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Biomedical subjects

H Ayadi

Publications and source records attributed to H Ayadi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cloning and characterization of SLC26A6, a novel member of the solute carrier 26 gene family.

The SLC26 gene family (solute carrier family 26) comprises five mammalian genes that encode anion transporter-related proteins. In addition to sat-1 and prestin, which were cloned from rat and gerbil, respectively, three human members have been identified and associated with specific genetic diseases (DTD, diastrophic dysplasia; CLD, congenital chloride diarrhea; PDS, Pendred syndrome). In this study we used a homology approach combined with RACE PCR to identify human SLC26A6, the sixth member of this gene family. Northern blot analysis showed the highest SLC26A6 transcript levels in kidney and pancreas. Expression in MDCK cells and in Xenopus oocytes demonstrated trafficking of the SLC26A6 protein to the cell membrane but did not reveal anion transport activity with tracer uptake or intracellular pH measurements. We determined the genomic structure of the SLC26A6 gene and excluded mutations in the 21 coding exons as the cause of DFNB6 and USH2B, which closely map to the SLC26A6 chromosomal locus (3p21).

Amino Acid Sequence↗
PubMed2001

Novel missense mutations of TMPRSS3 in two consanguineous Tunisian families with non-syndromic autosomal recessive deafness.

Recently the TMPRSS3 gene, which encodes a transmembrane serine protease, was found to be responsible for two non-syndromic recessive deafness loci located on human chromosome 21q22.3, DFNB8 and DFNB10. We found evidence for linkage to the DFNB8/10 locus in two unrelated consanguineous Tunisian families segregating congenital autosomal recessive sensorineural deafness. The audiometric tests showed a loss of hearing greater than 70 dB, in all affected individuals of both families. Mutation screening of TMPRSS3 revealed two novel missense mutations, W251C and P404L, altering highly conserved amino acids of the serine protease domain. Both mutations were not found in 200 control Tunisian chromosomes. The detection of naturally-occurring TMPRSS3 missense mutations in deafness families identifies functionally important amino acids. Comparative protein modeling of the TMPRSS3 protease domain predicted that W251C might lead to a structural rearrangement affecting the active site H257 and that P404L might alter the geometry of the active site loop and therefore affect the serine protease activity.

Amino Acid Sequence↗
PubMed2001

CTLA-4 gene polymorphisms in Tunisian patients with Graves' disease.

Graves' disease (GD) is an organ-specific autoimmune disorder of multifactorial etiology with a polygenic mode of inheritance. A recent report has demonstrated that there is a linkage and an association between the genetic markers of the CTLA-4 gene on chromosome 2q33 and GD. In order to confirm this association in a Tunisian population, three polymorphisms of the CTLA-4 gene were analyzed: the first is at the -318 position from the ATG start codon consisting of a C/T change; the second is in position 49 of exon 1, which lies in the A/G transition; and the third is in the 3' untranslated region with variant lengths of the dinucleotide (AT)n repeat. The genomic DNA from 144 patients with GD and 205 healthy individuals was genotyped after specific polymerase chain reaction amplification. Comparative analysis using a chi(2) test showed a weak yet significant difference in allele frequencies of the A/G dimorphic marker between patients and controls (P < 0.05), and a significant increase of A/A homozygous individuals among patients (21.53 vs 12.7%, P = 0.02, odds ratio (OR) = 1.89) was found. Analyses of CTLA-4 A/G polymorphism with respect to sex showed a significant difference in A/A genotypes between female patients and controls (OR = 2.14; 95%, 1.13 < OR < 4.04, P < 0.05). The distribution of CTLA-4 (AT)n allele frequencies differed between patients and controls (chi(2) = 38.18, 20 degrees of freedom, P = 0.0084) and the highest OR was found with the CTLA-4 (AT)-224-bp allele (OR = 6.43, 1.7 < OR < 28.64; P = 0.001). In conclusion, these results show that the CTLA-4 gene, or one closely associated with it, confers susceptibility to GD in a Tunisian population.

Abatacept↗
PubMed2001

Inhibition of potato virus Y NIa activity: preparation of monoclonal antibody directed against PVY NI protein that inhibits cleavage of PVY polyprotein.

A partially purified nuclear inclusion (NI) fraction was obtained from tobacco plants infected by potato virus Y (PVY). Four monoclonal antibodies (MAbs) were produced and characterized using this semipurified fraction as antigen. Data showed that only one was directed against NIa whereas two were directed against cytoplasmic inclusion (CI) protein and the last one against coat protein (CP). These results were due to the fact that the semipurified NI fraction was usually contaminated with CI and CP proteins. When used on in situ immunofluorescence method the anti-NIa MAb showed accumulation of the NIa protein in both nucleus and cytoplasm. In vivo, this MAb was able to detect different forms of the NIa protein including precursors and cleavage products. It was also able to inhibit the cleavage of the polyprotein detected in the semipurified NI.

Animals↗
PubMed2001

Lack of linkage and association between autoimmune thyroid diseases and the CTLA-4 gene in a large Tunisian family.

The autoimmune thyroid diseases (AITDs) including Graves' disease and Hashimoto's thyroiditis are inherited as complex traits. We have performed linkage and association studies to investigate the role of CTLA-4 gene in the AITDs development using the D2S311, D2S143, the intragenic CTLA-4 (AT)(n) microsatellite markers and the CTLA-4 (A/G) dimorphism in exon 1. Four extended pedigrees belonging to a large Tunisian family named Akr and including 154 individuals from which 20 were affected with Hashimoto's thyroiditis and 26 with Graves' disease, were used in this investigation. No evidence for linkage with none of the markers was found under neither dominant nor recessive models [Z=-7.14 and Z=-14.32 at theta=0.0, respectively for the CTLA-4 (AT)(n) marker]. A family-based association study on 51 nuclear families derived from the Akr pedigree was performed by the FBAT approach applied to the CTLA-4 (AT)(n) marker and the CTLA-4 (A/G) dimorphism. We found no association of individual alleles to disease for both markers. These results showed no evidence for the involvement of the CTLA-4 locus in the AITDs pathogenesis.

Abatacept↗
PubMed2001

A full genome screening in a large Tunisian family affected with thyroid autoimmune disorders.

The autoimmune thyroid diseases (AITDs) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are inherited as complex traits. We initiated a whole genome linkage study of patients with AITD, in order to identify the susceptibility genes involved in their pathogenesis. We studied 39 patients affected with GD or HT and 68 related controls, who belonged to a large consanguinous family composed of more than 200 members. Linkage analysis was performed using the lod score method under two arbitrary models, one dominant and one recessive. A positive lod score was found for D2S171, assuming a recessive mode of inheritance and 50% penetrance, which suggests the presence of a major AITD susceptibility gene on chromosome 2p21. However, no linkage was found with microsatellite markers spanning the HLA system. This locus localised outside MHC will be of interest for investigation of other autoimmune disorders.

Adolescent↗
PubMed2001

HLA-DQB1 CAR1/CAR2, TNFa IR2/IR4 and CTLA-4 polymorphisms in Tunisian patients with rheumatoid arthritis and Sjögren's syndrome.

OBJECTIVES: To evaluate the contribution of HLA class II region and the CTLA-4 gene in genetic susceptibility to rheumatoid arthritis (RA) and Sjögren's syndrome (SS) in the Tunisian population. METHODS: The polymorphisms of a (CA)n microsatellite of HLA-DQB1 CAR1/CAR2, TNFa IR2/IR4 and an (AT)n microsatellite in the 3'-untranslated region of exon 3 of the CTLA-4 gene were analysed after specific polymerase chain reaction (PCR) amplification. Typing of CTLA-4 A/G exon 1 polymorphism was achieved by the PCR-restriction fragment length polymorphism method. RESULTS: Genomic DNA from 60 patients with RA, 58 patients with SS and 150 healthy individuals was genotyped. The distribution of HLA-DQ CAR1/CAR2 allele frequencies differed between patients and controls in both diseases (RA, P<10(-15); SS, P=7.6x10(-15); RA+SS, P<10(-15)). The analysis of TNFa IR2/IR4 and CTLA-4 A/G polymorphisms did not show any differences in allele or genotype frequencies between patients and control subjects in either disease. The distribution of CTLA-4 (AT)n allele frequencies differed between patients with RA and controls (P=10(-3)), whereas no significant difference was detected between patients with SS and controls. CONCLUSION: These data suggest the involvement of HLA-DQ CAR1/CAR2 polymorphisms in genetic susceptibility to RA and SS and the participation of the CTLA-4 gene, or a gene closely associated with it, in the development of RA.

Abatacept↗
PubMed2001

[Localized tracheobronchial amyloidosis: a rare cause of pseudo-asthma].

Localized tracheobronchial amyloidosis is an uncommon disease of unknown cause. Bronchial amyloid deposits can occur as focal nodules or multifocal infiltration of the submucosa. Clinical signs are not specific and the chest x-ray is usually normal. Diagnosis is rarely evoked before bronchial biopsies are done. We report a case of tracheobronchial amyloidosis disclosed by asthmatiform dyspnea. The diagnosis was obtained at bronchial fibroscopy performed as part of the work-up for secondary pneumonia.

Aged↗
PubMed2000

Pendred syndrome: phenotypic variability in two families carrying the same PDS missense mutation.

Pendred syndrome comprises congenital sensorineural hearing loss, thyroid goiter, and positive perchlorate discharge test. Recently, this autosomal recessive disorder was shown to be caused by mutations in the PDS gene, which encodes an anion transporter called pendrin. Molecular analysis of the PDS gene was performed in two consanguineous large families from Southern Tunisia comprising a total of 23 individuals affected with profound congenital deafness; the same missense mutation, L445W, was identified in all affected individuals. A widened vestibular aqueduct was found in all patients who underwent computed tomography (CT) scan exploration of the inner ear. In contrast, goiter was present in only 11 affected individuals, who interestingly had a normal result of the perchlorate discharge test whenever performed. The present results question the sensitivity of the perchlorate test for the diagnosis of Pendred syndrome and support the use of a molecular analysis of the PDS gene in the assessment of individuals with severe to profound congenital hearing loss associated with inner ear morphological anomaly even in the absence of a thyroid goiter.

Adolescent↗
PubMed2000

Polymorphisms of HLA DQB1 CAR1/CAR2 and TNFalpha IR2/IR4 microsatellite markers in patients affected with Graves disease.

Graves disease is an autoimmune thyroid disorder in which HLA class I and II confer susceptibility in different ethnic groups. An allele-specific polymerase chain reaction was used to characterize the variation of the HLA-DQB1 CAR1/CAR2 and TNFalpha markers located on chromosome 6 in 85 unrelated Tunisian patients affected with Graves disease and 148 healthy control subjects. In contrast to the results regarding TNFalpha alleles showing no difference between patients and controls (P = 0.904), the analysis of the HLA-DQB1 CAR1/CAR2 polymorphism showed a significant difference in its alleles (P < 0.0001). Nevertheless, no allele exhibited a predispositional effect on GD pathogenesis.

Alleles↗
PubMed2000

Mutations of GJB2 in three geographic isolates from northern Tunisia: evidence for genetic heterogeneity within isolates.

Geographically isolated populations have been successfully used to localize genes for recessive inherited diseases, including non-syndromic sensorineural recessive deafness (NSRD). To date, 25 loci for NSRD have been localized on human chromosomes (DFNB loci), and six of the corresponding genes have been identified. Here, we report on the contribution of the DFNB1 locus (GJB2 gene) to NRSD in seven affected families living in three northern Tunisian geographic isolates, and we provide evidence for genetic heterogeneity within isolates. This finding challenges the classical view of a single 'founder' mutation segregating in such isolates.

Alleles↗
PubMed2000

[Dry cough in a 17 year old patient].

We present a case of mediastinal ganglioneuroma observed in a 17-year-old girl. Imaging suggested the diagnosis that was confirmed histologically on a peroperative specimen. Mediastinal ganglioneuroma is a highly uncommon tumor with characteristic imaging features that is quite difficult to resect.

Adolescent↗
PubMed2000

Deafness genes and the mechanism of hearing.

Over the past few years, significant progress has been made in the understanding of the hearing mechanism. The identification of genes involved in deafness has begun and is now progressing rapidly. To date, at least 36 genes are known and exploration of their functions has already begun. Indeed, cloning deafness genes is only the first step towards the understanding of the hearing process.

Deafness↗