Thalassemia — From Genotype to Phenotype

Thalassemia encompasses serious diseases with complex pathophysiology that is difficult to explain since it is considered a group of defects with similar clinical effects, still not a single disorder

Assessment of the −174G/C (rs1800795) and −572G/C (rs1800796) Interleukin 6 Gene Polymorphisms in Egyptian Patients with Rheumatoid Arthritis

AIM: This study aimed to investigate genotype and allele frequencies of −174 (rs1800795) and −572 (rs1800796) IL-6 promoter gene polymorphisms in Egyptian patients with rheumatoid arthritis (RA) in comparison to control group.METHODS: The study was conducted on 198 Egyptian subjects (99 RA patients and 99 healthy control).The promoter region of the IL-6 gene was amplified by PCR using DNAs from patients and the controls, and their PCR products were digested by suitable enzymes.RESULTS: No statistical differences were found in −572G/C genotype (P = 0.177) or allele (P = 0.147) frequencies between RA patients and controls. Significant differences were observed in −174G/C genotype (P ˂ 0.001) and allele (P ˂ 0.001) frequencies between RA patients and controls.CONCLUSION: A significant association of IL-6 −174G/C gene polymorphism and RA in Egyptian population was found with significantly higher frequencies of GC and CC genotypes and C allele in RA patients compared to controls. No association was found between IL-6 −572G/C gene polymorphism and RA

Is there a Link between Human Herpes Virus Infection and Toll-like Receptors in the Pathogenesis of Pityriasis Rosea? A Case-control Study

Human herpesvirus (HHV) 6 and 7 are involved in the pathogenesis of pityriasis rosea (PR). Our aim was to evaluate the role of the innate immune response in PR through the detection of Toll-like receptors (TLR) 2, 3, 4, 7, 8, and 9 expression in the skin of affected patients and to detect the possibility of being induced by HHV-6 and/or HHV-7 viral coexistence in these patients. Twenty-four patients with PR and 24 healthy controls were included in this case-control study. Biopsy was obtained from the PR lesion and from the healthy skin of controls for detection of HHV-6 and 7 as well as TLRs 2, 3, 4, 7, 8, and 9 gene expression using real-time polymerase chain reaction (PCR). Significantly elevated expression of all studied TLRs and significantly higher viral load of HHV-6 and 7 in PR cases were detected. A significant higher expression of TLR2 and 4 in HHV-7 positive cases and a significant positive correlation between TLR9 and HHV-7 viral load were documented. HHV6 and 7 may also be involved in the pathogenesis of PR via TLR pathways  </p

Association of the Pro12Ala Polymorphism with the Metabolic Parameters in Women with Polycystic Ovary Syndrome

AIM: To investigate the association of peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala polymorphism with polycystic ovary syndrome (PCOS) and its effect on the metabolic parameters in PCOS women.METHODS: The study used PCR to identify the presence of the PPARG Pro12Ala polymorphism in 100 PCOS women and 120 age-matched healthy women. All participants were subjected to anthropometry, biochemical and metabolic evaluation.RESULTS: Significant difference in the genotypes distributions of PPARG Pro12Ala polymorphism was observed among PCOS women and controls (p = 0.03). The frequency of the polymorphic allele Ala was significantly higher in PCOS cases than that in the controls (OR = 2.01, p = 0.01). The carries of the variant allele Ala in PCOS women showed significant higher values in body mass index (BMI), systolic and diastolic blood pressure, waist circumference, waist to hip ratio, sum of skin folds, fasting blood glucose, fasting blood insulin, HOMA-IR, fasting triglycerides, total cholesterol and low-density lipoprotein than non-carriers.CONCLUSION: The PPARG Pro12Ala polymorphism might contribute to the risk of PCOS and abnormal metabolic parameters and could be considered as a biomarker for early diagnosis and clinic prediction of metabolic complications

Screening of dystrophin gene deletions in Egyptian patients with DMD/BMD muscular dystrophies

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations within the dystrophin gene. Our study has identified 100 Egyptian families collected from the Human Genetics Clinic, National Research Center, Cairo. All cases were subjected to complete clinical evaluation pedigree analysis, electromyography studies, estimation of serum creatine phosphokinase enzyme (CPK) levels and DNA analysis. Multiplex PCR using 18 pairs of specific primers were used for screening of deletion mutations within the dystrophin gene. A frequency of 55% of deletions were found among the families. Sixty per cent of detected deletions involved multiple exons spanning the major or the minor hot spot of the dystrophin gene. The remainder 40% involved single exon deletions, which mainly involved exon 45. Comparing these findings with frequencies of other countries it was found that our figures fall within the reported range of 40%-60% for deletions. The distribution of deletions in our study and other different studies was variable and specific ethnic differences do not apparently account for specific deletions. In addition this study concluded that employment of the 18 exon analysis is a cost effective and a highly accurate (97% detection rate) method to be considered when planning to launch a nationwide program

Analysis of NPHS2 Gene Mutations in Egyptian Children with Nephrotic Syndrome

BACKGROUND: Mutations in the NPHS2 genes are the main aetiology of early-onset and familial steroid-resistant nephrotic syndrome (SRNS). The pathogenic NPHS2 mutation together with the p.R229Q variant has been less described among Egyptian children. AIM: This study aims to determine the mutation of NPHS2 in children with NS and discover the role of p.R229Q variant in SRNS METHODS: The study included 53 children with NS, and 53 healthy volunteers matched in age and sex controls. The median age at disease onset was 7.3 years. Among NS cases, 31 cases had steroid-sensitive nephrotic syndrome (SSNS) and 22 children with steroid-resistant nephrotic syndrome (SRNS). Polymerase chain reaction amplification of the whole coding region of NPHS2 gene was carried out for its mutational analysis. Restriction digestion testing was carried out after PCR to determine the presence of R229Q polymorphism. Randomly selected samples were re-genotyped by two independent technicians for assessment of Quality control RESULTS: NS patients showed a significant higher frequency of heterozygous genotype GA (89.5%) compared to control group (10.5%) with increased risk of NS (OR, 12.04; 95% CI, 2.61 to55.38; p &lt; 0.0001). Moreover, SRNS showed a significant higher frequency of GA genotype (68.2%) than the SSNS group (6.5%). The GA genotype was associated with increased risk of SRNS (OR, 31.1; 95% CI, 5.73 to 168.48; P &lt; 0.001) and the A allele was associated with increased risk of SRNS (OR, 15.52; 95% CI, 3.325 to 72.422; P &lt; .001). CONCLUSION: R229Q polymorphisms are associated with SRNS, and any child with SRNS should be searched for mutations in the NPHS2 gene

Relation between microRNAs and Apoptosis in Hepatocellular Carcinoma

AIM: To determine the relation between serum microRNAs and apoptotic markers as regards development of HCC to understand the underlying mechanism of HCV related hepatocarcinogenesis. PATIENTS AND METHODS: A total of 65 serum samples (25 samples from controls, 20 samples from hepatitis and 20 samples from HCC patients) were collected for miRNAs (mir 21, mir 199-a, and mir 155) detection. Human Programmed cell death protein-4 (PDCD-4) and Human Cytochrome-C (CYT-C) were determined. RESULTS: miRNAs 21 and 155 were over expressed in sera of patients with HCC compared to patients with chronic hepatitis (p &lt; 0.0001). While serum means values of miR 199a was significantly decreased among HCC group patients when compared to patients with chronic hepatitis (p &lt; 0.0001). The serum levels of PCDC4 and CYTC were increased in patients with HCC when compared to chronic hepatitis patients. They were also increased in patients with chronic hepatitis when compared to controls (p &lt; 0.05, significant). There was direct correlations between apoptotic markers and oncomirs miRNAs 21 and 155 while apoptotic markers were inversely correlated with miRNA 199-a. CONCLUSION: Both microRNAs and apoptotic markers have roles in HCC pathogenesis. It seems that oncogenic microRNAs induce liver carcinogenesis in HCV patients irrespective of suppression of apoptosis.AIM: To determine the relation between serum microRNAs and apoptotic markers as regards development of HCC to understand the underlying mechanism of HCV related hepatocarcinogenesis. PATIENTS AND METHODS: A total of 65 serum samples (25 samples from controls, 20 samples from hepatitis and 20 samples from HCC patients) were collected for miRNAs (mir 21, mir 199-a, and mir 155) detection. Human Programmed cell death protein-4 (PDCD-4) and Human Cytochrome-C (CYT-C) were determined. RESULTS: miRNAs 21 and 155 were over expressed in sera of patients with HCC compared to patients with chronic hepatitis (p &lt; 0.0001). While serum means values of miR 199a was significantly decreased among HCC group patients when compared to patients with chronic hepatitis (p &lt; 0.0001). The serum levels of PCDC4 and CYTC were increased in patients with HCC when compared to chronic hepatitis patients. They were also increased in patients with chronic hepatitis when compared to controls (p &lt; 0.05, significant). There was direct correlations between apoptotic markers and oncomirs miRNAs 21 and 155 while apoptotic markers were inversely correlated with miRNA 199-a. CONCLUSION: Both microRNAs and apoptotic markers have roles in HCC pathogenesis. It seems that oncogenic microRNAs induce liver carcinogenesis in HCV patients irrespective of suppression of apoptosis

Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants.

Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1-/- mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy

APOA2 Polymorphism in Relation to Obesity and Lipid Metabolism

Objectives. This study aims to analysis the relationship between c.-492T>C polymorphism in APOA2 gene and the risk for obesity in a sample of Egyptian adolescents and investigates its effect on body fat distribution and lipid metabolism. Material and Methods. A descriptive, cross-sectional study was conducted on 303 adolescents. They were 196 obese and 107 nonobese, aged 16–19 years old. Variables examined included body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), systolic and diastolic blood pressure (BP), body fat percentage (BF%), abdominal visceral fat layer, and dietary intake. Abdominal visceral fat thickness was determined by ultrasonography. The polymorphism in the APOA2 c.-492T>C was analyzed by PCR amplification. Results. Genotype frequencies were in Hardy-Weinberg equilibrium. The frequency of the mutant C allele was significantly higher in obese cases compared to nonobese. After multivariate adjustment, waist, BF% and visceral adipose layer, food consumption, and HDL-C were significantly higher in homozygous allele CC carriers than TT+TC carriers. Conclusions. Homozygous individuals for the C allele had higher obesity risk than carriers of the T allele and had elevated levels of visceral adipose tissue and serum HDL-C. Moreover, the study shows association between the APOA2 c.-492T>C polymorphism and food consumption