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BackgroundVariants in the Hepatocyte Nuclear Factor 1 Alpha gene (HNF1A) are associated with lipoproteins levels and type 2 diabetes. In this study, we aimed to assess the association ofHNF1Agene and haplotypes with the metabolic syndrome... more
BackgroundVariants in the Hepatocyte Nuclear Factor 1 Alpha gene (HNF1A) are associated with lipoproteins levels and type 2 diabetes. In this study, we aimed to assess the association ofHNF1Agene and haplotypes with the metabolic syndrome (MetS) and its components through an association study in the Tunisian population as well as by a meta-analysis.MethodsA total of 594 Tunisian individuals were genotyped for three variants (rs1169288, rs2464196 and rs735396) located inHNF1Agene using KASPar technology. Statistical analyses were performed with R software. The association was furthermore evaluated through a meta-analysis of our results with those obtained in a Moroccan population.ResultsOur results showed no association betweenHNF1Avariants and MetS in the Tunisian population. However, a significant association was observed between the variant rs735396 and a higher waist circumference. The stratified analysis according to the sex highlighted a significant association between the vari...
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The identification of underlying genes of genetic conditions has expanded greatly in the past decades, which has broadened the field of genes responsible for inherited neuromuscular diseases. We aimed to investigate mutations associated... more
The identification of underlying genes of genetic conditions has expanded greatly in the past decades, which has broadened the field of genes responsible for inherited neuromuscular diseases. We aimed to investigate mutations associated with neuromuscular disorders phenotypes in 2 Moroccan families. Next-generation sequencing combined with Sanger sequencing could assist with understanding the hereditary variety and underlying disease mechanisms in these disorders. Two novel homozygous mutations were described in this study. The SIL1 mutation is the first identified in the Moroccan population, the mutation was identified as the main cause of Marinesco-Sjogren syndrome in one patient. While the second mutation identified in the fatty acid 2-hydroxylase gene (FA2H) was associated with the Spastic paraplegia 35 in another patient, both transmitted in an autosomal recessive pattern. These conditions are extremely rare in the North African population and may be underdiagnosed due to overl...
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The aim of the present study is to explore the association between the APOA5 polymorphisms and haplotypes with obesity in Moroccan patients. The study was performed in 459 subjects, Obese (n = 164) and non-obese (n = 295). All subjects... more
The aim of the present study is to explore the association between the APOA5 polymorphisms and haplotypes with obesity in Moroccan patients. The study was performed in 459 subjects, Obese (n = 164) and non-obese (n = 295). All subjects were genotyped for the APOA5 -1131T > C (rs662799) and c.56C > G (rs3135506) polymorphisms. The contribution of APOA5 polymorphisms and haplotypes in the increased risk of obesity were explored using logistic regression analyses. The -1131T > C and c.56C > G polymorphisms were significantly associated with obesity. Both polymorphisms were strongly associated with increased BMI. Analysis of constructed haplotypes showed a significant association between CG haplotype and susceptibility to obesity (OR [95%CI] = 3.09 [1.93–4.97]; P < 0.001). These results support a potential role for APOA5 common variants and related haplotypes as risk factors for obesity. 2015 Elsevier Masson SAS. All rights reserved.
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Research Interests: Genetics, Cognitive Science, Morocco, Medicine, Humans, and 10 moreChild, Mutation, Male, Gene, Abcd, ABCD, Leukodystrophy, Neurosciences, Exon, and Nonsense Mutation
BackgroundInherited retinal dystrophies (IRD) and optic neuropathies (ION) are the two major causes world-wide of early visual impairment, frequently leading to legal blindness. These two groups of pathologies are highly heterogeneous and... more
BackgroundInherited retinal dystrophies (IRD) and optic neuropathies (ION) are the two major causes world-wide of early visual impairment, frequently leading to legal blindness. These two groups of pathologies are highly heterogeneous and require combined clinical and molecular diagnoses to be securely identified. Exact epidemiological studies are lacking in North Africa, and genetic studies of IRD and ION individuals are often limited to case reports or to some families that migrated to the rest of the world. In order to improve the knowledge of their clinical and genetic spectrums in North Africa, we reviewed published data, to illustrate the most prevalent pathologies, genes and mutations encountered in this geographical region, extending from Morocco to Egypt, comprising 200 million inhabitants.Main bodyWe compiled data from 413 families with IRD or ION together with their available molecular diagnosis. The proportion of IRD represents 82.8% of index cases, while ION accounted f...
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H syndrome is an autosomal recessive syndrome, which affects the skin and some vital organs, it is caused by mutations in the SLC29A3 gene, encoding the human equilibrative nucleoside transporter hENT3. This report describes a patient... more
H syndrome is an autosomal recessive syndrome, which affects the skin and some vital organs, it is caused by mutations in the SLC29A3 gene, encoding the human equilibrative nucleoside transporter hENT3. This report describes a patient with typical features of H syndrome. Based on the patient's clinical features, SLC29A3 was selected for molecular investigation. Through direct sequencing, a compound heterozygous alteration in the SLC29A3 gene was found. The c.243delA frameshift mutation leading to a premature termination, resulting in a truncated protein, and a splice site mutation c.300+1G>C predicted to cause a splicing error. This contribution extends the clinical variability of compound heterozygous SLC29A3 mutations resulting in an additional multisystemic manifestation of the clinical spectrum of SLC29A3 disorders.
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Omenn syndrome (OS) is a type of severe combined immunodeficiency (SCID) that is distinguished by, lymphadenopathy, hepatosplenomegaly, erythroderma, alopecia with normal to elevated T-cell counts, eosinophilia, and elevated serum IgE... more
Omenn syndrome (OS) is a type of severe combined immunodeficiency (SCID) that is distinguished by, lymphadenopathy, hepatosplenomegaly, erythroderma, alopecia with normal to elevated T-cell counts, eosinophilia, and elevated serum IgE levels. Recombination activation gene (RAG) 1 or RAG2 mutations that result in partial V(D)J recombination activity are known to be the main cause of OS. Other genes (DCLRE1C, LIG4, IL7RA, common gamma chain, ADA, RMRP, and CHD7) have also been linked to OS, although with low frequency. Here, we report a two-month-old Moroccan girl from consanguineous marriage with chronic diarrhea, recurrent and opportunistic infections, failure to thrive, desquamative erythroderma, hepatosplenomegaly, and axillary lymphadenitis. The immunological assessment showed normal lymphocyte and NK cell counts but an absence of B cells, agammaglobulinemia contrasting with a high level of IgE. On the other hand, Sanger sequencing of RAG1 and RAG2 exon 2 regions revealed a new homozygous deleterious mutation in the RAG1 gene. This c.1184C > T mutation caused a change from Proline to Leucine at position 395 of the protein, leading to a partial loss of function. Early and rapid diagnosis of the disease may facilitate urgent life-saving treatment.
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Investment in Africa over the past year with regards to SARS-CoV-2 genotyping has led to a massive increase in the number of sequences, exceeding 100,000 genomes generated to track the pandemic on the continent. Our results show an... more
Investment in Africa over the past year with regards to SARS-CoV-2 genotyping has led to a massive increase in the number of sequences, exceeding 100,000 genomes generated to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence within their own borders, coupled with a decrease in sequencing turnaround time. Findings from this genomic surveillance underscores the heterogeneous nature of the pandemic but we observe repeated dissemination of SARS-CoV-2 variants within the continent. Sustained investment for genomic surveillance in Africa is needed as the virus continues to evolve, particularly in the low vaccination landscape. These investments are very crucial for preparedness and response for future pathogen outbreaks.One-Sentence SummaryExpanding Africa SARS-CoV-2 sequencing capacity in a fast evolving pandemic.
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Meiotic chromosomes endure rapid prophase movements that ease the formation of interhomologue recombination intermediates that drive synapsis, crossing over, and segregation process. To generate these fast moves, the meiotic telomere... more
Meiotic chromosomes endure rapid prophase movements that ease the formation of interhomologue recombination intermediates that drive synapsis, crossing over, and segregation process. To generate these fast moves, the meiotic telomere complex (MTC) enables telomere-inner nuclear membrane attachment during meiotic prophase I and transfers cytoskeletal signals via another complex: the LINC complex. Furthermore, disruption or mutations of any of the MTC genes (TERB1, TERB2, and MAJIN) alters telomere association with the nuclear envelope leading to impairment of homologous pairing and synapsis, a meiotic arrest, and consequently to male infertility. To decipher the effect of TERB1, TERB2, and MAJIN missense mutations on protein structure, stability, and function, different bioinformatic tools were used in this study including VEP, Mutabind2, Haddock, Prodigy, Ligplot, ConSurf, DUET and MusiteDeep. In total, thirty mutations were predicted to be deleterious using VEP web server: seventee...
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Leukocyte adhesion deficiency type 1 (LAD1) is a rare autosomal recessive hereditary disorder characterized by recurrent infections, impaired pus formation, delayed wound healing, omphalitis, and delayed separation of the umbilical cord... more
Leukocyte adhesion deficiency type 1 (LAD1) is a rare autosomal recessive hereditary disorder characterized by recurrent infections, impaired pus formation, delayed wound healing, omphalitis, and delayed separation of the umbilical cord as hallmark features of the disease. It results from mutations in the integrin β2 subunit gene ITGB2, which encodes the integrin beta chain-2 protein CD18. In this study, we aimed to investigate the case of a five-month-old boy who presented with a clinical phenotype and flow cytometry results suggesting LAD1 disease. Sanger sequencing of all exons and intron boundaries of ITGB2 identified a novel in-frame deletion in exon 7 (ITGB2 c.844_846delAAC, p.Asn282del) in the patient. The p.Asn282del mutation was heterozygous in the child’s parents, whereas it was absent in the 96 control individuals from North Africa. This variant was evaluated by two in silico mutation analysis tools, PROVEAN and MutationTaster, which predicted that the mutation was likely...
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Genetic causes of male infertility are abnormalities in chromosome numbers and/or structures, Y-chromosome deletions and gene mutations. Genetic screening of male infertility is rarely done in our country. The purpose of the study was to... more
Genetic causes of male infertility are abnormalities in chromosome numbers and/or structures, Y-chromosome deletions and gene mutations. Genetic screening of male infertility is rarely done in our country. The purpose of the study was to investigate the frequencies and types of Y chromosome microdeletions in infertile men, based on studies done in the Human Genetics Laboratory of the Pasteur Institute in Morocco. A total of 543 infertile men were screened for Y chromosome microdeletions. The prevalence of AZF Y-chromosome microdeletions among infertile men range from 3% to 10% depending on patients selected. The most frequent microdeletions were detected in the AZFc region, followed by AZFbc, AZFb, AZFa, AZFab. These results indicate the need for Y chromosome microdeletion screening for better management of infertile patients.We hope to encourage use of genetic diagnosis and also research in this field to initiate collaboration for clinical management and appropriate genetic diagno...
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<p>The TDC and TLBc functional domains are represented on the TBC1D24 protein structure. The amino-acid changes identified in this work (in bold) and the published recessive and dominant mutations responsible for NHSL are shown on... more
<p>The TDC and TLBc functional domains are represented on the TBC1D24 protein structure. The amino-acid changes identified in this work (in bold) and the published recessive and dominant mutations responsible for NHSL are shown on the top, while mutations responsible for DOORS syndrome, familial infantile myoclonic epilepsy, progressive myoclonus epilepsy and early-infantile epileptic encephalopathy-16 are shown below the protein structure.</p
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Background: The recombination-activating gene 1 and 2 (RAG1/RAG2) proteins are essential to initiate the V(D)J recombination process, the result is a diverse repertoire of antigen receptor genes and the establishment of the adaptive... more
Background: The recombination-activating gene 1 and 2 (RAG1/RAG2) proteins are essential to initiate the V(D)J recombination process, the result is a diverse repertoire of antigen receptor genes and the establishment of the adaptive immunity. RAG1 mutations can lead to multiple forms of combined immunodeficiency. Methods: In this report, whole exome sequencing was performed in a Moroccan child suffering from combined immunodeficiency, with T and B lymphopenia, autoimmune hemolytic anemia, and cytomegalovirus (CMV) infection. Results: After filtering data and Sanger sequencing validation, one homozygous mutation c.2446G>A (p.Gly816Arg) was identified in the RAG1 gene. Conclusion: This finding expands the spectrum of immunological and genetic profiles linked to RAG1 mutation, it also illustrates the necessity to consider RAG1 immunodeficiency in the presence of autoimmune hemolytic anemia and CMV infection, even assuming the immunological phenotype appears more or less normal.
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Early Infantile Epileptic Encephalopathy (known as Ohtahara Syndrome) is one of the most severe and earliest forms of epilepsy, characterized by early seizures onset. It affects newborns and children between two and six years old. Among... more
Early Infantile Epileptic Encephalopathy (known as Ohtahara Syndrome) is one of the most severe and earliest forms of epilepsy, characterized by early seizures onset. It affects newborns and children between two and six years old. Among the genes that have been associated with early infantile epileptic encephalopathy, the STXBP1 gene, which encodes the Syntaxin binding protein1a that is involved in SNARE complex formation, contributes to synaptic vesicles exocytosis. The aim of this study was to identify the most pathogenic polymorphisms of STXBP1 gene and determine their impact on the structure and stability of Stxbp1 protein. The high-risk nonsynonymous single nucleotide polymorphisms (nsSNPs) in the STXBP1 gene were predicted using 13 bioinformatics tools. The conservation analysis was realized by CONSURF web server. The analysis of the impact of the pathogenic SNPs on the structure of Stxbp1 protein was realized using YASARA software, and the molecular dynamics simulation was pe...
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Mutations in the mesenchymal epithelial transition factor (MET) gene are frequently associated with multiple human cancers but can also lead to human non-syndromic autosomal recessive deafness (DFNB97). In the present study, we identified... more
Mutations in the mesenchymal epithelial transition factor (MET) gene are frequently associated with multiple human cancers but can also lead to human non-syndromic autosomal recessive deafness (DFNB97). In the present study, we identified a novel homozygous missense mutation in the METgene causing a non-syndromic hearing impairment DFNB97 form. Whole-exome sequencing was performed to determine the genetic causes of hearing loss in a Moroccan consanguineous family with an affected daughter. The structural analysis of native and mutant in the SEMA domain of the MET receptor was investigated using a molecular dynamics simulation (MDS) approach. We identified a novel pathogenic homozygous c.948A>G (p.Ile316Met) mutation in the MET gene in one deaf Moroccan young girl carrying a total bilateral non-syndromic hearing impairment. The results of the MDS approach show that an Ile316Met mutation in the SEMA domain leads to protein flexibility loss. This may produce a major impact on the st...
Research Interests: Genetics, Biology, Medicine, Mutation, Moroccan Family law, and 3 moreHearing Loss, Gene, and Exome Sequencing
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The aim of the present study was to determine the frequency and nature of chromosomal abnormalities involved in patients with the clinical spectrum of ambiguous genitalia (AG), amenorrhea, and Turner phenotype, in order to compare them... more
The aim of the present study was to determine the frequency and nature of chromosomal abnormalities involved in patients with the clinical spectrum of ambiguous genitalia (AG), amenorrhea, and Turner phenotype, in order to compare them with those reported elsewhere. The study was conducted in the Cytogenetic Department of Pasteur Institute of Morocco, and it reports on the patients who were recruited between 1996 and 2016. Cytogenetic analysis was performed according to the standard method. Among 1,415 patients, chromosomal abnormalities were identified in 7.13% (48/673) of patients with AG, 17.39% (28/161) of patients with primary amenorrhea (PA), 4% (1/25) of patients with secondary amenorrhea, and 23.20% (129/556) of patients with Turner phenotype. However, Turner syndrome was diagnosed in 0.89% (6/673) of patients with AG, 10.56% (17/161) of patients with PA, and 19.78% (110/556) of patients with Turner phenotype. In addition, Klinefelter syndrome and mixed gonadal dysgenesis we...
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Recent studies have shown an inverse relationship between diabetes and prostate-specific antigen (PSA) levels. In this study, we sought to evaluate the PSA levels in serum of diabetic and non-diabetic Moroccan males. In a cross-sectional... more
Recent studies have shown an inverse relationship between diabetes and prostate-specific antigen (PSA) levels. In this study, we sought to evaluate the PSA levels in serum of diabetic and non-diabetic Moroccan males. In a cross-sectional study, four hundred and seventy diabetic and 869 non-diabetic males were screened from January 2015 to April 2016 at Pasteur institute of Morocco. Hemoglobin A1c and Fasting Blood Glucose were measured using high performance liquid chromatography and dry chemistry, respectively. We used a chemiluminescent microparticle immunoassay technology to evaluate the levels of Serum PSA and testosterone. Overall, the PSA levels have revealed no significant difference between diabetic and non-diabetic males (1.31 ± 0.04ng/mL vs.1.36 ± 0.03ng/mL, p = 0.380, respectively). The PSA levels increased with age both in non-diabetics and diabetics. Moreover, in diabetic subjects the PSA levels were less age dependent (p =0.002) than in non-diabetic (p amplt; 0.0001). The stratified analysis showed that the PSA was significantly lower in diabetic than in non-diabetic subjects aged between 50-59 years (p= 0.0004). Furthermore, no significant testosterone concentrations were observed in subjects with or without diabetes (p= 0.904). Our results shows that the PSA levels are age-dependant in diabetic and non-diabetic males but PSA levels is affected by diabetes status only in the group aged between 50-59 years.
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Ataxia-telangiectasia (AT) is a rare autosomal recessive disease, affecting neurologic and immune system. Numerous mutations are described in the ATM gene in several populations. However, in Morocco, few data are available concerning this... more
Ataxia-telangiectasia (AT) is a rare autosomal recessive disease, affecting neurologic and immune system. Numerous mutations are described in the ATM gene in several populations. However, in Morocco, few data are available concerning this condition. Our main goal is to determine clinical, immunological, and molecular presentation of Moroccan patients with AT. We screened 27 patients, out of 22 unrelated families, for ATM gene mutations. All our patients showed ataxia, ocular telangiectasia, and immunodeficiency, as well as elevated serum alphafetoprotein levels. Mean age at diagnosis was 5.51 years, and consanguinity rate was 81.8 %. Mean age at onset was 2.02 years, and mean time to diagnosis was 3.68 years. We found 14 different mutations in 19 unrelated families, of which 7 were not reported. Our results showed that c.5644C&amp;amp;amp;amp;amp;amp;amp;amp;gt;T mutation was the most common in our series. However, further studies are required to demonstrate a founder effects on ATM gene in Moroccan patients, who showed mutational heterogeneity otherwise. Our data indicate that direct sequencing of coding exons is sufficient for a high detection rate in ATM in Moroccan population.
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The objective of this study is to determine the genetic cause of the disorder of sex development on Moroccan family. Indeed, the genomics and human genetics laboratory at the Pasteur Institute of Morocco recruited four brothers with... more
The objective of this study is to determine the genetic cause of the disorder of sex development on Moroccan family. Indeed, the genomics and human genetics laboratory at the Pasteur Institute of Morocco recruited four brothers with ambiguous genitalia. Cytogenetic analysis of the first brother revealed the presence of a chimeric karyotype 46, XX/46, XY with the presence of the SRY gene. The other three brothers present a normal female karyotype 46, XX with the presence of the SRY gene.
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Abstract- Metabolic syndrome (MS) is regarded as a real public health problem its prevalence rises each year as well as its morbidity. It is a multi factorial disease and besides environmental factors and genetic factors also contribute... more
Abstract- Metabolic syndrome (MS) is regarded as a real public health problem its prevalence rises each year as well as its morbidity. It is a multi factorial disease and besides environmental factors and genetic factors also contribute to the pathogenesis of MS. In several studies the SstI (3238C> G) polymorphism of APOC3 gene is associated with increased plasma concentrations of triglyceride (TG) and hypertriglyceridemia. The aim of the present study was to determine the association between polymorphism 3238C> G in APOC3, and Metabolic Syndrome in the Moroccan Population. Statistical analysis has revealed an association of polymorphism APOC3 3238C>G susceptibility with the metabolic syndrome in two models, codominant 1 [OR = 4.21 [1.66-10.68], p = 0.0008] and dominant [OR = 3.83 [1.59-9.19] p = 0.0010]. The variant APOC3 3238G were associated with elevated TG levels (P = 0.0146) and LDL-C (p = 0.0068) compared to patients with MS and controls non-carriers of this variant.
Biallelic mutations in <i>ACO2</i>, encoding the mitochondrial aconitase 2, have been identified in individuals with neurodegenerative syndromes, including infantile cerebellar retinal degeneration and recessive optic... more
Biallelic mutations in <i>ACO2</i>, encoding the mitochondrial aconitase 2, have been identified in individuals with neurodegenerative syndromes, including infantile cerebellar retinal degeneration and recessive optic neuropathies (locus OPA9). By screening European cohorts of individuals with genetically unsolved inherited optic neuropathies, we identified 61 cases harbouring variants in <i>ACO2</i>, among whom 50 carried dominant mutations, emphasizing for the first time the important contribution of <i>ACO2</i> monoallelic pathogenic variants to dominant optic atrophy. Analysis of the ophthalmological and clinical data revealed that recessive cases are affected more severely than dominant cases, while not significantly earlier. In addition, 27% of the recessive cases and 11% of the dominant cases manifested with extraocular features in addition to optic atrophy. <i>In silico</i> analyses of <i>ACO2</i> variants predicted...
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Twelve Y-chromosomal short tandem repeats (STRs), DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS388, DYS426 and DYS439 were typed in Berber-speaking (n ¼ 49) and Arabic-speaking (n ¼ 60) population samples from... more
Twelve Y-chromosomal short tandem repeats (STRs), DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS388, DYS426 and DYS439 were typed in Berber-speaking (n ¼ 49) and Arabic-speaking (n ¼ 60) population samples from Morocco. #
Copyright © 2014 Khaled Lasram et al.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is... more
Copyright © 2014 Khaled Lasram et al.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Aims. Genetic association studies have reported the E23K variant of KCNJ11 gene to be associated with Type 2 diabetes. In Arab populations, only four studies have investigated the role of this variant. We aimed to replicate and validate the association between the E23K variant and Type 2 diabetes in Tunisian and Arab populations. Methods. We have performed a case-control association study including 250 Tunisian patients with Type 2 diabetes and 267 controls. Allelic association has also been evaluated by 2 meta-analyses including all population-based studies among Tunisians and Arabs (2 and 5 populations, resp.). Results. A significant association between the E23K variant and Type 2 diabetes was found (OR = 1.6, 95 % CI = 1.14–2.27, and
Neurosciences de Montpellier, Génétique et thérapie des cécités rétiniennes et neuropathies optiques héréditaires, INSERM U-1051,
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Since December 2019, the recent outbreak of coronavirus disease (COVID - 19) has continued to spread drastically around the world. To date, no approved drug or vaccine is av ailable to treat or prevent this new coronavirus (SARS - CoV -... more
Since December 2019, the recent outbreak of coronavirus disease (COVID - 19) has continued to spread drastically around the world. To date, no approved drug or vaccine is av ailable to treat or prevent this new coronavirus (SARS - CoV - 2) infection. Unprecedented global effort has been made by researchers to understand the various routes of SARS - CoV - 2 virus transmission in order to effectively prevent the contamination. In this r eview, we discuss the updated literature regarding the different mo des of SARS - CoV - 2 transmission.
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L’expression membranaire des molecules du complexe majeur d’histocompatibilite de classe II (CMH-II) joue un role crucial dans les phenomenes de presentation des antigenes aux lymphocytes T CD4+ et de declenchement de la reponse immune.... more
L’expression membranaire des molecules du complexe majeur d’histocompatibilite de classe II (CMH-II) joue un role crucial dans les phenomenes de presentation des antigenes aux lymphocytes T CD4+ et de declenchement de la reponse immune. Les deficits immunitaires dus au defaut d’expression de ces molecules constituent un ensemble heterogene d’affections hereditaires rares de transmission autosomique recessive. Ce desordre est du a la presence d’une anomalie genetique de l’un des 4 genes CIITA , RFXANK , RFX5 et RFXAP codants pour les proteines impliquees dans la regulation de la transcription des genes CMH II. La majorite des cas rapportes dans la litterature sont d’origine maghrebine. Ce deficit est caracterise cliniquement par de nombreuses infections notamment digestives et pulmonaires qui apparaissent tot dans la vie. C’est une affection encore meconnue dans notre pays par les cliniciens. Ce travail resume la strategie de diagnostic du deficit des molecules CMH II suivie par l’Un...
Introduction: Auditory neuropathy is a hearing disorder where outer hair cell function within the cochlea is normal, but inner hair cell and/or the auditory nerve function is disrupted. It is a heterogeneous disorder, which can have... more
Introduction: Auditory neuropathy is a hearing disorder where outer hair cell function within the cochlea is normal, but inner hair cell and/or the auditory nerve function is disrupted. It is a heterogeneous disorder, which can have either congenital or acquired causes. Methods: We found a disease-segregating mutation in the X-linked AIFM1 gene through whole-exome sequencing, encoding the apoptosis-inducing factor mitochondrion-associated 1. Results: The impact of the c.1045A>G; p.(Ser349Gly) mutation on the AIFM1 protein was predicted using different bioinformatics tools. The pedigree analysis in the examined family was consistent with X-linked dominant inheritance. Discussion/Conclusion: To our knowledge, this is the first study that identifies a mutation in the AIFM1 gene in Moroccan patients suffering from X-linked auditory neuropathy.
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The SARS-cov-2 RNA dependent RNA polymerase (nsp12) is a crucial viral enzyme that catalyzes the replication of RNA from RNA templates. The fixation of some ligands in the active site may alter the viral life cycle. The aim of the present... more
The SARS-cov-2 RNA dependent RNA polymerase (nsp12) is a crucial viral enzyme that catalyzes the replication of RNA from RNA templates. The fixation of some ligands in the active site may alter the viral life cycle. The aim of the present study is to identify the conservation level of nsp12 motifs (A-G), using consurf server, and discover their interactions with rifabutin, rifampicin, rifapentin, sorangicin A, streptolydigin, myxopyronin B, VXR and VRX using AutoDockTools-1.5.6, Gromacs 2018.2 and g-mmpbsa. Thus, the most of amino acids residues located in nsp12 protein Motifs (A-G) were predicted as highly conserved. The binding energies of streptolydigin, VXR, rifabutin, rifapentine, VRX, sorangicin A, myxopyronin B and rifampicin with nsp12 protein are -8.11, -8.23, -7.14, -6.94, -6.55, -5.46, -5.33 and -5.26 kcal/mol, respectively. In the other hand, the binding energies of ligand in the same order with nsp7-nsp8-nsp12 complex are -7.23, -7.08, -7.21, -7, -6.59, -8.73, -5.52, -5.87 kcal/mol, respectively. All ligands interact with at least two nsp12 motifs. The molecular dynamics simulation of nsp12-streptolydigin and nsp12-VXR complexes shows that these two complexes are stable and the number of hydrogen bonds as a function of time, after 30 ns of simulation, varies between 0 and 6 for nsp12-streptolydigin complex and between 0 and 4 for nsp12-VXR complex. The average of free binding energies obtained using g_mmpbsa, after 30 ns of simulation, is -191.982 Kj/mol for nsp12-streptolydigin complex and -153.583 Kj/mol for nsp12-VXR complex. Our results suggest that these ligands may be used as inhibitors of SARS-cov-2 nsp12 protein. Communicated by Ramaswamy H. Sarma.
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Apolipoprotein A5 (APOA5) has been linked to metabolic syndrome (MetS) in several populations. In North Africa, only the Tunisian and Moroccan populations were investigated. Our aim is to assess the association between APOA5 gene variant... more
Apolipoprotein A5 (APOA5) has been linked to metabolic syndrome (MetS) in several populations. In North Africa, only the Tunisian and Moroccan populations were investigated. Our aim is to assess the association between APOA5 gene variant (rs662799) and haplotypes with MetS in Tunisian population and to perform a meta-analysis in North Africa. A total of 594 Tunisian participants were genotyped for polymorphism rs662799 using KASPar technology. Two polymorphisms rs3135506 and rs651821 in APOA5 gene genotyped in our previous study, were used in addition to rs662799 to assess the haplotype association with MetS. The genotype of 875 participants was used for the meta-analysis. Statistical analyses were performed with R software. The rs662799 increases the risk of MetS under the dominant (P=0.018) and the additive models (P=0.028) in the Tunisian population. After stratification of the cohort following the sex and the geographic origin, a positive association of rs662799 with MetS was fo...