Novel Deleterious nsSNPs within MEFV Gene that Could Be Used as Diagnostic Markers to Predict Hereditary Familial Mediterranean Fever: Using Bioinformatics Analysis

Background. Familial Mediterranean Fever (FMF) is the most common autoinflammatory disease (AID) affecting mainly the ethnic groups originating from Mediterranean basin. We aimed to identify the pathogenic SNPs in MEFV by computational analysis software. Methods. We carried out in silico prediction of structural effect of each SNP using different bioinformatics tools to predict substitution influence on protein structure and function. Result. 23 novel mutations out of 857 nsSNPs are found to have deleterious effect on the MEFV structure and function. Conclusion. This is the first in silico analysis of MEFV gene to prioritize SNPs for further genetic mapping studies. After using multiple bioinformatics tools to compare and rely on the results predicted, we found 23 novel mutations that may cause FMF disease and it could be used as diagnostic markers for Mediterranean basin populations.

Download Full-text

Novel deleterious nsSNPs within MEFV gene that could be used as Diagnostic Markers to Predict Hereditary Familial Mediterranean Fever: Using bioinformatics analysis

10.1101/424796 ◽

2018 ◽

Author(s):

Mujahed I. Mustafa ◽

Tebyan A Abdelhameed ◽

Fatima A. Abdelrhman ◽

Soada Ahmed Osman ◽

Mohamed A. Hassan

Keyword(s):

Familial Mediterranean Fever ◽

In Silico ◽

Mediterranean Basin ◽

Mefv Gene ◽

Structure And Function ◽

Diagnostic Markers ◽

Novel Mutations ◽

Bioinformatics Tools ◽

Mediterranean Fever ◽

And Function

AbstractBackgroundFamilial Mediterranean Fever (FMF) is the most common auto inflammatory disease (AID) affecting mainly the ethnic groups originating from Mediterranean basin, we aimed to identify the pathogenic SNPs in MEFV by computational analysis software.MethodsWe carried out in silico prediction of structural effect of each SNP using different bioinformatics tools to predict substitution influence on protein structure and function.Result23 novel mutations out of 857 nsSNPs that are found to be deleterious effect on the MEFV structure and function.ConclusionThis is the first in silico analysis in MEFV gene to prioritize SNPs for further genetic mapping studies. After using multiple bioinformatics tools to compare and rely on the results predicted, we found 23 novel mutations that may cause FMF disease and it could be used as diagnostic markers for Mediterranean basin populations.

Download Full-text

In silico analysis ofIDH3Agene revealed Novel mutations associated with Retinitis Pigmentosa

10.1101/554196 ◽

2019 ◽

Author(s):

Thwayba A. Mahmoud ◽

Abdelrahman H. Abdelmoneim ◽

Naseem S. Murshed ◽

Zainab O. Mohammed ◽

Dina T. Ahmed ◽

...

Keyword(s):

Retinitis Pigmentosa ◽

In Silico ◽

In Silico Analysis ◽

Photoreceptor Cells ◽

Structure And Function ◽

Novel Mutations ◽

Inherited Disorders ◽

Bioinformatics Tools ◽

And Function ◽

Silico Analysis

AbstractBackgroundRetinitis Pigmentosa (RP) refers to a group of inherited disorders characterized by the death of photoreceptor cells leading to blindness. The aim of this study is to identify the pathogenic SNPs in the IDH3A gene and their effect on the structure and function of the protein.Methodwe used different bioinformatics tools to predict the effect of each SNP on the structure and function of the protein.Result20 deleterious SNPs out of 178 were found to have a damaging effect on the protein structure and function.Conclusionthis is the first in silico analysis of IDH3A gene and 20 novel mutations were found using different bioinformatics tools, and they could be used as diagnostic markers for Retinitis Pigmentosa.

Download Full-text

The Association between SLC25A15 Gene Polymorphisms and Hyperornithinemia-hyperammonemia-homocitrullinuria Syndrome: Using In Silico Analysis

10.1101/786301 ◽

2019 ◽

Author(s):

Nuha A. Mahmoud ◽

Dina T. Ahmed ◽

Zainab O. Mohammed ◽

Fatima A. Altyeb ◽

Mujahed I. Mustafa ◽

...

Keyword(s):

In Silico ◽

Autosomal Recessive ◽

Urea Cycle ◽

In Silico Analysis ◽

Structure And Function ◽

Medical Testing ◽

Bioinformatics Tools ◽

And Function ◽

Silico Analysis ◽

Selection Of

BackgroundHyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is an autosomal recessive inborn error of the urea cycle. It is caused by mutations in the SLC25A15 gene that codes the mitochondrial ornithine transporter. The aim of this study is to detect and identify the pathogenic SNPs in SLC25A15 gene through a combination set of bioinformatics tools and their effect on the structure and function of the protein.MethodsThe deleterious SNPs in SLC25A15 are detected by various bioinformatics tools, with addition to identifying their effects on the structure and function of this gene.Results20 deleterious SNPs out 287of were found to have their own damaging effects on the structure and function of the SLC25A15 gene.ConclusionThis study is the first in silico analysis of SLC25A15 using a selection of bioinformatics tools to detect functional and structural effects of deleterious SNPs. Finding the pathogenic SNPs is a promising start to innovate new, useful SNP diagnostic markers for medical testing and for safer novel therapies specifically targeting mutant SLC25A15.

Download Full-text

In silicoanalysis of coding SNPs and 3′-UTR associated miRNAs inDCAF17gene that may affect the regulation and pathogenesis of Woodhouse-Sakati Syndrome

10.1101/601310 ◽

2019 ◽

Author(s):

Abdelrahman H. Abdelmoneim ◽

Asia M. Elrashied ◽

Alaa I. Mohammed ◽

Sara A. Mirghani ◽

Rania E. Osman ◽

...

Keyword(s):

Diabetes Mellitus ◽

Protein Structure ◽

In Silico Analysis ◽

Structure And Function ◽

Novel Mutations ◽

Inherited Disorders ◽

Bioinformatics Tools ◽

Extrapyramidal Signs ◽

And Function ◽

Silico Analysis

AbstractBackgroundWoodhouse-Sakati Syndrome refers to a group of inherited disorders characterized by alopecia, hypogonadism, diabetes mellitus, hypothyroidism and progressive extrapyramidal signs. The aim of this study is to identify the pathogenic SNPs in theDCAF17gene with their related mciroRNAs and their effect on the structure and function of the protein.Material and MethodsWe used different bioinformatics tools to predict the effect of each SNP on the structure and function of the protein. After that we defined the miRNAs founded in the 3′-UTR region on theDCAF17gene and studied the annotations relative to it.ResultsTen deleterious SNPs out of 339 were found to have a damaging effect on the protein structure and function, with one significant micoRNA in the 3′-UTR region.ConclusionThis was the first in silico analysis ofDCAF17gene, in which 10 novel mutations were found using different bioinformatics tools that could be used as a diagnostic markers for Woodhouse-Sakati syndrome, with one relevant microRNA that can regulate the function of the protein.

Download Full-text

Novel mutations within PRSS1 Gene that could potentially cause hereditary pancreatitis: Using Comprehensive in silico Approach

10.1101/519926 ◽

2019 ◽

Author(s):

Mujahed I. Mustafa ◽

Abdelrahman H. Abdelmoneim ◽

Nafisa M. Elfadol ◽

Soada A. osman ◽

Tebyan A. Abdelhameed ◽

...

Keyword(s):

In Silico ◽

In Silico Analysis ◽

Structure And Function ◽

Incomplete Penetrance ◽

Nucleotide Polymorphisms ◽

Hereditary Pancreatitis ◽

Novel Mutations ◽

Autosomal Dominant Disorder ◽

And Function ◽

Silico Analysis

AbstractBackgroundHereditary pancreatitis (HP) is an autosomal dominant disorder with incomplete penetrance characterized by recurring episodes of severe abdominal pain often presenting in childhood. The comprehensive in silico analysis of coding SNPs, and their functional impacts on protein level, still remains unknown. In this study, we aimed to identify the pathogenic SNPs in PRSS1 gene by computational analysis approach.Materials and MethodsWe carried out in silico analysis of structural effect of each SNP using different bioinformatics tools to predict Single-nucleotide polymorphisms influence on protein structure and function.ResultTwo novel mutations out of 339 nsSNPs that are found be deleterious effect on the PRSS1 structure and function.ConclusionThis is the first in silico analysis in PRSS1 gene, which will be a valuable resource for future targeted mechanistic and population-based studies.

Download Full-text

In Silico Analysis and Modeling of Novel Pathogenic Single Nucleotide Polymorphisms (SNPs) in Human CD40LG Gene

10.1101/552596 ◽

2019 ◽

Cited By ~ 1

Author(s):

Abdelrahman H. Abdelmoneim ◽

Mujahed I. Mustafa ◽

Thwayba A. Mahmoud ◽

Naseem S. Murshed ◽

Mohamed A. Hassan

Keyword(s):

In Silico ◽

Elevated Serum ◽

In Silico Analysis ◽

Structure And Function ◽

Immunoglobulin M ◽

Hyper Igm Syndrome ◽

Bioinformatics Tools ◽

Hyper Igm ◽

And Function ◽

Silico Analysis

Abstract:Background:The X-linked hyper-immunoglobulin M syndrome (XHIGM) is a rare, inherited immune deficiency disorder. It is more common in males. Characterized by elevated serum IgM levels and low to undetectable levels of serum IgG, IgA and IgE. Hyper-IgM syndrome is caused by mutations in the CD40LG gene. Located in human Xq26. CD40LG acts as an immune modulator in activated T cells.Method:We used different bioinformatics tools to predict the effect of each SNP on the structure and function of the protein.Result:8 novel SNPs out of 233 were found to have most deleterious effect on the protein structure and function. While modeling of nsSNPs was studied by Project HOPE software.Conclusion:Better understanding of Hyper-IgM syndrome caused by mutations in CD40LG gene was achieved using in silico analysis. This is the first in silico functional analysis of CD40LG gene and 8 novel mutations were found using different bioinformatics tools, and they could be used as diagnostic markers for hyper-IgM syndrome. These 8 novel SNPs may be important candidates for the cause of different types of human diseases by CD40LG gene.

Download Full-text

Familial Mediterranean Fever

Acta Medica (Hradec Kralove Czech Republic) ◽

10.14712/18059694.2014.47 ◽

2014 ◽

Vol 57 (3) ◽

pp. 97-104 ◽

Cited By ~ 18

Author(s):

Adem Kucuk ◽

Ilknur Albayrak Gezer ◽

Ramazan Ucar ◽

Ali Yavuz Karahan

Keyword(s):

Familial Mediterranean Fever ◽

Clinical Evaluation ◽

Mediterranean Basin ◽

Autosomal Recessive ◽

Mefv Gene ◽

Genetic Mutation ◽

Inherited Disease ◽

Chromosome 16 ◽

Important Complication ◽

Mediterranean Fever

Familial Mediterranean Fever is an autosomal recessive inherited disease with a course of autoinflammation, which is characterized by the episodes of fever and serositis. It affects the populations from Mediterranean basin. Genetic mutation of the disease is on MEFV gene located on short arm of Chromosome 16. The disease is diagnosed based on clinical evaluation. Amyloidosis is the most important complication. The only agent that decreases the development of amyloidosis and the frequency and severity of the episodes is colchicine, which has been used for about 40 years. In this review, we aimed to discuss especially the most recent advances about Familial Mediterranean Fever which is commonly seen in our population.

Download Full-text

Insilico Analysis Reveal Three novel nsSNPs May effect on GM2A protein Leading to AB variant of GM2 gangliosidosis

10.1101/853085 ◽

2019 ◽

Author(s):

Tebyan A. Abdelhameed ◽

Mujahed I. Mustafa ◽

Dina N. Abdelrahman ◽

Fatima A. Abdelrhman ◽

Mohamed A. Hassan

Keyword(s):

Binding Sites ◽

Nucleotide Substitution ◽

Neurodegenerative Disorder ◽

Structure And Function ◽

Gm2 Gangliosidosis ◽

Novel Mutations ◽

Single Nucleotide ◽

Bioinformatics Tools ◽

Gm2 Activator ◽

And Function

ABSTRACTBackgroundAB variant of GM2 gangliosidosis caused as a result of mutations in GM2 activator gene (GM2A) which is regarded as neurodegenerative disorder. This study aimed to predict the possible damaging SNPs of this gene and their impact on the protein using different bioinformatics tools.MethodsSNPs retrieved from the NCBI database were analyzed using several bioinformatics tools. The different tools collectively predicted the effect of single nucleotide substitution on both structure and function of GM2 activator.ResultsThree novel mutations were found to be highly damaging to the structure and function of the GM2A gene.ConclusionFour SNPs were found to be highly damaging SNPs that affect function, structure and stability of GM2A protein, which they are: C99Y, C112F, C138S and C138R, three of them are novel SNPs (C99Y, C112F and C138S). Also 46 SNPs were predicted to affect miRNAs binding sites on 3’UTR leading to abnormal expression of the resulting protein. These SNPs should be considered as important candidates in causing AB variant of GM2 gangliosidosis and may help in diagnosis and genetic screening of the disease.

Download Full-text

E148Q of the MEFV Gene Causes Amyloidosis in Familial Mediterranean Fever Patients

PEDIATRICS ◽

10.1542/peds.108.1.215 ◽

2001 ◽

Vol 108 (1) ◽

pp. 215-215 ◽

Cited By ~ 4

Author(s):

N. Akar ◽

E. Akar ◽

F. Yalcinkaya; ◽

G. J. Halpern ◽

A. Mimouni ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Mefv Gene ◽

Mediterranean Fever

Download Full-text

AB0980 CASE-REVIEW ON FAMILIAL MEDITERRANEAN FEVER IN A SPECIALIZED CENTRE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1355 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1784.1-1784

Author(s):

R. Dos Santos Sobrín ◽

M. Martí Masanet ◽

B. Lopez-Montesinos ◽

L. Lacruz Pérez ◽

I. Calvo

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Familial Mediterranean Fever ◽

Periodic Fever ◽

Severe Disease ◽

Strong Association ◽

Mefv Gene ◽

Systemic Juvenile Idiopathic Arthritis ◽

Case Series ◽

Case Review ◽

Mediterranean Fever

Background:Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disorder caused mostly by mutations in MEFV gene. Its inheritance is autosomal recessive and is the most frequent periodic fever syndrome. First-line treatment is based in colchicine use, so biologics (anti-IL-1) are reserved for refractory cases1, 2.Objectives:To account for clinic and treatment features of patients with FMF in a specialized center as opposed to non-referent centers.Methods:This study was developed in the Pediatric Rheumatology Service in Hospital Universitario y Politécnico La Fe de Valencia. Demographic, clinic and treatment data were collected from patients diagnosed of FMF since January 2004 to September 2019.Results:106 patients met last FMF criteria3. 55% had a pathogenic mutation in genetic analysis. 52% were female. Before 10 years old, 71% of patients had the diagnosis (51% before 4 years old). Arthralgia/myalgia (73%), periodic fever (62%) and abdominal pain (54%) were the most common symptoms. Systemic Juvenile Idiopathic Arthritis (JIA, 6), other forms of JIA (9) and vasculitis (10) were the most prevalent comorbidities. When talking about treatment, 76,4% received Colchicine (60,5% with good response), 22,6% needed a classical disease modifying antirheumatic drug (mostly Methotrexate) and 22 patients got biologic treatment (73% anti-IL-1).Conclusion:When analyzing this case-review, JIA has a strong association with our patients, so it could explain severe disease activity and more articular involvement. This could be an illustration to the higher use of Methotrexate. Also, the most relevant symptom was arthralgia while fever is the most frequent in literature. Likewise, age of diagnosis has been earlier than other case-series (this would be more frequent in other autoinflammatory syndromes, as literature relates)1, 2, 4.References:[1]Ozdogan H, Ugurlu S. Familial Mediterranean Fever. Presse Med. (2019).[2]Ozen S, Demirkaya E, Erer B, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis 2016;75:644-651.[3]Sag E, Demirel D, Demir S, et al. Performance of the new “Eurofever/PRINTO classification criteria” in FMF patients. Semin Arthritis Rheum. 2019;19:30369-5.[4]Rozenbaum M, Rosner I. Severe outcome of juvenile idiopathic arthritis (JIA) associated with familial Mediterranean fever (FMF). Clin Exp Rheumatol. 2004;22:S75-8.Disclosure of Interests:Raquel Dos Santos Sobrín: None declared, Miguel Martí Masanet: None declared, B Lopez-Montesinos: None declared, Lucía Lacruz Pérez: None declared, Inmaculada Calvo Grant/research support from: Bristol-Myers Squibb, Clementia, GlaxoSmithKline, Hoffman-La Roche, Merck Sharpe & Dohme, Novartis, Pfizer, Sanofi, Speakers bureau: AbbVie, GlaxoSmithKline, Hoffman-La Roche, Novartis

Download Full-text