Non-classical human leukocyte antigen class I in Tunisian children with autism.

Autism spectrum disorders (ASD) are one of the most common childhood morbidities characterized by deficits in communication and social skills. Increasing evidence has suggested associations between immune genes located in the human leukocyte antigen (HLA) complex and etiology of autism. In this study, we investigated whether the non-classical class I HLA-G, -E, and -F polymorphisms are associated with genetic predisposition to autism in Tunisia. We aimed to find a correlation between HLA-G genotypes and soluble HLA-G (sHLA-G) levels. We have analyzed the HLA-G, -E, and -F genotypes of 15 autistic children and their parents. DNA typing of HLA class I genes was performed using PCR-SSP and PCR-RFLP methods. Also, we evaluated the serum levels of HLA-G (1 and 5) by a validated ELISA technique in autistic probands and their parents. No association was found between any polymorphism and autism in the study subjects. Additionally, we found no correlation between sHLA-G1 and sHLA-G5 and autism. Also, no significant difference in sHLA-G testing in parents and offspring was found. However, parents carrying [GG] genotype presented a higher sHLA-G levels than those carrying ([CC]+[GC]) genotypes (p = 0.037). From this preliminary study, we conclude that the investigated polymorphisms of HLA-G, -E, and -F genes did not lead to autism susceptibility in Tunisian children. However, the CGTIGA haplotype was found to be associated with the disease.

Identity-by-descent-guided mutation analysis and exome sequencing in consanguineous families reveals unusual clinical and molecular findings in retinal dystrophy.

PURPOSE: Autosomal recessive retinal dystrophies are clinically and genetically heterogeneous, which hampers molecular diagnosis. We evaluated identity-by-descent-guided Sanger sequencing or whole-exome sequencing in 26 families with nonsyndromic (19) or syndromic (7) autosomal recessive retinal dystrophies to identify disease-causing mutations. METHODS: Patients underwent genome-wide identity-by-descent mapping followed by Sanger sequencing (16) or whole-exome sequencing (10). Whole-exome sequencing data were filtered against identity-by-descent regions and known retinal dystrophy genes. The medical history was reviewed in mutation-positive families. RESULTS: We identified mutations in 14 known retinal dystrophy genes in 20/26 (77%) families: ABCA4, CERKL, CLN3, CNNM4, C2orf71, IQCB1, LRAT, MERTK, NMNAT1, PCDH15, PDE6B, RDH12, RPGRIP1, and USH2A. Whole-exome sequencing in single individuals revealed mutations in either the largest or smaller identity-by-descent regions, and a compound heterozygous genotype in NMNAT1. Moreover, a novel deletion was found in PCDH15. In addition, we identified mutations in CLN3, CNNM4, and IQCB1 in patients initially diagnosed with nonsyndromic retinal dystrophies. CONCLUSION: Our study emphasized that identity-by-descent-guided mutation analysis and/or whole-exome sequencing are powerful tools for the molecular diagnosis of retinal dystrophy. Our approach uncovered unusual molecular findings and unmasked syndromic retinal dystrophies, guiding future medical management. Finally, elucidating ABCA4, LRAT, and MERTK mutations offers potential gene-specific therapeutic perspectives.

Prevalence of self-reported food allergy in Tunisia: General trends and probabilistic modeling.

Background: Food allergy (FA) has become a major public health concern affecting millions of children and adults worldwide. In Tunisia, published data on FA are scarce. Methods: This study, was intended to fill the gap and estimate the frequency of allergy to different foods in the Sfax region, Tunisia, within self-reported FA. One hundred twenty-five (125) children (56% males, 1-17 years old), and 306 adults (17% males, 18-70 years old) were interviewed using a bilingual questionnaire. Results: The number of self-reported food allergens in this sample was 105; allergens were clustered in 8 foods: fruits, seafood, eggs, milk and dairy, cereals, nuts, vegetables, and peanuts. Cutaneous reactions were the most frequent symptoms, in both children and adults. About 40% of children and 30% of adults had a family history of FA. About 81% of adults and 38% of children are allergic to at least 1 non-food allergen. The most prevalent food allergen was the fruit group in both adults and children, followed by seafood. Most food allergies were mutually exclusive and 90% of individuals have a single FA. The relationship between self-declared FA was modeled using a Bayesian network graphical model in order to estimate conditional probabilities of each FA when other FA is present. Conclusions: Our findings suggest that the prevalence of self-reported FA in Tunisia depends on dietary habits and food availability since the most frequent allergens are from foods that are highly consumed by the Tunisian population.

Effect of subchronic exposure to tetradifon on bone remodelling and metabolism in female rat.

This study investigates the effect of subchronic exposure to tetradifon, an organochlorine pesticide with an oestrogen-like structure, in female rat. A single cumulative dose of 2430 mg/kg BW was administrated orally for 12 female rats of 190 g BW. Twelve non-treated additional rats have served as controls. Animals were sacrificed after 6 and 12 weeks of treatment. We studied bone remodelling through histomorphometry and scanning electron microscopy (SEM) analyses. The serum and the right femora were used to determine phosphatase alkaline (AlkP) and/or calcium and phosphorus content. No sign of toxicity was observed until the end of the experiment. The SEM results revealed no structural alteration of the treated animal bone tissue. However, in both treated groups, we have noted an increase in the trabecular distance and a heterogeneous aspect of the endosteum that could be explained by bone-remodelling disturbance, with relative delay of ossification. Following histomorphomotric analysis, these results were coupled with significant increases in Tb.Th and OS/BS. Elsewhere, tetradifon intoxication increased significant serum AlkP level in the group treated for 12 weeks, which could be explained by an osteoblastic hyperactivity. Tetradifon intoxication decreased significantly bone calcium end phosphorus contents. Tetradifon seems not to exert major effects on bone remodelling. However, the osteoblastic hyperactivity could be explained by the oestrogen-like activity of tetradifon and its fatty metabolism. In fact, oestrogen inhibits bone remodelling, and enhances bone formation, which could result in an increase of the osteoid surface and explain the relative delay of ossification.

Nonclassical human leukocyte antigen (HLA-G, HLA-E, and HLA-F) in coronary artery disease.

AIMS: Several evidences suggest the association between the evolution of coronary artery disease (CAD) and the development of coronary syndrome that is often associated with disrupted plaque and partial or complete thrombosis of the related artery. Because of the inflammatory nature of CAD, we investigated the human leukocyte antigen (HLA)-G, HLA-E, and HLA-F genetic polymorphisms within CAD patients and evaluated their potential association with this disease in Tunisian population. METHODS: Different polymorphisms in HLA-G (14-bp Insertion/Deletion, +3142C/G), HLA-E (HLA-E*01:01/01:03 A/G), HLA-F (HLA-F*01:02 T/C, 01:03 C/T, 01:04 A/C) genes were typed using different laboratory techniques in a cohort of 89 CAD patients and 84 controls. RESULTS: A significant association was reported between the HLA-G +3142 G allele (OR=1.64, 95% CI=1.05-2.56, p=0.02) and increased risk of CAD. No association was found for the other studied polymorphisms. When we considered the haplotypes, we found TDELCA and TDELGG haplotypes associated to CAD with p=0.008 and p=0.030, respectively, suggesting the potential interaction between HLA-G and HLA-E genes. CONCLUSIONS: Our findings indicated that the HLA-G +3142C/G polymorphism and TDELCA and TDELGG haplotypes can harbour a reliable diagnosis value for the risk of CAD development suggesting that HLA-G, -E and -F molecules might be involved in the pathogenesis of the disease. However, further studies are necessary to confirm our results.

Cytogenetics and fluorescence in situ hybridization assessment of sex-chromosome mosaicism in Klinefelter's syndrome.

A retrospective study was carried out in 152 infertile men to determine the prevalence of sex chromosome abnormalities among non-obstructive azoospermic and severe oligospermic men (n = 51) and to evaluate the feasibility of fluorescence in situ hybridization (FISH) techniques to assess mosaicism in Klinefelter's patients in comparison with conventional cytogenetics. Cytogenetic analysis were performed for 51 infertile men and among 14 chromosomal abnormalities found, nine were compatible with Klinefelter's syndrome. FISH staining with a CEP X/CEP Y probes were performed for Klinefelter's patients and for five of them; testes were biopsied for histopathologic examination. Six Klinefelter's patients showed a non-mosaic 47,XXY and three showed a 47,XXY/46,XY mosaic by G or R banding analysis of 20 cells with a ratio of 17%, 20% and 33%, respectively. FISH analysis confirmed mosaicism in only one patient (the first) in whom a third cells population was found. There was no relationship between the ratios of mosaicism by banding and FISH analysis. Conventional histopathologic findings in five non-mosaic Klinefelter's patients confirm the diagnosis of Sertoli Only Cells syndrome. FISH is recommended in Klinefelter's syndrome to define exactly the cytogenetic statute as mosaic or non-mosaic and then discussing prognosis and decision regarding fertility counseling.