Screening of the most common MEFV mutations in a large cohort of Egyptian patients with Familial Mediterranean fever

Zarouk, Waheba A.; El-Bassyouni, Hala T.; Ramadan, Abeer; Fayez, Alaaeldin; Esmaiel, Nora N.; Foda, Bardees M.; Kobiesy, Maha M.; Zekry, May E.; Lotfy, Randa; Shehata, Ghada M.

doi:10.1016/j.genrep.2018.01.008

Cited by 9 publications

(9 citation statements)

References 69 publications

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“…The M694V mutation could not be identified in this study in agreement with the results reported in previous work. 18 Moreover, there was no significant difference in S100A12 levels between cases with heterozygous M694I mutation and those with other types of mutations. This may be due to the small number of FMF patients in the subgroups.…”

Section: Discussionmentioning

confidence: 84%

Clinical Implications of S100A12 and Resolvin D1 Serum Levels, and Related Genes in Children with Familial Mediterranean Fever

Abdallah

Ibrahim

Thomas

et al. 2021

Journal of Child Science

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The aim of this article was to study the role of S100A12 and resolvin D1-related genes and serum levels in the diagnosis and detection of subclinical inflammation in children with familial Mediterranean fever (FMF) during the quiescent stage of the disease. Seventy-eight children with FMF during the silent state and 60 healthy control were studied. Serum S100A12 and resolvin D1 were quantitatively measured using enzyme-linked immunosorbent assay. In addition, the levels of C-reactive protein, erythrocyte sedimentation rate, and hemoglobin were determined. The clinical severity was evaluated. The link between the Mediterranean fever (MEFV) gene and the genes related to the two studied biomarkers was also assessed. Correlation between S100A12 and resolvin D1 and the clinical severity was assessed. The mean serum levels of S100A12 and resolvin D1 were 847.4 and 793.3, respectively, which were highly significantly increased (p = 0.001) compared with the controls (324.3 and 235.1, respectively). The receiver operating characteristic curve test showed that S100A12 had a sensitivity of 97.4% and specificity of 80% with cutoff value of 529.5, while resolvin D1 showed a sensitivity of 100% and specificity of 50% with cutoff value of 231.2. A correlation was detected between the clinical severity and S100A12 and resolvin D1. This study delineated that S100A12 and resolvin D1 are sensitive biomarkers to detect the degree of inflammation in children with FMF during the silent period. Consequently, we recommend adjusting the colchicine dose to ameliorate the disease's symptoms and to improve the quality of life in these patients.

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Section: Discussionmentioning

confidence: 84%

Clinical Implications of S100A12 and Resolvin D1 Serum Levels, and Related Genes in Children with Familial Mediterranean Fever

Abdallah

Ibrahim

Thomas

et al. 2021

Journal of Child Science

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“…In addition, while p.M694I and p.V726A are known to be common among Arab populations in the Middle East [44], p.M680I is common in Turkish FMF patients [29,30]. The frequency of these mutations is not the same among North African countries [44][45][46][47][48][49]. In total, it seems that the order of five most common MEFV gene mutations among Iranian FMF patients is most similar to that observed in Middle Eastern Arab populations [44].…”

Section: Discussionmentioning

confidence: 88%

Spectrum of MEFV gene mutations in 4,256 familial Mediterranean fever patients from Iran: a comprehensive systematic review

Alibakhshi

Ghadiri

Khamooshian

et al. 2022

Egypt J Med Hum Genet

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Background Familial Mediterranean fever (FMF), known as a disease with a high prevalence rate among Armenian, Turkish, Jewish, and Arab descent populations, occurs as a result of pathogenic variants in mediterranean fever (MEFV) gene. The aim of this study was to review the spectrum and frequency of MEFV gene mutations reported among Iranian FMF patients. Methods After performing a systematic review of the literature and implementation of inclusion and exclusion criteria, 16 articles published between 2004 and 2020, involving 4,256 Iranian FMF patients, were included. Results A total of 38 different MEFV gene mutations were identified. The most common mutations among Iranian FMF patients were: p.M694V (c.2080A > G) (20.27%), p.E148Q (c.442G > C) (10.27%), p.V726A (c.2177T > C) (8.24%), p.M680I (both c.2040G > C and c.2040G > A) (7.20%), p.R761H (c.2282G > A) (2.1%), and p.M694I (c.2082G > A) (2. 1%). The frequencies of these mutations were significantly different in different parts of the country. Conclusions The ranks and frequencies of p.M694V, p.E148Q, p.V726A, p.M680I, and p.M694I in our population were closer to those observed in the Mediterranean countries, especially in the Middle Eastern Arab populations. Although some comprehensive studies have been performed on Azeri Turkish patients living in northwestern Iran, studies in other areas, especially in eastern Iran, have been very limited. One reason for this observation could be due to the low frequency of FMF patients in those areas. Regardless of the reason for this, the exact spectrum and frequency of MEFV gene mutations in Iranian FMF patients remain unclear. Therefore, comprehensive future studies in different parts of the country are recommended.

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“…In the present study, we aimed to postulate the possible pathogenicity cascade of the studied B30.2 domain variants to extend our previous published work of Zarouk et al [ 10 ]. Applied bioinformatics tools, based on protein structure, alternative splicing, and molecular mechanics simulation were implemented.…”

Section: Introductionmentioning

confidence: 85%

“…Based on our previous published literature [ 10 ], we proceeded with the classification of B30.2/SPRY (580-775aa) variants to test its implications on FMF pathogenicity using different computational biology algorithms and molecular mechanic’s study. The 3D of the B30.2/SPRY domain was retrieved from PDB [ 11 ] under code 2wl1 (x-RAY; 1.35A, 586-776aa).…”

Section: Methodsmentioning

confidence: 99%

Dynamic disequilibrium-based pathogenicity model in mutated pyrin’s B30.2 domain—Casp1/p20 complex

Fayez

Eldeen

Zarouk

et al. 2022

Journal of Genetic Engineering and Biotechnology

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Background The B30.2 variants lead to most relevant severity forms of familial Mediterranean fever (FMF) manifestations. The B30.2 domain plays a key role in protein-protein interaction (PPI) of pyrin with other apoptosis proteins and in regulation the cascade of inflammatory reactions. Pyrin-casp1 interaction is mainly responsible for the dysregulation of the inflammatory responses in FMF. Lower binding affinity was observed between the mutant B30.2 pyrin and casp1 without the release of the complete pathogenicity mechanism. The aim of this study was to identify the possible effects of the interface pocked residues in B30.2/SPRY-Casp1/p20 complex using molecular mechanics simulation and in silico analysis. Results It was found that Lys671Met, Ser703Ile, and Ala744Ser variants led mainly to shift of the binding affinity (∆G), dissociation constant (Kd), and root mean square deviation (RMSD) in B30.2/SPRY-Casp1/p20 complex leading to dynamic disequilibrium of the p20-B30.2/SPRY complex toward its complex form. The current pathogenicity model and its predicted implementation in the relevant colchicine dosage were delineated. Conclusion The molecular mechanics analysis of B30.2/SPRY-p20 complex harboring Lys671Met, Ser703Ile, and Ala744Ser variants showed dynamic disequilibrium of B30.2/SPRY-casp1/p20complex in context of the studied variants that could be a new computational model for FMF pathogenicity. This study also highlighted the specific biochemical markers that could be useful to adjust the colchicine dose in FMF patients.

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Screening of the most common MEFV mutations in a large cohort of Egyptian patients with Familial Mediterranean fever

Cited by 9 publications

References 69 publications

Clinical Implications of S100A12 and Resolvin D1 Serum Levels, and Related Genes in Children with Familial Mediterranean Fever

Clinical Implications of S100A12 and Resolvin D1 Serum Levels, and Related Genes in Children with Familial Mediterranean Fever

Spectrum of MEFV gene mutations in 4,256 familial Mediterranean fever patients from Iran: a comprehensive systematic review

Dynamic disequilibrium-based pathogenicity model in mutated pyrin’s B30.2 domain—Casp1/p20 complex

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