Distribution of MEFV gene mutations and R202Q polymorphism in the Serbian population and their influence on oxidative stress and clinical manifestations of inflammation

Background and Aims: Familial mediterranean fever (FMF), an autoinflammatory disease, is characterized by periodic fever and serositis. An MEFV gene mutation has been identified as the cause of FMF. Recently, patients with MEFV gene mutations and chronic gastrointestinal mucosal inflammation mimicking inflammatory bowel disease (IBD) have been reported. In this retrospective study, we analyzed the clinical characteristics of patients with IBD unclassified (IBDU) with MEFV gene mutations. Methods: MEFV gene analysis was performed on 8 patients with IBDU among 710 patients with IBD who had been treated at Kyorin University Hospital from April 2016 to December 2018. Clinical manifestations, endoscopic findings, and serological markers were also analyzed. Results: The average of the 8 patients with IBDU (3 men, 5 women) was 32.7 ± 6.4 years (range 26–76 years). Their symptoms comprised diarrhea (n = 8, 100%), hematochezia (n = 3, 37.5%), abdominal pain (n = 3, 37.5%), high fever (n = 2, 16.5%), and other periodic symptoms (n = 2, 16.5%). MEFV gene mutation was confirmed in 4/8 of these patients. Colonoscopy showed various mucosal lesions, rectal sparing, right side dominant colitis, pseudopolyposis, and granular protrusions. Colchicine was administered to 5 of the 8 patients (4 with and 1 without MEFV mutation) who were resistant to conventional treatment for ulcerative colitis. Clinical and endoscopic improvement was observed in all of 5 patients treated with colchicine. Conclusions: Some patients diagnosed as having IBDU have enterocolitis related to MEFV gene mutation and respond to colchicine therapy.

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Idiopathic CRMO and MEFV Gene Variant Alleles: Is There Any Relationship?

Case Reports in Rheumatology ◽

10.1155/2019/9847867 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4

Author(s):

Farhad Salehzadeh ◽

Hassan Anari ◽

Sepehr Sarkhanloo

Keyword(s):

Age Of Onset ◽

Mefv Gene ◽

Clinical Manifestations ◽

Gene Mutations ◽

Bone Lesions ◽

Gene Variant ◽

Intermittent Fever ◽

Pathogenic Variants ◽

Long Duration ◽

Variant Alleles

Background and Objective. CRMO is an inflammatory disease of bone that occurs more often in children. The clinical manifestations are intermittent fever, pain, and bone lesions, especially in long bones. Although there is an idiopathic type of disease, it is usually associated with some autoimmune disorders. This study evaluates MEFV gene mutations as background pathology of idiopathic CRMO. Methods. Blood samples of patients, who diagnosed as childhood idiopathic CRMO by imaging and pathologic study from June 2011 until September 2018, have been screened for the 12 common pathogenic variants of MEFV gene mutations. Result. Nine patients enrolled in this study, and eight of them were male. The most common involvement locations were tibia and femur, and the least ones were zygoma, calcaneus, and radius. The mean duration of the involvement was 1.3 years. Six patients had only 1 involved location, 2 patients showed two sites of involvement, and one patient had three affected areas. There were two positive MEFV gene mutations (22%), as E148Q/wt and K695R/wt both in the heterozygote form. There was no meaningful relationship between MEFV gene mutations and the age of onset, gender, and location of involvement. Patients with positive mutation had more involved sites and long duration of involvement significantly. Conclusion. There is no significant immunopathogenic relationship between the common MEFV gene variant alleles and CRMO disease.

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Novel missense mutation of SASH1 in a Chinese family with dyschromatosis universalis hereditaria

BMC Medical Genomics ◽

10.1186/s12920-021-01014-w ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Lu Cao ◽

Ruixue Zhang ◽

Liang Yong ◽

Shirui Chen ◽

Hui Zhang ◽

...

Keyword(s):

Missense Mutation ◽

Sequence Alignment ◽

Multiple Sequence Alignment ◽

Molecular Genetic ◽

Family Members ◽

Clinical Manifestations ◽

Gene Mutations ◽

Mendelian Inheritance ◽

Chinese Family ◽

Multiple Sequence

Abstract Background Dyschromatosis universalis hereditaria (DUH) is a pigmentary dermatosis characterized by generalized mottled macules with hypopigmention and hyperpigmention. ABCB6 and SASH1 are recently reported pathogenic genes related to DUH, and the aim of this study was to identify the causative mutations in a Chinese family with DUH. Methods Sanger sequencing was performed to investigate the clinical manifestation and molecular genetic basis of these familial cases of DUH, bioinformatics tools and multiple sequence alignment were used to analyse the pathogenicity of mutations. Results A novel missense mutation, c.1529G>A, in the SASH1 gene was identified, and this mutation was not found in the National Center for Biotechnology Information Database of Short Genetic Variation, Online Mendelian Inheritance in Man, ClinVar, or 1000 Genomes Project databases. All in silico predictors suggested that the observed substitution mutation was deleterious. Furthermore, multiple sequence alignment of SASH1 revealed that the p.S510N mutation was highly conserved during evolution. In addition, we reviewed the previously reported DUH-related gene mutations in SASH1 and ABCB6. Conclusion Although the affected family members had identical mutations, differences in the clinical manifestations of these family members were observed, which reveals the complexity of the phenotype-influencing factors in DUH. Our findings reveal the mutation responsible for DUH in this family and broaden the mutational spectrum of the SASH1 gene.

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Prevalence and clinical phenotype of the triplicated α-globin genes and its ethnic and geographical distribution in Guizhou of China

BMC Medical Genomics ◽

10.1186/s12920-021-00944-9 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Xi Luo ◽

Xiang-mei Zhang ◽

Liu-song Wu ◽

Jindong Chen ◽

Yan Chen

Keyword(s):

Genetic Counseling ◽

Peripheral Blood ◽

Clinical Phenotype ◽

Globin Gene ◽

Clinical Manifestations ◽

Gene Mutations ◽

Guizhou Province ◽

Globin Genes ◽

Phenotype Correlation ◽

Chi Square

Abstract Background α-thalassemia is relatively endemic in Guizhou province of southwestern China. To predict the clinical manifestations of α-globin gene aberration for genetic counseling, we examined the prevalence of the α-globin triplication and the genotype–phenotype correlation in this subpopulation Methods A cohort of 7644 subjects was selected from nine ethnicities covering four regions in Guizhou province of China. Peripheral blood was collected from each participant for routine blood testing and hemoglobin electrophoresis. PCR-DNA sequencing and Gap-PCR were used to identify the thalassemia gene mutations. Chi-square tests and one-way analysis of variance (ANOVA) were used to statistically analyze the data. Results We found that the frequency of α-globin triplication in Guizhou province was 0.772% (59/7644). Genotypically, the αααanti4.2/αα accounted for 0.523% (40/7644), the αααanti3.7/αα for 0.235% (18/7644), and the αααanti3.7/–SEA for 0.013% (1/7644). The αααanti4.2/αα is more prevalent than the αααanti3.7/αα in Guizhou. In addition, the frequency of the HKαα/αα (that by GAP-PCR is like αααanti4.2/-α3.7) was 0.235% (18/7644). Ethnically, the Tujia group presented the highest prevalence (2.47%) of α-globin triplication. Geographically, the highest frequency of the α-globin triplication was identified in Qiannan region (2.23%). Of the triplicated α-globin cases, 5 coinherited with heterozygote β-thalassemia and presented various clinical manifestations of anemia. Conclusions These data will be used to update the Chinese triplicated α-globin thalassemia database and provide insights into the pathogenesis of thalassemia. These findings will be helpful for the diagnosis of thalassemia and future genetic counseling in those regions.

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Prevalence of MEFV gene mutations and their clinical correlations in Turkish children with Henoch-Schönlein purpura

Acta Paediatrica ◽

10.1111/j.1651-2227.2011.02143.x ◽

2011 ◽

Vol 100 (5) ◽

pp. 745-749 ◽

Cited By ~ 22

Author(s):

Cengiz Bayram ◽

Gülay Demircin ◽

Özlem Erdoğan ◽

Mehmet Bülbül ◽

Aysun Çaltık ◽

...

Keyword(s):

Mefv Gene ◽

Gene Mutations ◽

Henoch Schonlein Purpura ◽

Turkish Children ◽

Clinical Correlations ◽

Schonlein Purpura ◽

Henoch Schönlein Purpura

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Comprehensive Analysis of a Large-Scale Screen for MEFV Gene Mutations: Do They Truly Provide a “Heterozygote Advantage” in Turkey?

Genetic Testing and Molecular Biomarkers ◽

10.1089/gtmb.2010.0146 ◽

2011 ◽

Vol 15 (7-8) ◽

pp. 475-482 ◽

Cited By ~ 5

Author(s):

Afig Berdeli ◽

Sevgi Mir ◽

Sinem Nalbantoglu ◽

Necil Kutukculer ◽

Betül Sozeri ◽

...

Keyword(s):

Large Scale ◽

Mefv Gene ◽

Gene Mutations ◽

Comprehensive Analysis ◽

Heterozygote Advantage

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MEFV gene mutations in Iranian patients with familial mediterranean fever (FMF)

The American Journal of Gastroenterology ◽

10.1016/s0002-9270(03)00980-8 ◽

2003 ◽

Vol 98 (9) ◽

pp. S72-S73 ◽

Cited By ~ 1

Author(s):

M ZALI

Keyword(s):

Familial Mediterranean Fever ◽

Mefv Gene ◽

Gene Mutations ◽

Mediterranean Fever ◽

Iranian Patients

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Common Mediterranean Fever (MEFV) Gene Mutations Associated with Ankylosing Spondylitis in Turkish Population

Disease Markers ◽

10.1155/2012/890214 ◽

2012 ◽

Vol 33 (3) ◽

pp. 113-118 ◽

Cited By ~ 9

Author(s):

Serbulent Yigit ◽

Ahmet Inanir ◽

Nevin Karakus ◽

Esra Kesici ◽

Nihan Bozkurt

Keyword(s):

Ankylosing Spondylitis ◽

Mefv Gene ◽

Gene Mutations ◽

Turkish Population ◽

M694v Mutation ◽

Significant Difference ◽

Mediterranean Fever ◽

Genomic Dnas ◽

Polymerase Chain ◽

Turkish Patients

Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease. Mediterranean fever (MEFV) gene, which has already been identified as being responsible for familial Mediterranean fever (FMF), is also a suspicious gene for AS because of the clinical association of these two diseases. The aim of this study was to explore the frequency and clinical significance ofMEFVgene mutations (M694V, M680I, V726A, E148Q and P369S) in a cohort of Turkish patients with AS. Genomic DNAs of 103 AS patients and 120 controls were isolated and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. There was a statistically significant difference of theMEFVgene mutation carrier rates between AS patients and healthy controls (p= 0.004, OR: 2.5, 95% CI: 1.32–4.76). This association was also observed in allele frequencies (p= 0.005, OR: 2.3, 95% CI: 1.27–4.2). A relatively higher frequency was observed for M694V mutation in AS patients than controls (10.7% versus 4.2% ,p= 0.060). There were no significant differences between MEFV mutation carriers and non-carriers with respect to the clinical and demographic characteristics. The results of this study suggest thatMEFVgene mutations are positively associated with a predisposition to develop AS.

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Role of antioxidant therapy in patients with moderate and severe COVID-19

Infekcionnye bolezni ◽

10.20953/1729-9225-2021-1-159-164 ◽

2021 ◽

Vol 19 (1) ◽

pp. 159-164

Author(s):

E.K. Shavarova ◽

◽

E.R. Cazakhmedov ◽

M.V. Alekseeva ◽

L.G. Ezhova ◽

...

Keyword(s):

Oxidative Stress ◽

Intervention Group ◽

Clinical Manifestations ◽

Organ Damage ◽

Control Group ◽

Reactive Protein ◽

Virus Rna ◽

Active Intervention Group ◽

Group 2 ◽

Novel Coronavirus

The coronavirus disease COVID-19 is characterized by high mortality and the lack of effective etiotropic therapy. Activation of oxidative stress may be one of the links in the pathogenesis of organ damage of this infection. Objective. To assess the ability of Mexidol® to influence the rate of clinical improvement in pneumonia caused by the SARSCoV-2 virus in hospitalized patients with the novel coronavirus disease COVID-19 and concomitant discirculatory encephalopathy. 62 patients over the age of 18 years with confirmed new coronavirus disease COVID-19 according to computed tomography (CT) of the lungs (stages CT1, CT2, CT3) and PCR of a swab from the nasopharynx and oropharynx for SARS-CoV-2 virus RNA were included. After randomization patients of group 1 received an infusion of Mexidol® at a dose of 1000 mg/day, patients of group 2 – an infusion of isotonic sodium chloride solution for 7 days. Compared with the control group, the patients receiving Mexidol® therapy showed a significantly more pronounced decrease in body temperature, a tendency towards a decrease in the severity of shortness of breath. In the Mexidol® group, the concentration of superoxidedismutase did not change, while in the control group there was a tendency to its decrease, C-reactive protein decreased 2.2 times more than in the control group (p = 0.09). There was a tendency for a more rapid decrease in ferritin in the active intervention group. Mexidol® therapy can have a positive effect on the clinical manifestations and severity of laboratory-inflammatory syndrome in patients with the new coronavirus disease COVID-19. Key words: coronavirus disease COVID-19, oxidative stress, Mexidol

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