Frequency of Hereditary Hemochromatosis (HFE) Gene Mutations in Egyptian Beta Thalassemia Patients and its Relation to Iron Overload

AIM: This study aimed to detect the most common HFE gene mutations (C282Y, H63D, and S56C) in Egyptian beta thalassemia major patients and its relation to their iron status. SUBJECTS AND METHODS: The study included 50 beta thalassemia major patients and 30 age and sex matched healthy persons as a control group. Serum ferritin, serum iron and TIBC level were measured. Detection of the three HFE gene mutations (C282Y, H63D and S65C) was done by PCR-RFLP analysis. Confirmation of positive cases for the mutations was done by sequencing.RESULTS: Neither homozygote nor carrier status for the C282Y or S65C alleles was found. The H63D heterozygous state was detected in 5/50 (10%) thalassemic patients and in 1/30 (3.3%) controls with no statistically significant difference between patients and control groups (p = 0.22). Significantly higher levels of the serum ferritin and serum iron in patients with this mutation (p = 001).CONCLUSION: Our results suggest that there is an association between H63D mutation and the severity of iron overload in thalassemic patients

Correlation of circulating miRNA-33a and miRNA-122 with lipid metabolism among Egyptian patients with metabolic syndrome

Abstract Background Metabolic syndrome is defined as a group of interrelated biochemical, clinical, and metabolic factors that directly increase the risk of cardiovascular disease, obesity, and type 2 diabetes mellitus. MicroRNA-33a (miR-33a) and MicroRNA-122 (miR-122) play a crucial role in various biological processes by regulating the gene expression level through post-transcriptional mechanisms, and alterations of their levels are associated with lipid and glucose metabolic disorders. In the present study, we aimed to investigate the correlation of miR-33a and miR-122 with obesity indices and glycemic parameters in a cohort of Egyptian patients. Quantitative real-time polymerase chain reaction (RT-PCR) using TaqMan assay was carried out to estimate the expression levels of miR-33a and miR-122 in serum samples of 100 patients diagnosed as having metabolic syndrome and 50 healthy controls. All patients (100%) had type 2 diabetes (by both history and laboratory assessment) and 70% were obese (BMI ≥ 30 kg/m2). Results Compared to controls, patients had significantly higher serum expression level of miR-33a (p value < 0.001) and miR-122 (p value = 0.0016). miR-33a was less expressed (downregulation expression) with 0.8 fold change in the patient group (obese and diabetic) compared to healthy controls, while miR-122 was highly expressed (upregulation expression) in the patient group of patients with 1.9 fold change. Clinical parameters as body mass index (BMI), wrist circumference (Wc), weight (Wt), and height (Ht) (all p < 0.001); total cholesterol (TC) (p = 0.0115); and triglyceride (TG) (p = 0.0286), all were significantly higher in patients compared to the healthy group. Both miRNAs show statistically significant correlations with clinical and biochemical parameters (p < 0.001). Conclusions Circulating miR-33a and miR-122 might be convincing as possible biomarkers for the diagnosis of metabolic syndrome

Gene mutations of the three ectodysplasin pathway key players (EDA, EDAR, and EDARADD) account for more than 60% of Egyptian ectodermal dysplasia: A report of seven novel mutations

Ectodermal dysplasia (ED) is a diverse group of genetic disorders caused by congenital defects of two or more ectodermal-derived body structures, namely, hair, teeth, nails, and some glands, e.g., sweat glands. Molecular pathogenesis of ED involves mutations of genes encoding key proteins of major developmental pathways, including ectodysplasin (EDA) and wingless-type (WNT) pathways. The most common ED phenotype is hypohidrotic/anhidrotic ectodermal dysplasia (HED) featuring hypotrichosis, hypohidrosis/anhidrosis, and hypodontia. Molecular diagnosis is fundamental for disease management and emerging treatments. We used targeted next generation sequencing to study EDA, EDAR, EDARADD, and WNT10A genes in 45 Egyptian ED patients with or without hypohidrosis. We present genotype and phenotype data of 28 molecularly-characterized patients demonstrating genetic heterogeneity, variable expressivity, and intrafamilial phenotypic variability. Thirteen mutations were reported, including four novel EDA mutations, two novel EDARADD, and one novel EDAR mutations. Identified mutations congregated in exons encoding key functional domains. EDA is the most common gene contributing to 85% of the identified Egyptian ED genetic spectrum, followed by EDARADD (10%) and EDAR (5%). Our cohort represents the first and largest cohort from North Africa where more than 60% of ED patients were identified emphasizing the need for exome sequencing to explore unidentified cases