[Trisomy 18 or postnatal Edward´s syndrome: descriptive study conducted at the University Hospital Center of Casablanca and literature review]. / La trisomie 18 ou syndrome d'Edwards en post-natal: étude descriptive au Centre Hospitalier Universitaire de Casablanca et revue de littérature.

Trisomy 18 is a chromosomal disease, caused by the presence of a supernumerary chromosome 18. Mortality among infants with trisomy 18 is high, secondary to lethal malformations associated with this syndrome. The purpose of this study was to describe the clinical and cytogenetic features of these patients, as well as the role of genetic counselling. We conducted a cross-sectional descriptive study over a 5-year period, from July 2015 to April 2019. The study involved, patients followed up in the Department of Medical Genetics at the University Hospital Center Ibn Rochd of Casablanca, having abnormalities suggestive of trisomy 18, then confirmed by cytogenetic study. The study enrolled 5 patients, 3 girls and 2 boys (female predominance; sex-ratio = 0,67) with clinically suspected Edward's syndrome, then confirmed by cytogenetic study. The mean age at diagnosis was 37.40 ± 23.98 days (9 days-2 months). Trisomy 18 was clinically suspected in two cases based on facial dysmorphism and malformative syndrome, a recognizable pattern of chromosomal abnormality. Two patients were hospitalized in the intensive care unit for decompensated heart failure associated with congenital heart disease, while one patient had neonatal respiratory distress associated with polymalformative syndrome at diagnosis. Cytogenetic study confirmed the diagnosis of free and homogeneous trisomy 18 in five patients, then genetic counselling was performed. The prevalence of trisomy 18 is variable. Global prevalence is estimated at 1/6000 live births, females are mostly affected. The diagnosis of trisomy 18 should be suspected at birth in newborns with typical craniofacial dysmorphism, arms lifted in supplication and permanent flexion of the fingers, the index finger overlapping the 3rd finger, the little finger overlapping the 4th finger. There are several malformations associated with trisomy 18. This syndrome should be also suspected in the antenatal period in patients with abnormalities on obstetric ultrasound. Moreover, survival is low and only one in 10 newborns reach the first year of life.

The PTPN22 C1858T (R620W) functional polymorphism in inflammatory bowel disease.

OBJECTIVE: In view of the discrepant data regarding the association between the protein tyrosine phosphatase non-receptor 22 (PTPN22) rs2476601 (R620W, 1858C→T) polymorphism and susceptibility to autoimmune diseases including inflammatory bowel diseases (IBD), we investigated whether this functional single-nucleotide polymorphism influences IBD risk in a group of Moroccan patients. RESULTS: This is the first report on the prevalence of PTPN22 (R620W) variant in a Moroccan cohort. No evidence of statistically significant differences was observed when the PTPN22 (R620W) allele and genotype distribution among IBD, Crohn's disease (CD), ulcerative colitis (UC) patients and healthy controls were compared. The frequency of the variant allele in healthy subjects was 1.77% compared to 2.56% in the IBD patients and 1.85% in CD patients. Furthermore, the frequency of this allele was increased in UC patients compared to controls (4.17% vs. 1.77%, OR = 2.42, 95% CI 0.82-7.08; P = 0.09), but the difference was not statistically significant. Our data suggest a lack of association between PTPN22 R620W variant and IBD susceptibility in Moroccan patients.

Polymorphisms in oxidative pathway related genes and susceptibility to inflammatory bowel disease.

AIM: To investigate whether common variants in the oxidative pathway genes influence inflammatory bowel disease (IBD) risk among Moroccan patients. METHODS: The distribution of (TAAA)n_rs12720460 and (CCTTT)n _rs3833912 NOS2A microsatellite repeats, HIF-1A_rs11549467 and NFKB1-94ins/delATTG_rs28362491 was analyzed in 507 subjects grouped in 199 IBD and 308 healthy controls. Genotyping was performed with polymerase chain reaction-fluorescent method and the TaqMan® allelic discrimination technology. RESULTS: The allele and genotype frequencies of HIF1A_ rs11549467, NFKB1_rs28362491 and NOS2A_ (TAAA)n did not differ significantly between patients and controls. Analysis of NOS2A_ (CCTTT)n markers evidenced differences between patients and healthy controls. A preferential presence of the (CCTTT)8 (P = 0.02; OR = 1.71, 95%CI: 1.07-2.74), (CCTTT)14 (P = 0.02; OR = 1.71, 95%CI: 1.06-2.76) alleles in IBD, (CCTTT)8 (P = 0.008; OR = 1.95, 95%CI: 1.17-3.23) in CD and (CCTTT)7 (P = 0.009; OR = 7.61, 95%CI: 1.25-46.08), (CCTTT)11 (P = 0.05; OR = 0.51, 95%CI: 0.25-1.01), (CCTTT)14 (P = 0.02; OR = 2.05, 95%CI: 1.07-3.94), (CCTTT)15 (P = 0.01; OR = 2.25, 95%CI: 1.16-4.35) repeats in UC patients indicated its possible association with higher disease risk which need to be confirmed in a larger sample size. CONCLUSION: Our results suggest that the NOS2A_ (CCTTT)n gene variations may influence IBD susceptibility in the Moroccan population.

Genetic Polymorphisms of Multidrug Resistance Gene-1 (MDR1/ABCB1) and Glutathione S-Transferase Gene and the Risk of Inflammatory Bowel Disease among Moroccan Patients.

Inflammatory bowel diseases (IBD) are multifactorial disorders resulting from environmental and genetic factors. Polymorphisms in MDR1 and GSTs genes might explain individual differences in susceptibility to IBD. We carried out a case-control study to examine the association of MDR1 (C1236T and C3435T), GSTT1, and GSTM1 polymorphisms with the risk of IBD. Subjects were genotyped using PCR-RFLP for MDR1 gene and multiplex PCR for GSTT1 and GSTM1. Meta-analysis was performed to test the association of variant allele carriage with IBD risk. We report that GSTT1 null genotype is significantly associated with the risk of CD (OR: 2.5, CI: 1.2-5, P = 0.013) and UC (OR: 3.5, CI: 1.5-8.5, P = 0.004) and can influence Crohn's disease behavior. The interaction between GSTT1 and GSTM1 genes showed that the combined null genotypes were associated with the risk of UC (OR: 3.1, CI: 1.1-9, P = 0.049). Furthermore, when compared to combined 1236CC/CT genotypes, the 1236TT genotype of MDR1 gene was associated with the risk of UC (OR: 3.7, CI: 1.3-10.7, P = 0.03). Meta-analysis demonstrated significantly higher frequencies of 3435T carriage in IBD patients. Our results show that GSTT1 null and MDR1 polymorphisms could play a role in susceptibility to IBD.

Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms: New data and a meta-analysis.

BACKGROUND: The pathogenesis of inflammatory bowel disease (IBD) involves interactions between the host genetic susceptibility, intestinal microflora and mucosal immune responses through the pattern recognition receptor. Polymorphisms in toll-like receptor 4 (TLR4) induce an aberrant immune response to indigenous intestinal flora, which might favor IBD development. In this study, we aimed to determine whether TLR4 gene was associated with Crohn's disease (CD) and ulcerative colitis (UC) among Moroccan patients, and evaluated its correlation with clinical manifestation of the disease. METHODS: The study population comprised 117 patients with IBD and 112 healthy unrelated blood donors. TLR4 polymorphisms: Asp299Gly and Thr399Ile were genotyped by polymerase chain reaction-restriction fragment length polymorphism. PCR products were cleaved with Nco I for the Asp299Gly polymorphism and Hinf I for the Thr399Ile polymorphism. Meta-analysis was performed to test the association of 299Gly and 399Ileu carriage with CD, UC and the overall IBD risk. RESULTS: Our study revealed that the frequency of Asp299Gly and Thr399Ile did not differ significantly between patients and controls in the Moroccan population. However, meta-analysis demonstrated significantly higher frequencies of both Asp299Gly and Thr399Ile SNPs in IBD and CD and for 399Ileu carriage in UC patients. CONCLUSION: The meta-analysis provides evidence that TLR4 polymorphisms confer a significant increased risk for the overall IBD development.

IL23R and ATG16L1 variants in Moroccan patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel diseases (IBD) are chronic diseases of the gastrointestinal tract. Although their pathogenesis is unclear, the combination of genetic predisposition and environmental components are believed to be the main cause of these diseases. Recently, many variants in interleukin 23 receptor (IL23R) and autophagy-related 16-like 1 (ATG16L1) genes have been associated with the disease. Our objective was to assess the frequency of ATG16L1 (T300A) and IL23R (L310P) variants in Moroccan IBD (Crohn's disease and Ulcerative Colitis) patients and to evaluate a possible effect of these variants on disease's phenotype and clinical course. METHODS: 96 Moroccan IBD patients and 114 unrelated volunteers were genotyped for ATG16L1 (T300A) and IL23R (L310P) variants by PCR-restriction fragment length polymorphism. RESULTS: This is the first report on the prevalence of ATG16L1 (T300A) and IL23R (L310P) variants in a Moroccan group. We found that IL23R (L310P) variant conferred a protective effect for crohn's disease (CD) but not ulcerative colitis (UC) patients. The presence of ATG16L1 (T300A) mutated alleles was associated with CD type but not with disease onset. In addition, the carriage of T300A variant alleles conferred a protective effect in UC. CONCLUSION: Our results showed that the prevalence of ATG16L1 and IL23R variants was not significantly different between patients and controls. However a possible role of ATG16L1 (T300A) on CD phenotype was suggested.

NOD2/CARD15 gene influences disease behaviour but not IBD susceptibility in a Moroccan population.

BACKGROUND/AIMS: IBD (Crohn's disease and Ulcerative Colitis) is chronic and multifactorial disease of the gastrointestinal tract. Till now, his pathogenesis remains unclear. It involves innate immunity, environmental component and genetic predisposition. Polymorphisms in NOD2/CARD15 have been implicated in Crohn's disease in several ethnic groups. The purpose of our study was to assess the frequency of the three major variants of this gene (Leu1007fsinsC, R702W, and G908R) in Moroccan IBD patients and to determine a possible effect of these variants on Disease's phenotype and clinical course. MATERIALS AND METHODS: A total of 96 Moroccan unrelated IBD patients and 114 healthy controls were genotyped (PCR-RFLP method) for the three main polymorphisms. RESULTS: In this study, no correlation was found between NOD2/CARD15 polymorphisms and ulcerative colitis or Crohn's disease in our population. Nevertheless, 3020insC (Leu1007fsinsC) variant was associated to a structuring behaviour on CD patients. CONCLUSION: These findings suggest that NOD2/CARD15 influences disease behaviour but not susceptibility to crohn's disease in Moroccan IBD patients.

Methylenetetrahydrofolate reductase C677T variant in Moroccan patients with inflammatory bowel disease.

BACKGROUND: The association of genetic polymorphisms related to metabolism of homocysteine and folate with inflammatory bowel disease has been evidenced. Several studies have identified genetic variants of MTHFR as significant susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC). The C677T genetic polymorphism in the MTHFR gene is found to be associated with a thermolabile variant enzyme that shows a reduced activity. Therefore, we investigated whether the C677T variant confers genetic susceptibility to CD or UC and evaluated the genotype-phenotype associations in the Moroccan population. METHODS: The present study included 96 inflammatory bowel disease patients (68 patients with CD and 28 with UC) and 182 healthy controls. DNA samples were genotyped for the MTHFR (C677T) mutation by the PCR-RFLP method. Statistical analyzes were performed using MedCalc software, Chi square test and Fisher test. RESULTS: The respective odds ratio for CD, UC and control group were, 1.55 (CI 95%: 0.53-4.53, P=0.52); 0.50 (CI 95%: 0.06-4.15, P=0.52) and 0.50 (CI 95%: 0.06-4.15, P=0.52). Thus, no statistically significant association with the disease was observed in frequency of the TT variant in comparison to healthy controls. Stratification of IBD patients on the basis of CD or UC showed that individuals carrying at least one T allele are not protected against Crohn's disease. Furthermore, clinical features of the disease did not show any significant association. CONCLUSION: In conclusion, the present study indicates that the genetic risk for IBD is not modulated by MTHFR C677T polymorphism in Moroccan population.