Search

Background: Caring for a child with cystic fibrosis (CF) is challenging and stressful and even more so in a country with limited resources. Our aim was to study the impact of CF on the daily life of mothers with children who have CF in Tunisia, emphasizing the difficulties encountered., Methods: Overall, 20 participants were interviewed about their experiences of being caregivers and mothers of children with CF, including their knowledge about the condition, their attitude toward it, the impact of CF on their daily lives, the main difficulties they had faced, and their concerns and wishes about CF management., Results: The median age of the interviewees was 39 years. None of the mothers had known about CF before; 14 of them had difficulty accepting it at first, with suicidal thoughts in one case. Six hid the illness from the close family for fear of negative prejudices. Three mothers decided to stop having children despite availability of prenatal screening. CF also influenced the mothers' social activities (n = 13) and interfered with their jobs (n = 5). It was responsible for additional expenses in all cases. Chest physiotherapy represented a daily source of coping for all participants. Hospitalization related to Pseudomonas aeruginosa infection was considered stressful and constraining by 12 mothers. The mothers' main concern was the child's life expectancy (n = 7). Their main wish was to administer a curative treatment (n = 17)., Conclusion: CF was found to have deeply affected the mothers' psychosocial life stressing the need for the involvement of qualified psychologists and social workers together with the medical staff., Competing Interests: Declaration of Interest The authors declared no conflict of interest., (Copyright © 2022 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

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.)

Background: Congenital disorders of fibrinogen are rare diseases resulting in the complete absence (afibrinogenemia), reduced concentration (hypofibrinogenemia) or altered function of circulating fibrinogen (dysfibrinogenemia). A combination of two different fibrinogen abnormalities with a significant functional and secretion defect (hypodysfibrinogenemia) reported in Tunisian family members, was investigated in this study., Methods: The coagulation-related tests, kinetics of fibrin polymerization and lysis and fibrinogen analysis using gel electrophoresis were performed in the family members to characterize fibrinogen abnormalities. All exons including exon-intron boundaries of fibrinogen genes were screened by direct sequencing., Results: Mutational screening of the fibrinogen genes disclosed novel missense mutations, BβCys197Arg, in exon 4 of the fibrinogen Bβ-chain gene. After the loose of its partner in Bβ-chain, the γCys135 was probably disulfide-bridged to its corresponding Cys residue of another abnormal fibrinogen molecule, forming dimmer with an abnormal electrophoretic profile. Homozygous form carried by the proband found to be directly involved in the bleeding phenotype by affecting fibrin polymerization. In contrast, affected family members bearing the heterozygous mutation showed an impaired fibrin polymerization and fibrinolysis leading to thrombosis., Conclusion: These results suggest that this mutation could alter the extremely conserved conformations of fibrinogen D domain and D-D lateral regions on fibrin assembly., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A minority of Alzheimer disease (AD) patients begin presenting symptoms before the age of 65 years. A familial aggregation is often found in this group of early-onset AD, and, in a subset of families, the pattern of inheritance is consistent with autosomal dominant inheritance. Fully penetrant variants in amyloid precursor protein, presenilin 1 (PSEN1), and presenilin 2 are the only causative mutations reported for autosomal dominant AD. This study is to explore the PSEN1 gene mutation in a Tunisian familial Alzheimer's disease. The patient in this family showed a novel missense mutation in exon 4 of the PSEN1 gene (complementary DNA 248T>C), altering isoleucine to threonine at 83 position. Because the change occurred in conserved domains of this gene, and cosegregated with affected family member, we suggested that this change may have a mutagenic and probably pathogenic effect., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: In this work, we are interested to study the implication of -509C/T polymorphism, located in the promoter region of TGFB1 (transforming growth factor β1), in the phenotypic variability of CF patients., Patients and Methods: The present study enrolled 111 CF patients and 100 healthy control subjects. The study of the -509C/T polymorphism was performed using PCR-RFLP method., Results: We found that patients carried non-F508del homozygous mutation with TT genotype was associated to lung symptoms (P=0.04). This association was not found in the sub-groups of patients with F508del at homozygous state P=0.145. No association was found between this polymorphism and the variability of digestive, pancreatic and ileus meconial symptoms., Conclusion: On the basis of our results, the -509C/T polymorphism of the TGFB1 gene seems to be a modulator factor of cystic fibrosis., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Purpose: Determining the frequency of M470V polymorphism in cystic fibrosis and healthy cohort in Tunisia to establish the contribution of M470V polymorphism in cystic fibrosis variable presentation and course. Additionally, studying the origin of cystic fibrosis transmembrane conductance regulator gene in Tunisian population and its evolution among populations worldwide., Patients and Methods: The genotyping of M470V marker was realized by PCR-RFLP technique in 34 unrelated patients and 50 healthy subjects., Results: Statistical difference was found in the genotype and allelic distribution between CF and control groups. Exclusive association between F508del allele and M470 allele was noted., Conclusion: This study has contributed to better understanding involvement of the M470V polymorphism in the CF clinical expression in the Tunisian population and has confirmed the utility of this marker in the study of the origin and evolution of the CFTR locus in the human history., (Copyright © 2015. Published by Elsevier SAS.)

Purpose: We present in this study our 10years experience in prenatal diagnosis of cystic fibrosis performed in the Tunisian population., Patients and Methods: Based on family history, 40 Tunisian couples were selected for prenatal diagnosis. Fetal DNA was isolated from amniotic fluid collected by transabdominal amniocentesis or from chronic villi by transcervical chorionic villus sampling. The genetic analysis for cystic fibrosis mutations was performed by denaturant gradient gel electrophoresis and denaturing high-pressure liquid phase chromatography. We performed microsatellites analysis by capillary electrophoresis in order to verify the absence of maternal cell contamination., Results: Thirteen fetuses were affected, 21 were heterozygous carriers and 15 were healthy with two normal alleles of CFTR gene. Ten couples opted for therapeutic abortion. The microsatellites genotyping showed the absence of contamination of the fetal DNA by maternal DNA in 93.75%., Conclusion: Our diagnostic strategy provides rapid and reliable prenatal diagnosis at risk families of cystic fibrosis., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by a deficiency of phenylalanine hydroxylase. To date, more than 530 mutations in the PAH gene have been reported. In Tunisia, this disease seems to be the result of point mutations, few studies have been published about molecular defects of PKU in our country. In this study, we report a novel deletion in exon 6 of two brothers in a Tunisian family after DHPLC analysis and sequencing of the exon 6 of the PAH gene., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Fluoroquinolones are increasingly used for the treatment of infections caused by multidrug-resistant Mycobacterium tuberculosis. Our study was designed to determine the frequency of the emergence of ciprofloxacin-resistant isolates in a university hospital (Rabta University Hospital Tunis, Tunisia) and to characterize the mutations responsible for the resistance phenotype. A total of 495 clinical M. tuberculosis isolates obtained from January 2005 to July 2008 were investigated for their susceptibility to ciprofloxacin, using the standard proportion method, PCR and DNA sequencing. Four resistant isolates (0.8%) were identified. Among these, only two carried point mutations in gyrA leading to amino acid changes other than the phenotypically silent S95T substitution. No gyrB missense mutations were found in any of the clinical isolates. Although fluoroquinolone resistance is still rare in Tunisia, accurate surveillance is needed in order to control the possible emergence of resistance to fluoroquinolones, which are essential for the successful treatment of multidrug-resistant tuberculosis., (© 2010 The Authors. Journal Compilation © 2010 European Society of Clinical Microbiology and Infectious Diseases.)