Molecular diagnosis of distal renal tubular acidosis in Tunisian patients: proposed algorithm for Northern Africa populations for the ATP6V1B1, ATP6V0A4 and SCL4A1 genes

Background: Primary distal renal tubular acidosis (dRTA) caused by mutations in the genes that codify for the H+ -ATPase pump subunits is a heterogeneous disease with a poor phenotype-genotype correlation. Up to now, large cohorts of dRTA Tunisian patients have not been analyzed, and molecular defects may differ from those described in other ethnicities. We aim to identify molecular defects present in the ATP6V1B1, ATP6V0A4 and SLC4A1 genes in a Tunisian cohort, according to the following algorithm: first, ATP6V1B1 gene analysis in dRTA patients with sensorineural hearing loss (SNHL) or unknown hearing status. Afterwards, ATP6V0A4 gene study in dRTA patients with normal hearing, and in those without any structural mutation in the ATP6V1B1 gene despite presenting SNHL. Finally, analysis of the SLC4A1 gene in those patients with a negative result for the previous studies. Methods: 25 children (19 boys) with dRTA from 20 families of Tunisian origin were studied. DNAs were extracted by the standard phenol/chloroform method. Molecular analysis was performed by PCR amplification and direct sequencing. Results: In the index cases, ATP6V1B1 gene screening resulted in a mutation detection rate of 81.25%, which increased up to 95% after ATP6V0A4 gene analysis. Three ATP6V1B1 mutations were observed: one frameshift mutation (c.1155dupC; p.Ile386fs), in exon 12; a G to C single nucleotide substitution, on the acceptor splicing site (c.175-1G > C; p.?) in intron 2, and one novel missense mutation (c. 1102G > A; p. Glu368Lys), in exon 11. We also report four mutations in the ATP6V0A4 gene: one single nucleotide deletion in exon 13 (c.1221delG; p. Met408Cysfs* 10); the nonsense c.16C > T; p.Arg6*, in exon 3; and the missense changes c.1739 T > C; p.Met580Thr, in exon 17 and c.2035G > T; p.Asp679Tyr, in exon 19. Conclusion: Molecular diagnosis of ATP6V1B1 and ATP6V0A4 genes was performed in a large Tunisian cohort with dRTA. We identified three different ATP6V1B1 and four different ATP6V0A4 mutations in 25 Tunisian children. One of them, c.1102G > A; p.Glu368Lys in the ATP6V1B1 gene, had not previously been described. Among deaf since childhood patients, 75% had the ATP6V1B1 gene c. 1155dupC mutation in homozygosis. Based on the results, we propose a new diagnostic strategy to facilitate the genetic testing in North Africans with dRTA and SNHL.This research study was supported by PI09/90888 and PI11/01412 grants, from the Instituto de Salud Carlos III (Spain), by BIO08/ER/020 grant, from the EITB Maratoia-Bioef (Basque Foundation for Health Innovation and Research) and by the Tunisian Ministry of Scientific Research (Research Unit code 05/UR-09-04, University of Monastir) for DEH mobility

Microbial Exopolysaccharides as Alternative Sources of Dietary Fibers with Interesting Functional and Healthy Properties

Traditional polysaccharides obtained from plants may suffer from a lack of reproducibility in their rheological properties, purity, supply and cost. Most of the used plant polysaccharides are chemically modified to improve their characteristics. Microbial exopolysaccharides (EPSs) are principally composed of carbohydrate polymers, and they are produced by many microorganisms including bacteria, yeasts and fungi. Microorganisms can synthesize EPSs and excrete them out of cell either as soluble or insoluble polymers. These EPSs are able not only to protect the microorganisms themselves against desiccation, phage attack, antibiotics or toxic compounds, but also can be applied in several biotechnological applications. In food products they increase the dietary fiber content and can be used as viscosifiers, stabilizers, emulsifiers or gelling agents to improve physical and structural properties of water and oil holding capacity, viscosity, texture, sensory characteristics and shelf-life. EPSs are used as additives in various foods, such as dairy products, jams and jellies, wine and beer, fishery and meat products, icings and glazes, frozen foods and bakery products. Over the past few decades, interest in using microbial EPSs in food processing has been increasing because of main reasons such as easy production, better rheological and stability characteristics, cost effectiveness and supply. Dextran, xanthan, pullulan, curdlan, levan and gellan and alginate are the main examples of industrially important microbial exopolysaccharides. They also play crucial role in conferring beneficial physiological effects on human health, such as the ability to lower pressure and to reduce lipid level in blood. Furthermore, these EPSs exhibit antitumor, immunomodulating, antioxidant and antibacterial properties. The utility of various biopolymers are dependent on their monosaccharide composition, type of linkages present, degree of branching and molecular weight. In the present chapter, an attempt was taken to recapitulate the most important polysaccharides isolated from microorganisms as well as the main methods for microbial exopolysaccharide production, purification and structural characterization. In addition, the functional and healthy benefits of EPSs and their applications in food industry were described

Detection and Genomic Characterization of Aichi Viruses in Stool Samples from Children in Monastir, Tunisia▿

Aichi virus has been associated with acute gastroenteritis in adults and children. Stool samples were collected from 788 Tunisian children suffering from diarrhea. Aichi virus was found in 4.1% of the cases. The high proportion of monoinfections and the high frequency of hospitalizations support the role of Aichi virus in pediatric gastroenteritis

Molecular epidemiology of human astrovirus and adenovirus serotypes 40/41 strains related to acute diarrhea in Tunisian children.

International audienceHuman astrovirus (AstV) and adenovirus types 40 and 41 (AdV 40/41) are responsible for epidemic and endemic acute gastroenteritis in children and adults. The present study was designed to evaluate the prevalence and genetic diversity of enteric viruses in children in Tunisia. A total of 788 fecal samples were collected during a 4-year period in the region of Monastir, from children under 12 years old, hospitalized or presenting in dispensaries with symptoms of acute gastroenteritis. AstV and AdV40/41 were detected by immunoenzymatic methods and confirmed by PCR/RT-PCR and sequence analysis. Phylogenetic analyses were performed for nucleotide homology with reference strains. AstV and AdV40/41 were characterized as a causative agent in 28 (3.6%) and 18 (2.3%) of the fecal samples, respectively. Phylogenetic analysis showed that the AstVs belonged to the serotypes 3 (n = 4; 14.3%) and 1 (n = 24; 85.7%), and the enteric AdVs to the serotypes 40 (n = 1; 5.6%) and 41 (n = 17; 94.4%). This is the first report that describes the molecular epidemiology of AstV and AdV40/41 in Tunisian children. Their respective detection rate was very low, far below that of rotavirus and norovirus. The genetic diversity among these two viruses is relatively limited and varies depending on the area