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S Abdelhak

Publications and source records attributed to S Abdelhak.

At least 19 recordsLinked to original sources
PubMed2006

[Homozygous antithrombin type HBS deficiency; a family study].

Congenital antithrombin (AT) deficiency is the most thrombotic genetic abnormality of haemostasis. Total quantitative deficits are lethal as early as life intra-uterine. Only homozygous mutations concerning the heparin-binding site are compatible with life. We report here the case of an 18 years old patient with recurrent deep venous thrombosis of the inferior members. Haemostasis exploration shows a decreased AT activity (11%) in the presence of heparin while AT progressive activity and AT antigen are normal. Two other homozygous sisters are identified in this family study. Molecular study of AT gene show Arg47-Cys substitution, already reported in the literature with patients of different geographic origins. Treatment of patients with homozygous AT type HBS deficiency is similar that for patients with heterozygous AT deficiency; a continuous prophylactic anticoagulant treatment is always necessary and AT concentrates infusions are required in all situations needing curative heparin treatment.

Adolescent↗
PubMed2006

Genetic and mutational heterogeneity of autosomal recessive chronic granulomatous disease in Tunisia.

NADPH oxidase, a multi-subunit protein consisting of cytosolic components and the membrane-bound heterodimer, plays an instrumental role in host defence mechanisms of phagocytes. Genetic deficiency of the enzymatic complex results in an inherited disorder, chronic granulomatous disease (CGD), which is characterized by an impaired phagocyte microbicidal activity. X-Linked (XL) CGD results from a mutation in the CYBB gene encoding the gp91phox subunit, while autosomal recessive (AR) CGD is associated with mutations in one of the NCF1, NCF2 and CYBA genes that encode the p47phox, p67phox and p22phox subunits, respectively. In the study reported here, we investigated genetic defects underlying CGD in 15 Tunisian patients from 14 unrelated families. Haplotype analyses and homozygosity mapping with microsatellite markers around known CGD genes assigned the genetic defect to NCF1 in four patients, to NCF2 in four patients and to CYBA in two patients. However, one family with two CGD patients seemed not to link the genetic defect to any known AR-CGD genes. Mutation screening identified two novel mutations in NCF2 and CYBA in addition to the recurrent mutation, DeltaGT, in NCF1 and a splice site mutation previously reported in a North African patient. Our results revealed the genetic and mutational heterogeneity of the AR recessive form of CGD in Tunisia.

Base Sequence↗
PubMed2006

Clinical and mutational investigations of tyrosinemia type II in Northern Tunisia: identification and structural characterization of two novel TAT mutations.

Tyrosinemia type II or Richner-Hanhart Syndrome (RHS) is an autosomal recessive disorder characterized by keratitis, palmoplantar keratosis, mental retardation, and elevated blood tyrosine levels. The disease is due to a deficiency of hepatic cytosolic tyrosine aminotransferase (TATc), an enzyme involved in the tyrosine catabolic pathway. Because of the high rate of consanguinity this disorder seems to be relatively common among the Arab and Mediterranean populations. RHS is characterized by inter and intrafamilial phenotypic variability. A large spectrum of mutations within TATc gene has been shown to be responsible for RHS. In the present study, we report the clinical features and the molecular investigation of RHS in three unrelated consanguineous Tunisian families including 7 patients with confirmed biochemical diagnosis of tyrosinemia type II. Mutation analyses were performed and two novel missense mutations were identified (C151Y) and (L273P) within exon 5 and exon 8, respectively. The 3D-structural characterization of these mutations provides evidence of defective folding of the mutant proteins, and likely alteration of the enzymatic activity. Phenotype variability was observed even among individuals sharing the same pathogenic mutation.

Adult↗
PubMed2005

[Association study between diabetic retinopathy and aldose reductase gene polymorphism in Tunisians].

INTRODUCTION: Aldose reductase (ALR2), the enzyme of the polyol pathway, may play an important role in the pathogenesis of diabetic microvascular complications, namely diabetic retinopathy. The study aimed to determine whether the aldose reductase gene is involved in diabetic retinopathy in the Tunisian population. MATERIAL: and methods: A case-control study was conducted in 47 type 2 diabetic patients who have diabetic retinopathy and 28 diabetic patients without diabetic retinopathy in spite of diabetes lasting for more than 5 years and over 10 years in 13 cases. We investigated the association between the (CA)n polymorphism located at 2.1 kb upstream of the transcription start site of ALR2 and diabetic retinopathy. The distribution of genotypes and alleles was compared between cases and controls by chi2 test using Epi info software. RESULTS: Genotyping of the two groups did not demonstrate any association between the alleles of this marker and diabetic retinopathy in the Tunisian population studied. DISCUSSION: An association between one of the alleles (Z - 2) of this microsatellite and diabetic retinopathy was identified in Chinese and Japanese patients with type 2 diabetes. Discordant results were obtained for the different populations studied. The lack of an association between diabetic retinopathy and ALR2 alleles indicates that the ALR2 gene is not a genetic marker of predisposition to diabetic retinopathy for type 2 diabetic patients in the Tunisian population studied.

Aldehyde Reductase↗
PubMed2003

A novel missense mutation in the gene encoding SLURP-1 in patients with Mal de Meleda from northern Tunisia.

BACKGROUND: Mal de Meleda (MDM) is a rare autosomal recessive skin disorder which belongs to the clinically and genetically heterogeneous group of palmoplantar keratodermas (PPK). Clinically, MDM is characterized by erythema and hyperkeratosis of the palms and soles with sharp demarcation that appears soon after birth and progressively extends to the dorsal surface of the hands and feet. OBJECTIVES: Except for the molecular study reported in Algerian families, MDM has not yet been investigated in the Maghrebian population, characterized by its heterogeneous ethnic background and a high rate of consanguinity. In this study we report genetic and molecular investigations of eight unrelated consanguineous Tunisian families including 17 affected individuals. METHODS: Eight large consanguineous MDM families who originated from cities of northern Tunisia, with a total of 17 patients and 22 unaffected family members were investigated. Families were genotyped with the following microsatellite markers: CNG003, D8S1751 and D8S1836. Mutation analyses were performed in affected patients, in both parents and in unaffected individuals. Linkage analysis was also performed. RESULTS: All the clinical features of MDM were constantly present. Nevertheless variable severity was noted among patients. Histological details were recorded. The haplotype analysis of markers CNG003, D8S1751 and D8S1836 revealed that all affected offspring were homozygous by descent for the three polymorphic markers. The maximum lod score value, 3.22, confirmed the evidence for linkage to the ARS gene. Three haplotypes were observed, and the findings suggest that at least three different mutations within the ARS gene segregate with these haplotypes. Three different mutations were identified, the 82delT mutation previously described and two novel missense mutations. CONCLUSIONS: The results suggest that the ARS gene is likely to be responsible for MDM in the eight Tunisian families. The clinical variability in the expression of PPK in MDM Tunisian patients might be accounted for by the intervention of modifier genes influencing the MDM phenotype.

Antigens, Ly↗
PubMed2002

[Neurologic manifestations of Behcet's disease: analysis of a series of 27 patients].

PURPOSE: To describe epidemiological and clinical characteristics of neurological involvement in Behçet's disease (BD) and to determine a subgroup of patients at high risk for this complication. PATIENTS AND METHODS: The medical notes of 105 patients with BD fulfilling the criteria of the international Study Group for Behçet's disease were retrospectively reviewed. Patients were divided into two groups according to the presence (group 1) or not (group 2) of neurological and/or psychiatric involvement attributable to BD. The epidemiological, clinical and genetic (HLA B51 and MICA 6 frequency) features in the two groups were analysed and compared using the Kruskall-Wallis and the chi-square tests. RESULTS: Twenty-seven patients (25.7%) had clinical evidence of neurological involvement. They were 20 men and 7 women. The mean age at neurological onset was 34.26 +/- 8.79 years. Nineteen patients (70.3%) had meningoparenchymal "MP" central nervous system involvement (brainstem: 9, hemispheric involvement: 6, spinal cord: 4, psychiatric involvement: 2, isolated pyramidal signs: 1, aseptic meningitis: 1). Seven patients (25.9%) had cerebral large vessels involvement that is cerebral angio-Behçet "CAB" (intracranial hypertension: 5 cases due to cerebral venous thrombosis: 3 and pseudotumor cerebri: 2, cerebral haemorrhage: 1, cerebral arterial thrombosis: 1). One patient (3.7%) had both "MP" and "CAB" involvement. Headache was significantly more frequent in non-parenchymal patients. In group 1, complete recovery or improvement with mild neurological impairment was seen in 13 cases, improvement with severe disability in 3 cases, worsening in 1 case, the course was stationary in 1 case and 3 patients died (11.2%). Arterial aneurysms were significantly more frequent in "CAB" subgroups than in subgroup 2. CONCLUSION: Frequency of neurological involvements in BD was high in our study. Arterial aneurysms seem to be a risk factor to these complications. Cerebral angio-Behçet appears to be a protector factor against uveitis.

Adult↗
PubMed2000

Genomic structure and characterisation of the promoter region of the human IL-18 gene.

Interleukin (IL)-18 is a cytokine that plays an important role in the T helper (Th) 1 response, primarily by its ability to induce gamma interferon (IFN-gamma) production by T cells and Natural Killer (NK) cells. It also plays a role in host resistance to infection and in Lipopolysaccharides (LPS)-induced histopathology. By a direct sequencing on P1 Artificial Chromosomes (PAC) clones, we have determined the genomic structure and the promoter region of the human IL-18 gene. The IL-18 gene spans approximately 20 Kb and consists of 6 exous. The 5'-flanking regions of human IL-18 and mouse IL-18 show 75% homology suggesting conserved promoter regulatory factors.

Animals↗
PubMed1997

A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family.

A candidate gene for Branchio-Oto-Renal (BOR) syndrome was identified at chromosome 8q13.3 by positional cloning and shown to underlie the disease. This gene is a human homologue of the Drosophila eyes absent gene (eya), and was therefore called EYA1. A highly conserved 271-amino acid C-terminal region was also found in the products of two other human genes (EYA2 and EYA3), demonstrating the existence of a novel gene family. The expression pattern of the murine EYA1 orthologue, Eya1, suggests a role in the development of all components of the inner ear, from the emergence of the otic placode. In the developing kidney, the expression pattern is indicative of a role for Eya1 in the metanephric cells surrounding the 'just-divided' ureteric branches.

Adult↗
PubMed1997

Clustering of mutations responsible for branchio-oto-renal (BOR) syndrome in the eyes absent homologous region (eyaHR) of EYA1.

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder, characterised by the association of branchial, otic and renal anomalies with variable degrees of severity. We have recently identified EYA1 , a human homologue of the Drosophila eyes absent gene, as the gene underlying this syndrome. The products of both genes share a highly conserved 271 amino acid C-terminal region (eyaHR). The eyaHR was also found in the products of two other human genes (EYA2 and EYA3), demonstrating the existence of a novel gene family. We report here on the complete genomic structure of EYA1. This gene consists of 16 coding exons and extends over 156 kb. It encodes various alternatively spliced transcripts differing only in their 5' regions. Sequence analysis of the entire EYA1 coding region was performed for 20 unrelated patients affected by BOR syndrome, and six novel mutations were identified. Among these mutations, two are missense mutations, highlighting amino acid residues essential for the function of the EYA1 protein, and one mutation comprises a de novo Alu insertion into an exon. This insertion presumably occurs by retrotransposition, and the mobile Alu element has a poly(A) tail that is unstable throughout generations. To date, 14 mutations have been detected in BOR patients, all of which are different. However, all the mutations are located within or in the immediate vicinity of the eyaHR; the significance of this clustering is discussed.

Amino Acid Sequence↗
PubMed1996

Characterization of a translocation-associated deletion defines the candidate region for the gene responsible for branchio-oto-renal syndrome.

Fluorescence in situ hybridization analysis of an 8q translocation breakpoint, dir ins(8)(q24.11;q13.3;q21.13), carried by an individual presenting with Branchio-Oto-Renal (BOR) syndrome, resulted in the identification of an associated deletion. The generation of a YAC contig and the isolation of overlapping recombinant P1 and lambda phage clones from the region allowed further characterization of this deletion. Its size was estimated to be between 470 and 650 kb, and it was flanked by the two polymorphic markers D8S1060 and D8S1807. This mapping led us to reevaluate the localization of the gene responsible for BOR syndrome and has now focused the search for the BOR gene to within the limits of this deletion.

Abnormalities, Multiple↗
PubMed1995

Recombinant BCG expressing the leishmania surface antigen Gp63 induces protective immunity against Leishmania major infection in BALB/c mice.

We have cloned and expressed the gp63 gene of Leishmania major in BCG to develop a recombinant vaccine against zoonotic cutaneous leishmaniasis. Two different expression systems were investigated. The first system consists of pAN, a Mycobacterium paratuberculosis promoter, which drives expression of ORF2, an open reading frame in IS900. This system allows the production of heterologous polypeptides as hybrids with the ORF2 gene product. The second expression system relies on the production of antigenic fragments as fusion proteins with the N-terminal region of Mycobacterium fortuitum beta-lactamase. Both constructs resulted in the production of Gp63 in BCG. The ability of the two recombinant BCG strains to induce protective immunity against a challenge with L. major amastigotes was evaluated after vaccination of susceptible (BALB/c), and resistant (C57BL/6) mice. Recombinant BCG producing Gp63 as a hybrid protein with the N-terminal region of the beta-lactamase elicited significant protection against a challenge with L. major in BALB/c-immunized mice.

Animals↗
PubMed1993

Refined linkage map of chromosome 5 in the region of the spinal muscular atrophy gene.

The genetic map in the region of human chromosome 5 that harbors the gene for autosomal recessive forms of spinal muscular atrophy (SMA) has been refined by a multilocus linkage study in 50 SMA-segregating families. Among six markers spanning 8 cM for combined sexes, four were shown to be tightly linked to the SMA locus. Multipoint linkage analysis was used to establish the best estimate of the SMA gene location. Our data suggest that the most likely location for the SMA locus is between blocks AFM114ye7 (D5S465)/EF5.15 (D5S125) and MAP-1B/JK53 (D5S112) at a sex-combined genetic distance of 2.4 and 1.7 cM, respectively. Thus the SMA gene lies in the 4-cM region between these two blocks. This information is of primary importance for designing strategies for isolating the SMA gene.

Base Sequence↗