Search

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background: Leber hereditary optic neuropathy (LHON) is a mitochondrial DNA (mtDNA) rare disease due to the pathogenic variant of the NADH dehydrogenase enzyme. LHON is characterized by a sudden central vision loss due to focal degeneration of the retinal ganglion cell layer and optic nerve. Symptoms usually appear between the age of 18 and 35 years. Some individuals present the mtDNA mutations but not presented the LHON clinical features. The heteroplasmic or homoplasmic character of the mutations among patients explains why they develop the disease or not even though they carry the pathogenic variant., Methods: This study was performed in collaboration with the department of ophthalmology of Farhat Hached Hospital, Sousse, Tunisia. Screening for the common mutations in Mt-ND1 gene (m.3460G > A), Mt-ND4 gene (m.11778G > A) and Mt-ND6 gene (m.14484T > C) was performed in five Tunisian families by standard RFLP PCR, followed by direct sequencing of the entire of these genes. Indeed, bioinformatics tools were used to predict the potential functional impact of the identified mutations on the Human mitochondrial respiratory complex I protein., Results: one novel p.L601M (m.1413 C > A) and four previously reported mutations were identified in this study including: rs199476112G > A (m.11778G > A); rs202227543G > A (m.14258G > A); rs1603224763 (m.14510 dup) and NC_012920.1: m.3244G > C. In this present report, only one patient was found carrying the primary point mutation (m. 11778G > A). The ophthalmologic findings showing major fundus changes included hyperemic optic discs; disc pseudo-oedema and microangiopathy leading to optic disc atrophy. The analyses of the stability of protein upon identified mutations using DynaMut tool server demonstrated that these variations induce a rigidification in the region where they are located., Conclusion: This is the first Tunisian report of mtDNA mutations identified in Tunisia causing the LHON. The main factors involved in the pathophysiological mechanisms of this disease are genetic, epigenetic, hormonal and environmental influences., Competing Interests: Declarations. Ethics approval and consent to participate: The families gave informed consent before withdrawal of blood samples and written informed consent was obtained and signed by all parents of the studied patients, in addition the verbal consent was also obtained during consultation. The study was approved by the ethics committees for scientific research of the Farhat Hached Hospital Sousse, Tunisia; no reference number was issued. All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 and approved by the Ethics Committees of the respective Tunisian hospitals. Consent to publish: Written informed consent for publication of their clinical details and/or clinical images was obtained from the parents. Copies of the consent forms are available for review by the Editor of this journal. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Mucopolysaccharidosis type I is a lysosomal storage disease resulting from a deficiency in alpha-L-iduronidase (IDUA), which causes the accumulation of partially degraded dermatan sulfate and heparan sulfate. This retrospective study, spanning eight years, analyzed data from 45 MPSI patients. The report aimed to explore the potential origin of the p.P533R mutation in the Maghrebin population by constructing a single-nucleotide polymorphism haplotype around the IDUA gene, in order to propose a molecular proof of a founder effect of the MPSI/p.P533R allele., Patients and Methods: All of the studied patients were from Libya (2), Mauritania (1) Morocco (21) and Tunisia (21) with first cousins being the most frequent union. The diagnosis of MPSI patients often involves the combination of urinary screening, leukocyte IDUA activity determination, and DNA molecular analysis. In our study, to identify the common p.P533R mutation, we performed both DNA sequencing and tetra-primer ARMS PCR assay. Additionally, Haploview was used to determine the specific haplotype that cosegregates with the p.P533R mutation. Controls were genotyped to ensure that all the SNPs were in Hardy-Weinberg equilibrium., Results: In the present report we confirmed the very strong impact of consanguinity on the incidence of MPSI disease. Furthermore, studied families of mixed ancestry shared common and specific haplotype, which was observed in studied populations, suggesting the presence of a founder effect in the North Africa., Conclusion: The p.P533R missense mutation was identified in each patient originated from Libya, Mauritania, Morocco and Tunisia. Furthermore, these MPSI patients exhibited the same IDUA haplotype. The occurrence of a shared AAGGGTG haplotype, among North African populations may be attributed to substantial historical gene exchange between these groups, likely stemming from migration, inter-ethnic marriage, or other forms of interaction throughout history., (© 2024. The Author(s).)

The objective of this study is to take the initial steps toward developing novel antibiotics to counteract the escalating problem of antimicrobial and bacterial persistence, particularly in relation to biofilms. Our approach involves emulating the structural characteristics of cationic antimicrobial peptides. To circumvent resistance development, we have designed a library of bis-benzimidazolium salts that selectively target the microbial membranes in a nonspecific manner. To explore their structure-activity relationship, we conducted experiments using these compounds on various pathogens known for their resistance to conventional antibiotics, including Gram-positive methicillin - resistant Staphylococcus aureus ( MRSA ), vancomycin - resistant Enterococcus faecium ( VRE ), and Gram-negative Escherichia coli ( E. coli ). Notably, two bis-benzimidazolium salts exhibited robust antimicrobial activity while maintaining a high level of selectivity compared with mammalian cells. Our investigations revealed significant antibiofilm activity, as these compounds rapidly acted against established biofilms. In addition, bis-benzimidazolium compounds exhibited consistent results in resistance development and cross-resistance studies. Consequently, amphiphilic bis-benzimidazolium salts hold promise as potential candidates to combat resistance-associated infections.

Background: Glycogen storage disease type 1b (GSD1b) is an autosomal recessive lysosomal storage disease caused by defective glucose-6-phosphate transporter encoded by SLC37A4 leading to the accumulation of glycogen in various tissues. The high rate of consanguineous marriages in Tunisian population provides an ideal environment to facilitate the identification of homozygous pathogenic mutations. We aimed to determine the clinical and genetic profiles of patients with GSD1b to evaluate SLC37A4 mutations spectrum in Tunisian patients., Methods: All exons and flanking intron regions of SLC37A4 gene were screened by direct sequencing to identify mutations and polymorphisms in three unrelated families with GSD1b. Bioinformatics tools were then used to predict the impacts of identified mutations on the structure and function of protein in order to propose a function-structure relationship of the G6PT1 protein., Results: Three patients (MT, MB and SI) in Families I, II and III who had the severe phenotype were homoallelic for the two identified mutations: p.R300H (famillies I, II) and p.W393X (Family III), respectively. One of the alterations was a missense mutation p.R300H of exon 6 in SLC37A4 gene. The analysis of the protein structure flexibility upon p.R300H mutation using DynaMut tool and CABS-flex 2.0 server showed that the reported mutation increase the molecule flexibility of in the cytosol region and would probably lead to significant conformational changes., Conclusion: This is the first Tunisian report of SLC37A4 mutations identified in Tunisia causing the glycogenosis type Ib disease. Bioinformatics analysis allowed us to establish an approximate structure-function relationship for the G6PT1 protein, thereby providing better genotype/phenotype correlation knowledge., (© 2023. The Author(s).)

Background: Hemoglobinopathies, inherited disorders of hemoglobin (Hb), are the most common hereditary monogenic diseases of the red cell in the world. Few studies have been conducted on hemoglobinopathies in Mauritania. Therefore, the aim of this work is to establish the molecular and epidemiological basis of hemoglobinopathies in a cohort of Mauritanian patients and to determine the haplotype of the β-globin gene cluster in sickle cell subjects., Methods: The molecular screening of Hb disorders in 40 Mauritanian patients was done by a polymerase-restriction fragment length polymorphism (RFLP) for the sickle cell disease (SCD) mutation, a PCR/sequencing method for β-thalassemia mutations, and by the multiplex polymerase chain reaction method for the α-thalassemia. The exploration of eight polymorphic sites (SNPs) within the β-globin gene cluster was conducted by PCR/RFLP method, to identify the HbS haplotypes from the sickle cell subjects., Results: The epidemiological study of our patients showed a high incidence in the Senegal River area (52.5%) and a high ethnic prevalence for the Heratin (47.5%) and the Pular (35%). Molecular study allowed us to identify eight different mutations in our sample analyzed. They are respectively: HbS (HBB:c.20A>T) (68.75%), Cd44 -C (HBB:c.135delC) (8.75%), -29A>G (HBB:c.-79A>G) (4.8%), -α-3.7 (g.34164_37967del3804) (3.75%), IVS-II-849A>G (HBB:c.316-2A>G) (2.25%) and Cd24T>A (HBB:c.75T>A), Hb Siirt (HBB:c.83C>G) and HbC (HBB:c.19G>A) each with (1.25%). Six different haplotypes are being explored among the SCD subjects with the Senegal haplotype as the most prevalent (66.7%), followed by Benin (10%), Arab-Indians (6.7%), Bantu (3.3%), and two atypical haplotypes., Conclusion: Our findings enrich the epidemiological data in our population and could contribute to the establishment of a strategy of prevention and management through screening, genetic counseling, and prenatal diagnosis of Hemoglobinopathies in the Mauritanian population., (© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Microorganisms grouped together into spatially-organized communities called biofilms, are the cause of dramatic chronic infections in plants, animals and humans. In this review, the characteristics of biofilms and their interactions with antimicrobials are first described. Limitations of antibiotic treatments are discussed, and state-of-the-art alternative approaches based on the use of polymer, lipid, organic, inorganic and hybrid nanoparticles are presented, highlighting recent achievements in the application of nanomaterials to the field of theranostics for the eradication of biofilm. The aim of this review is to present a complete vision of nanobiotechnology-based approaches for eradicating bacterial biofilms and fighting antimicrobial tolerance., Competing Interests: Competing Interests: The authors declare no competing financial interest., (© The author(s).)

Background and Objectives: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy worldwide associated with hemolysis as well as neonatal jaundice, kernicterus, and even death. The goal of this study is to determinate the prevalence of G6PD deficiency in icteric neonates and to investigate its biochemical, hematological and molecular characteristics., Patients and Methods: This cross sectional study was carried out on 154 icteric newborns admitted to the Bechir Hamza Children's Hospital in Tunisia. Laboratory evaluations included complete blood count, total serum bilirubin level (TSB), and erythrocyte G6PD activity. The G6PD activity was determined using a quantitative assay, which allowed us to divide the total population into two groups: normal and deficient population. The common G6PD Tunisian mutations (GdA - and GdMed) were determined using the amplification refractory mutation system (ARMS-PCR) method., Results: The prevalence of G6PD deficiency among total population (154 icteric newborns) was 18.83%. Male neonates showed a higher incidence of G6PD deficiency of 11.03% compared to females (7.79%). There was no statistical difference between the two groups (normal and deficient), in relation to the sex, peak TSB level, age at peak TSB, hemoglobin level, and hematocrit. However, there was a significant difference in gestational age. In the deficient group, 48.28% neonates presented the peak TSB level between 3 to 7 days and 55% of the cases show a peak TSB level greater than 250 μmol/L. The G6PD G202A variant was found in 41.37% of cases., Conclusion: This study shows a higher prevalence of G6PD deficiency in icteric newborns of Tunisia (18.83%). This emphasizes the necessity of neonatal screening for G6PD deficiency to prevent the exposure of these newborns to known hemolytic agents and, subsequently, to prevent kernicterus or other serious complications.

Congenital atransferrinemia is an extremely rare autosomal recessive disorder resulting in the complete absence or extremely reduced amount of transferrin. In this study, we describe the first case of congenital atransferrinemia in Tunisia and the 18th patient in the reported data. The patient was referred to our hospital to explore a severe hypochromic and microcytic anemia. The laboratory evaluation including hematological and biochemical examination was performed in the proband and her parents. All exons of the transferrin gene were PCR amplified. The products were screened for mutations by direct sequencing. Based on laboratory and clinical findings, diagnosis of congenital atransferrinemia was confirmed. DNA sequencing revealed the presence of a novel homozygous deletion (c.293-63del) in the intron 13. This mutation is predicted to generate a higher score cryptic branch point leading to the production of an altered mRNA molecule. The second previously reported missense mutation p.Arg609Trp. Crystallographic structure analyzes demonstrate that the mutation would probably lead to significant conformational change not allowing the expression of transferrin protein. Current molecular characterization of this novel transferrin abnormality puts to the proof the variability in onset, first blood transfusion, and phenotypic expression in atransferrinemic patients., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Switzerland has a high rate of legal measures of constraint by international standard. Beside the incorporation of legal, medical and economic elements, the physician may be asked on what it means to be a care giver and to be free, because his decision could private his patient of a fundamental human right. The deprivation of freedom for purposes of assistance is helpful in some clinical situations but remains a controversial issue. We have to do our due diligence when assessing the patient, notably his capacity of discernment, and discuss with him and his relatives other treatments without legal constraint. The advance directives and the joint plan of crisis should be tools to increase patients' autonomy and to decrease the coercive measures., Competing Interests: L’auteur n’a déclaré aucun conflit d’intérêts en relation avec cet article.

HbA 1c is used for monitoring diabetic balance. In this paper we report an assessment of the analytical performances of Capillarys 2 Flex Piercing (C2FP) for HbA 1c measurement using CE (Capillary Electrophoresis). CLSI (Clinical and Laboratory Standard Institute) protocols are used for the evaluation of apparatus performances: precision, linearity, method comparison, trueness and common interferences. HbA 1c CVs average in intra-assay was 1.6% between run imprecision CV ranged from 0.1 to 1.8%. The linearity was demonstrated between 4.7 and 15.0%. The comparison study revealed that Bland Altman plot mean difference was equal to -0.03 (CI 95% (-0.05 to -0.0003)) and Passing-Bablok regression intercept was -0.05, CI95%(-0.13 -  -0.05); slope: 1.00, CI95%[1.00-1.01]. A strong correlation (r > 0.99) was proved. No significant effects of hemoglobin variants were seen with CE on HbA 1c measurement. No problem related to sample-to-sample carry over was noted. No interferences of LA 1c and cHb were observed. CE allowed quantification of HbA 1c even at low level of total hemoglobin (40 g/L) in contrast to HPLC. Furthermore, this analyzer offered the opportunity of quantifying the HbA 2 simultaneously with HbA 1c . This evaluation showed that C2FP is a convenient system for the control of diabetes and the detection of hemoglobinopathies., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: In this work, we are interested to study for the first time the extragenic polymorphic marker MP6d9 in cystic fibrosis and healthy cohort in Tunisia to establish the contribution of MP6d9 polymorphism in the phenotypic variability of CF patients., Methods: Our study enrolled 112 CF patients and 100 healthy controls. The analysis of the polymorphic marker MP6d9 was performed using the PCR-RFLP technique., Results: Statistical difference was found in the genotype and allelic distribution between CF patients and control groups. We found that the 2/2 genotype was higher in CF patients than in controls (58.9% vs 23%). We noted that the 2/2 genotype is associated with severe clinical manifestations., Conclusion: Based on the above data, it seems that this genotype has led to the deterioration of our patient's clinical manifestation. This study enabled us to understanding the involvement of the MP6d9 marker in the CF clinical expression in the Tunisian population.