glucose, the frequency of hypoglycemia, renal colic, mortality, thrombosis, and gastrointestinal diseases in patients fasting during Ramadan. Most of the differences between men and women were reported both in the baseline period before Ramadan and during Ramadan. Indeed, during the period outside Ramadan, the frequency of renal colic, cardiovascular, gastrointestinal diseases, were higher in men; while body mass index, Thrombosis, and headache were higher in women. In the remaining 21 studies, it was reported that the sex factor was not associated with the effect of Ramadan fasting in the frequency and other outcomes of these diseases.ConclusionCurrently, small attention is paid to sex as a determinant factor in patients while fasting during Ramadan. There appeared to be differences in the frequency and incidence of diseases in men and women during Ramadan. Closer attention to sex differences regarding the frequency and the progression of the diseases during fasting may help to improve patient care, especially to benefit those patients willing to fast during Ramadan.

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