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Gardner syndrome (GS) is a subtype of familial adenomatous polyposis (FAP) characterized by colorectal polyps, multiple osteomas, soft tissue tumors, and specific oral manifestations, such as jaw osteomas. GS is caused by mutations in the APC gene, resulting in a nonfunctional protein. This study reports a comprehensive clinical evaluation and genetic analysis of a Tunisian family affected by GS. Targeted exome sequencing and Sanger sequencing techniques were employed to identify and validate mutations in the APC gene. Clinical observations of the patient revealed multiple sebaceous cysts, frontal and maxillary osteomas, and several gastrointestinal polyps. Genetic analysis revealed a pathogenic variant (c.4652-4655del) in the APC gene, leading to a truncated protein. Additionally, genetic testing of the patient's child indicated that the child does not carry the APC pathogenic variant. In conclusion, our study highlights the importance of genetic testing in raising awareness of GS among clinicians to ensure early diagnosis and effective management, thereby reducing the risk of development and progression of colorectal cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Constitutional Mismatch Repair Deficiency (CMMRD) is a rare childhood cancer predisposition syndrome, caused by biallelic pathogenic germline variants in the mismatch repair genes. Diagnosis and management of this syndrome is challenging, especially in low-resource settings. This study describes a patient diagnosed with colorectal cancer and grade 3 astrocytoma at the age of 11 and 12 respectively. Immunohistochemistry analysis showed a loss of MSH2 and MSH6 protein expression in CRC tissues of the patient. We identified by Targeted Exome Sequencing a homozygous pathogenic germline variant in exon 9 of the MSH6 gene (c.3991 C > T; p.Ala1268Glyfs*6). Genetic investigation of the family showed that the father was heterozygous for the identified pathogenic variant while the brother was wild type for this variant. Our study highlights the importance of a correct and timely diagnosis of CMMRD which can have implications for treatment. It also underlines the imperative need to enhance awareness, diagnostic standards, and surveillance that are crucial for patients and their families., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Key discoveries and innovations in the field of human genetics have led to the foundation of molecular and personalized medicine. Here, we present the Genome Tunisia Project, a two-phased initiative (2022-2035) which aims to deliver the reference sequence of the Tunisian Genome and to support the implementation of personalized medicine in Tunisia, a North African country that represents a central hub of population admixture and human migration between African, European, and Asian populations. The main goal of this initiative is to develop a healthcare system capable of incorporating omics data for use in routine medical practice, enabling medical doctors to better prevent, diagnose, and treat patients., Methods: A multidisciplinary partnership involving Tunisian experts from different institutions has come to discern all requirements that would be of high priority to fulfill the project's goals. One of the most urgent priorities is to determine the reference sequence of the Tunisian Genome. In addition, extensive situation analysis and revision of the education programs, community awareness, appropriate infrastructure including sequencing platforms and biobanking, as well as ethical and regulatory frameworks, have been undertaken towards building sufficient capacity to integrate personalized medicine into the Tunisian healthcare system., Results: In the framework of this project, an ecosystem with all engaged stakeholders has been implemented including healthcare providers, clinicians, researchers, pharmacists, bioinformaticians, industry, policymakers, and advocacy groups. This initiative will also help to reinforce research and innovation capacities in the field of genomics and to strengthen discoverability in the health sector., Conclusions: Genome Tunisia is the first initiative in North Africa that seeks to demonstrate the major impact that can be achieved by Human Genome Projects in low- and middle-income countries to strengthen research and to improve disease management and treatment outcomes, thereby reducing the social and economic burden on healthcare systems. Sharing this experience within the African scientific community is a chance to turn a major challenge into an opportunity for dissemination and outreach. Additional efforts are now being made to advance personalized medicine in patient care by educating consumers and providers, accelerating research and innovation, and supporting necessary changes in policy and regulation., (© 2024. The Author(s).)

Background: Intellectual disability is a form of neurodevelopmental disorders that begin in childhood and is characterized by substantial intellectual difficulties as well as difficulties in conceptual, social, and practical areas of living. Several genetic and nongenetic factors contribute to its development; however, its most severe forms are generally attributed to single-gene defects. High-throughput technologies and data sharing contributed to the diagnosis of hundreds of single-gene intellectual disability subtypes., Method: We applied exome sequencing to identify potential variants causing syndromic intellectual disability in six Sudanese patients from four unrelated families. Data sharing through the Varsome portal corroborated the diagnosis of one of these patients and a Tunisian patient investigated through exome sequencing. Sanger sequencing validated the identified variants and their segregation with the phenotypes in the five studied families., Result: We identified three pathogenic/likely pathogenic variants in CCDC82, ADAT3, and HUWE1 and variants of uncertain significance in HERC2 and ATP2B3. The patients with the CCDC82 variants had microcephaly and spasticity, two signs absent in the two previously reported families with CCDC82-related intellectual disability., Conclusion: In conclusion, we report new patients with pathogenic mutations in the genes CCDC82, ADAT3, and HUWE1. We also highlight the possibility of extending the CCDC82-linked phenotype to include spastic paraplegia and microcephaly., (© 2022 John Wiley & Sons Ltd/University College London.)

A high prevalence of genetic kidney disease in Tunisia has been detected, and their study provides very important clinical and genetic information. Autosomal dominant polycystic kidney disease (ADPKD) is one of the main causes of morbidity and mortality associated with the kidneys in Tunisia. We present here clinical and genetic characteristics of a cohort of Tunisian patients with ADPKD. Nineteen Tunisian patients with ADPKD, among 4 familial cases and 11 sporadic cases, and 50 Healthy individuals were included in this cohort. Genetic studies of PKD1/2 were carried on using Sanger sequencing and MLPA. In our study, the mean age at diagnosis was 47 ± 18 years. In addition, 84.21% of cases present a family history of ADPKD. Overall, 57.89% of the affected individuals had HTA and 26.31% patients had hematuria. 15.78 % of the patient has extra-renal cysts i.e. one patient with splenic cysts and two patients had liver cysts. 57.89 % of patients were diagnosed with various extra-renal clinical presentations i.e. myopia, hernia, deafness, intracranial aneurysm, respiratory distress, hyperthyroidism, urinary tract infection and lower back pains. The PKD1 genotype showed earlier onset of ESRD compared to PKD2 genotype (43 vs. 55 years old). Six mutations have been detected in PKD1 gene. Among them, three were novels e.g. c.688 T>G, p.C230G and c.690C>G, p.C230W among exon 5 and c.8522A>G, p.N2841S among exon 23. In addition, thirteen single nucleotides polymorphisms have been reported in PKD1 gene. Among them, eleven previously reported in heterozygous state and two novel single nucleotides polymorphisms in heterozygous and homozygous state and predicted to be probable polymorphisms by computational tools: c.496C>T, p.L166= among the exon 4, and c.10165G>C and p.E3389Gln among the exon 31. Only three single nucleotides polymorphisms previously reported in ADPKD database have been identified in PKD2 gene. The description and analysis of our cohort can help in rapid and reliable diagnosis for early management of patients in Tunisia. Indeed, predictive genetic testing can facilitate donor evaluation and increase living related kidney transplantation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Intellectual disability (ID) often co-occurs with other neurologic phenotypes making molecular diagnosis more challenging particularly in consanguineous populations with the co-segregation of more than one ID-related gene in some cases. In this study, we investigated the phenotype of three patients from a large Tunisian family with significant ID phenotypic variability and microcephaly and performed a clinical exome sequencing in two cases. We identified, within the first branch, a homozygous variant in the TRAPPC9 gene (p.Arg472Ter) in two cases presenting severe ID, absent speech, congenital/secondary microcephaly in addition to autistic features, supporting the implication of TRAPPC9 in the "secondary" autism spectrum disorders and congenital microcephaly. In the second branch, we identified a homozygous variant (p.Lys189ArgfsTer15) in the CDK5RAP2 gene associated with an heterozygous TRAPPC9 variant (p.Arg472Ter) in one case harbouring primary hereditary microcephaly (MCPH) associated with an inter-hypothalamic adhesion, mixed hearing loss, selective thinning in the retinal nerve fiber layer and parafoveal ganglion cell complex, and short stature. Our findings expand the spectrum of the recently reported neurosensorial abnormalities and revealed the variable phenotype expressivity of CDK5RAP2 defect. Our study highlights the complexity of the genetic background of microcephaly/ID and the efficiency of the exome sequencing to provide an accurate diagnosis and to improve the management and follow-up of such patients., (Copyright © 2021. Published by Elsevier Masson SAS.)

Focal segmental glomerulosclerosis (FSGS) is a histological lesion with many causes, including inherited genetic defects, with significant proteinuria being the predominant clinical finding at presentation. FSGS is considered as a podocyte disease due to the fact that in the majority of patients with FSGS, the lesion results from defects in the podocyte structure. However, FSGS does not result exclusively from podocyte-associated genes. In this study, we used a genetic approach based on targeted next-generation sequencing (NGS) of 242 genes to identify the genetic cause of FSGS in seven Tunisian families. The sequencing results revealed the presence of eight distinct mutations including seven newly discovered ones: the c.538G>A (p.V180M) in NPHS2, c.5186G>A (p.R1729Q) in PLCE1 and c.232A>C (p.I78L) in PAX2 and five novel mutations in COL4A3 and COL4A4 genes. Four mutations (c.209G>A (p.G70D), c.725G>A (p.G242E), c.2225G>A (p.G742E), and c. 1681_1698del) were detected in COL4A3 gene and one mutation (c.1424G>A (p.G475D)) was found in COL4A4. In summary, NGS of a targeted gene panel is an ideal approach for the genetic testing of FSGS with multiple possible underlying etiologies. We have demonstrated that not only podocyte genes but also COL4A3/4 mutations should be considered in patients with FSGS., (© 2021. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Introduction: Hearing impairment (HI) is characterized by complex genetic heterogeneity. The evolution of next generation sequencing, including targeted enrichment panels, has revolutionized HI diagnosis., Objectives: In this study, we investigated genetic causes in 22 individuals with non- GJB2 HI., Methods: We customized a Haloplex HS kit to include 30 genes known to be associated with autosomal recessive nonsyndromic HI (ARNSHI) and Usher syndrome in North Africa., Results: In accordance with the ACMG/AMP guidelines, we report 11 pathogenic variants; as follows; five novel variants including three missense ( ESRRB- Tyr295Cys, MYO15A -Phe2089Leu and MYO7A -Tyr560Cys) and two nonsense (USH1C- Gln122Ter and CIB2- Arg104Ter) mutations; two previously reported mutations (OTOF- Glu57Ter and PNPT1 -Glu475Gly), but first time identified among Tunisian families; and four other identified mutations namely WHRN- Gly808AspfsX11, SLC22A4 -Cys113Tyr and two MYO7A compound heterozygous splice site variants that were previously described in Tunisia. Pathogenic variants in WHRN and CIB2 genes, in patients with convincing phenotype ruling out retinitis pigmentosa, provide strong evidence supporting their association with ARNSHI. Moreover, we shed lights on the pathogenic implication of mutations in PNPT1 gene in auditory function providing new evidence for its association with ARNSHI. Lack of segregation of a previously identified causal mutation OTOA -Val603Phe further supports its classification as variant of unknown significance. Our study reports absence of otoacoustic emission in subjects using bilateral hearing aids for several years indicating the importance of screening genetic alteration in OTOF gene for proper management of those patients., Conclusion: In conclusion, our findings do not only expand the spectrum of HI mutations in Tunisian patients, but also improve our knowledge about clinical relevance of HI causing genes and variants., Competing Interests: The authors declared that there is no conflict of interest., (© 2021 The Authors. Published by Elsevier B.V. on behalf of Cairo University.)

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common monogenic disease that has an adverse impact on the patients' health and quality of life. ADPKD is usually known as "adult-type disease," but rare cases have been reported in pediatric patients. We present here a 2-year-old Tunisian girl with renal cyst formation and her mother with adult onset ADPKD. Disease-causing mutation has been searched in PKD1 and PKD2 using Long-Range and PCR followed by sequencing. Molecular sequencing displayed us to identify a novel likely pathogenic mutation (c.696 T > G; p.C232W, exon 5) in PKD1. The identified PKD1 mutation is inherited and unreported variant, which can alter the formation of intramolecular disulfide bonds essential for polycystin-1 function. We report here the first mutational study in pediatric patient with ADPKD in Tunisia., (© 2020 International Union of Biochemistry and Molecular Biology.)

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare group of disease that affect the tubules of the kidney. There are 4 known subtypes of ADTKD classified based on causative genes and clinical features. In our study, we aimed to identify the causative subtypes of ADTKD in a Tunisian ADTKD family (3 affected members), in whom standard nephrological diagnosis did not provide clear subtype of ADTKD, until genetic testing was performed. Sanger sequencing was performed for UMOD, HNF1β and REN genes. Mutational analysis allowed us to detect a heterozygous mutation in the REN gene: c.1172C > G, (p.T391R) in exon 10. In silico analyses predicted that the novel likely pathogenic mutation affect protein stability and 3D structure. Our study highlights the importance of establishing a genetic diagnosis to identify the subtype of ADTKD for better patient care. To the best of our knowledge, we report here a first Tunisian ADTKD-REN family., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Autosomal Dominant Polycystic Kidney Disease (ADPKD), the most frequent genetic disorder of the kidneys, is characterized by a typical presenting symptoms include cysts development in different organs and a non-cysts manifestations. ADPKD is caused by mutations in PKD1 or PKD2 genes. In this study, we aimed to search for molecular causative defects among PKD1 and PKD2 genes. Eighteen patients were diagnosed based on renal ultrasonography and renal/extra-renal manifestations. Then, Sanger sequencing was performed for PKD1 and PKD2 genes. Multiplex Ligation dependent Probe Amplification method (MLPA) methods was performed for both PKD genes. Mutational analysis of the PKD2 gene revealed the absence of variants and no deletions or duplications of both PKD genes were detected. But three novels mutations i.e. p.S463C exon 7; c. c.11156+2T>C IVS38 and c.8161-1G>A IVS22 and two previously reported c.1522T>C exon 7 and c.412C>T exon 4 mutations in the PKD1 gene were detected. Bioinformatics tools predicted that the novel variants have a pathogenic effects on splicing machinery, pre-mRNA secondary structure and stability and protein stability. Our results highlighted molecular features of Tunisian patients with ADPKD and revealed novel variations that can be utilized in clinical diagnosis and in the evaluation of living kidney donor. To the best of our knowledge, this is the first report of Autosomal Polycystic Kidney Disease in Tunisia., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Mitochondrial diseases are a clinically heterogeneous group of disorders that arise as a result of dysfunction of the mitochondrial respiratory chain. They can be caused by mutations in both nuclear and mitochondrial DNA. In fact, mitochondrial DNA (mtDNA) defects are known to be associated with a large spectrum of human diseases and patients might present wide range of clinical features with various combinations. Our study reported a Tunisian family with clinical features of maternally inherited diabetes and deafness (MIDD). Accordingly, we performed a whole mitochondrial genome mutational analysis, results revealed a haplotype composed by "A750G, A1438G, G8860A, T12705, T14766C and T16519C", in homoplasmic state, in the mother and transmitted to her daughter and her son. The patient with MIDD2 and retinopathy presented, in addition to this haplotype associated to the MIDD, two de novo variations including a novel one m.8241T>G (p. F219C) in MT-CO2 gene and a known one m.13276G>A (p. M314V) in MT-ND5 gene. The coexistence of these two mutations could explain the retinopathy observed in this patient., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Mitochondrial diabetes (MD) is a heterogeneous disorder characterized by a chronic hyperglycemia, maternal transmission and its association with a bilateral hearing impairment. Several studies reported mutations in mitochondrial genes as potentially pathogenic for diabetes, since mitochondrial oxidative phosphorylation plays an important role in glucose-stimulated insulin secretion from beta cells. In the present report, we studied a Tunisian family with mitochondrial diabetes (MD) and deafness associated with nephropathy. The mutational analysis screening revealed the presence of a novel heteroplasmic mutation m.9276G>C in the mitochondrial COIII gene, detected in mtDNA extracted from leukocytes of a mother and her two daughters indicating that this mutation is maternally transmitted and suggest its implication in the observed phenotype. Bioinformatic tools showed that m.9267G>C mutation (p.A21P) is « deleterious » and it can modify the function and the stability of the MT-COIII protein by affecting the assembly of mitochondrial COX subunits and the translocation of protons then reducing the activity of the respective OXPHOS complexes of ATP synthesis. The nonsynonymous mutation (p.A21P) has not been reported before, it is the first mutation described in the COXIII gene which is related to insulin dependent mitochondrial diabetes and deafness and could be specific to the Tunisian population. The m.9267G>C mutation was present with a nonsynonymous inherited mitochondrial homoplasmic variation MT-COI m.5913 G>A (D4N) responsible of high blood pressure, a clinical feature detected in all explored patients., (Copyright © 2015. Published by Elsevier Inc.)

The Bloom syndrome (BS) is an autosomic recessive disorder comprising a wide range of abnormalities, including stunted growth, immunodeficiency, sun sensitivity and increased frequency of various types of cancer. Bloom syndrome cells display a high level of genetic instability, including a 10-fold increase in the sister chromatid exchanges (SCE) level. Bloom syndrome arises through mutations in both alleles of the BLM gene, which was identified as a member of the RecQ helicase family. In this study, we screened a Tunisian family with three BS patients. Cytogenetic analysis showed several chromosomal aberrations, and an approximately 14-fold elevated SCE frequency in BS cells. A significant increase in SCE frequency was observed in some family members but not reaching the BS patients values, leading to suggest that this could be due to the heterozygous profile. Microsatellite genotyping using four fluorescent dye-labeled microsatellite markers revealed evidence of linkage to BLM locus and the healthy members, sharing higher SCE frequency, showed heterozygous haplotypes as expected. Additionally, the direct BLM gene sequencing identified a novel homozygous frameshift mutation c.3617-3619delAA (p.K1207fsX9) in BS patients and a heterozygous BLM mutation in the family members with higher SCE frequency. Our findings suggest that this latter mutation likely leads to a reduced BLM activity explaining the homologous recombination repair defect and, therefore, the increase in SCE. Based on the present data, the screening of this mutation could contribute to the rapid diagnosis of BS. The genetic confirmation of the mutation in BLM gene provides crucial information for genetic counseling and prenatal diagnosis.

The Bloom syndrome (BS) is an autosomal recessive disorder associated with dwarfism, immunodeficiency, reduced fertility and cancer risk. BS cells show genomic instability, particularly an hyper exchange between the sister chromatids due to a defective processing of the DNA replication intermediates. It is caused by mutations in the BLM gene which encodes a member of the RecQ family of DExH box DNA helicases. In this study, we reported cytogenetic, BLM linkage and mutational analyses for two affected Tunisian families. The Cytogenetic parameters were performed by chromosomal aberration (CA) and sister chromatid exchange (SCE) assays and results showed a significant increase in mean frequency of CA and SCE in BS cells. BLM linkage performed by microsatellite genotyping revealed homozygous haplotypes for the BS patients, evidence of linkage to BLM gene. Mutational analysis by direct DNA sequencing revealed a novel frameshift mutation (c.1980-1982delAA) in exon 8 of BLM gene, resulting in a truncated protein (p.Lys662fsX5). The truncated protein could explain genomic instability and its related symptoms in the BS patients. The screening of this mutation is useful for BS diagnosis confirmation in Tunisian families., (© 2013 European Academy of Dermatology and Venereology.)

Hearing loss is a common congenital anomaly with an incidence of 1 in 1000 live births. It has been described together with several other clinical features as fortuitous association or commune genetic syndrome. In this study, we investigated a consanguineous Tunisian family with moderate to profound congenital hearing loss, mental retardation and autistic behaviors. We performed a genome wide microarray analysis study using approximately 300,000 SNPs in a common set of 7 invidious of this family. We identified regions of suggestive linkage with hearing loss on chromosomes 6p12 and 7q34. In addition, we identified a deletion on chromosome 8p in the two autistic individuals. This report presents an illustration of how consanguinity could increase familial clustering of multiple hereditary diseases within the same family. The application of next generation sequencing for this family seems to be a good strategy for further analysis leading to the identification of candidate genes., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The genetic polymorphisms in DNA repair genes might affect the repair activities of the enzymes, predisposing individuals to cancer risk. Due to these genetic variants, interethnic differences in DNA repair capacity were observed in various populations. Hence, our study aimed to determine the prevalence of three nonsynonymous single-nucleotide polymorphisms (SNPs) in an X-ray repair cross-complementation group 1 gene (XRCC1) (Arg194Trp, Arg280His, and Arg399Gln) in a healthy Tunisian population (TUN) and to compare that with HapMap ( www.hapmap.org ) populations. Also, we predicted their eventual functional effect based on the protein conservation analysis by Sorting Intolerant From Tolerant (SIFT; http://sift.jcvi.org/www/SIFT_dbSNP.html ) software. The genotypes of 154 healthy individuals were determined by the polymerase chain reaction-restriction fragment length polymorphism. Tunisians showed a relative relatedness with Caucasians (European ancestry) for Arg194Trp and Arg399Gln that may be explained by the strategic geographic location of Tunisia in the Mediterranean, allowing exchanges with European countries. However, a characteristic pattern was observed in Arg280His polymorphism, which could be explained by the high inbreeding rate in TUN. The analysis of protein conservation showed that the three amino acid substitutions were predicted as damaged. The results presented here provide the first report on XRCC1 polymorphisms about Tunisians and may establish baseline database for our future clinical and genetic studies.

Genetic polymorphisms in DNA repair genes might influence the repair activities of the enzymes predisposing individuals to cancer risk. Owing to the presence of these genetic variants, interethnic differences in DNA repair capacity have been observed in various populations. The present study was undertaken to determine the allele and genotype frequencies of two common non-synonymous SNPs, XRCC3 p.Thr241>Met (C > T, rs861539) and XPD p.Lys751>Gln (T > G, rs13181) in a healthy Tunisian population and to compare them with HapMap ( http://www.hapmap.org/ ) populations. Also, we predicted their eventual functional effect based on bioinformatics tools. The genotypes of 154 healthy and unrelated individuals were determined by PCR-RFLP procedure. Our findings showed a close relatedness with Caucasians from European ancestry which might be explained by the strategic geographic location of Tunisia in the Mediterranean, thus allowing exchanges with Europeans countries. The in silico predictions showed that p.Thr241>Met substitution in XRCC3 protein was predicted as possibly damaging, indicating that it is likely to have functional consequences as well. To the best of our knowledge, this is the first study in this regard in Tunisia. So, these data could provide baseline database and help us to explore the relationship of XRCC3 and XPD polymorphisms with both cancer risk and DNA repair variability in our population.

Genetic polymorphisms in glutathione S-transferases (GSTs) genes might influence the detoxification activities of the enzymes predisposing individuals to cancer risk. Owing to the presence of these genetic variants, inter-individual and ethnic differences in GSTs detoxification capacity have been observed in various populations. Therefore, the present study was performed to determine the prevalence GSTM1 0/0, GSTT1 0/0, GSTP1 Ile(105)Val, and GSTA1 A/B polymorphisms in 154 healthy individuals from South Tunisia, and to compare them with those observed in North and Centre Tunisian populations and other ethnic groups. GSTM1 and GSTT1 polymorphisms were analyzed by a Multiplex-PCR approach, whereas GSTP1 and GSTA1 polymorphisms were examined by PCR-RFLP. The frequencies of GSTM10/0 and GSTT1 0/0 genotypes were 53.9% and 27.9%, respectively. The genotype distribution of GSTP1 was 47.4% (Ile/Ile), 40.9% (Ile/Val), and 11.7% (Val/Val). For GSTA1, the genotype distribution was 24.7% (A/A), 53.9% (A/B), and 21.4% (B/B). The combined genotypes distribution of GSTM1, GSTT1, GSTP1 and GSTA1 polymorphisms showed that thirty one of the 36 possible genotypes were present in our population; eight of them have a frequency greater than 5%. To the best of our knowledge, this is the first report of GSTs polymorphisms in South Tunisian population. Our findings demonstrate the impact of ethnicity and reveal a characteristic pattern for Tunisian population. The molecular studies in these enzymes provide basis for further epidemiological investigations in the population where these functional polymorphisms alter therapeutic response and act as susceptibility markers for various clinical conditions., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Cigarette smoking is a major public health problem in Tunisia as it concerns up to 30-35% of the adult population, raising important national issues on tobacco-related disease. The aim of this study was to establish whether cigarette smoking increases sister chromatid exchange (SCE) in peripheral blood lymphocytes of smokers (n=14) compared with non-smokers (n=15) in Sfax, Tunisia. The smokers were subdivided in two subgroups according to the duration of the smoking habit: heavy smokers (>10 years) and light smokers (≤10 years). After signing a consent form, volunteers provided a blood sample (5ml) to establish cell cultures during 72h. For SCE analysis, 30 second-division metaphases were examined from each subject. We determined the frequency of SCE, the percentage of high-frequency cells (HFC) and that of the high-frequency cell individual (HFI). The results show a significantly higher SCE frequency in smokers (8.65±1.43) than in non-smokers (7.16±1.3; p<0.01). A significant difference in SCE frequency was also shown when comparing the two subgroups of smokers (p<0.05). Interestingly, no significant difference was found when comparing the light smokers with non-smokers (7.82±1 vs 7.16±1.3, respectively, p>0.05). The percentages of HFC and HFI were significantly higher in smokers (11.2±7.8% and 78.6%, respectively) than in non-smokers (4±2.2% and 20%, respectively, p<0.01). Our study indicates that the genotoxic effects in lymphocytes from healthy Tunisian smokers are most likely caused by cigarette-smoke constituents. This effect was mainly observed in smokers who had been smoking during more than 10 years. These results provide scientific evidence to urge the prevention of tobacco consumption., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Susceptibility to type 1 diabetes mellitus is strongly associated with particular HLA class II alleles. However, non HLA genetic factors are likely to be required for the development of disease. The candidate genes include the cytotoxic T lymphocyte associated 4 (CTLA-4) located on chromosome 2q33 and designated (IDDM12), which encodes a cell surface negative signal T molecule providing for activation. We investigated CTLA-4 exon 1 dimorphism in 74 type 1 patients and a control group of 48 healthy subjects from Tunisia using two methods PCR (polymerase chain reaction) allele specific and polymerase chain reaction restriction fragment length polymorphism (PCR RFLP). The CTLA-4/G allele was found on 68.9% in type 1 patients as compared to 51.02% in controls (p = 0.002), mostly in homozygous from 43.24% versus 22.45% (p = 0.0058). This results indicate that CTLA-4/G allele was significantly associated with predisposition to type 1 diabetes in our group from Tunisian population.