Jummanah Jarullah

Molecular characterization of glucose-6-phosphate dehydrogenase deficiency in Jeddah, Kingdom of Saudi Arabia

BackgroundThe development of polymerase chain reaction (PCR)-based methods for the detection of known mutations has facilitated detecting specific red blood cell (RBC) enzyme deficiencies. We carried out a study on glucose-6-phosphate dehydrogenase (G6PD) deficient subjects in Jeddah to evaluate the molecular characteristics of this enzyme deficiency and the frequency of nucleotide1311 and IVS-XI-93 polymorphisms in the glucose-6-phosphate dehydrogenase gene.ResultsA total of 1584 unrelated Saudis (984 neonates and 600 adults) were screened for glucose-6-phosphate dehydrogenase deficiency. The prevalence of glucose-6-phosphate dehydrogenase deficiency was 6.9% (n = 110). G6PD Mediterranean mutation was observed in 98 (89.1%) cases, G6PD Aures in 11 (10.0%) cases, and G6PD Chatham in 1 (0.9%) case. None of the samples showed G6PD A‾ mutation. Samples from 29 deficient subjects (25 males and 4 females) were examined for polymorphism. The association of two polymorphisms of exon/intron 11 (c.1311T/IVS-XI-93C) was observed in 14 (42.4%) of 33 chromosomes studied. This association was found in 9 (31.0%) carriers of G6PD Mediterranean and in 4 (13.8%) carriers of G6PD Aures.ConclusionsThe majority of mutations were G6PD Mediterranean, followed by G6PD Aures and < 1% G6PD Chatham. We conclude that 1311T is a frequent polymorphism in subjects with G6PD Mediterranean and Aures variants in Jeddah.

Clinical biomarkers in sickle cell disease.

Sickle cell disease (SCD) is a hereditary blood disorder caused by a single gene. Various blood and urine biomarkers have been identified in SCD which are associated with laboratory and medical history. Biomarkers have been proven helpful in identifying different interconnected disease-causing mechanisms of SCD, including hypercoagulability, hemolysis, inflammation, oxidative stress, vasculopathy, reperfusion injury and reduced vasodilatory responses in endothelium, to name just a few. However, there exists a need to establish a panel of validated blood and urine biomarkers in SCD. This paper reviews the current contribution of biochemical markers associated with clinical manifestation and identification of sub-phenotypes in SCD.

Current Management Strategies in Breast Cancer by Targeting Key Altered Molecular Players.

Breast cancer is the second largest disease affecting women worldwide. It remains the most frequently reported and leading cause of death among women in both developed and developing countries. Tamoxifen and raloxifene are commonly used selective estrogen receptor modulators for treatment of breast cancer in women with high risk, although resistance occurs by tamoxifen after 5 years of therapy and both drugs cause uterine cancer and thromboembolic events. Aromatase inhibitors (AIs) are one of the optional modes used for breast cancer treatment. The combination of AIs along with tamoxifen can also be beneficial. Various therapeutic agents from different sources are being studied, which further need to be improved for potential outcome. For this, clinical trials based on large number of patients with optimal dose and lesser side effects have to be more in practice. Despite the clinical trials going on, there is need of better molecular models, which can identify high risk population, new agents with better benefit having less side effects, and improved biomarkers for treating breast cancer.

Detection of Glucose-6-Phosphate Dehydrogenase Deficiency in Heterozygous Saudi Female Neonates

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy affecting 400 million people, globally. G6PD deficiency is an X-linked genetic condition, which is more likely to affect males than females. Heterozygous females go undetected in commonly used method. The aim of the study was to identify & validate female heterozygous neonates, missed in neonatal screening programs. Methods: Blood samples were collected from 984 Saudi neonates (448 Male and 536 Female) in EDTA tubes for quantitative evaluation of G6PD enzyme activity. Quantitative evaluation was done by Sigma diagnostic kits (No. 345-UV). The reduction of nicotinamide adenine dinucleotide phosphate to nicotinamide adenine dinucleotide phosphate oxidase, reflecting G6PD activity was measured spectrophotometrically. Hemoglobin (Hb) was measured on the same sample. G6PD activity was recorded as U/g Hb. Samples identified as deficient with cutoff ≤6.6 U/gHb were subjected to molecular genotyping for common G6PD variants. Results: Out of 448 male neonates, 47 (10.3%) were designated as G6PD deficient with average G6PD enzyme activity of 1.89 U/gHb. Females (536) showed continuum results. With ≤ 4.6 U/gHb cutoff, 14 (2.6%) female neonates were designated as G6PD deficient with average G6PD enzyme activity of 2.6 U/gHb, while with cutoff ≤ 6.6 U/gHb, 34 (6.3%) with average G6PD enzyme activity of 5.5 U/gHb were marked deficit. Additional neonates which were designated as deficit with cutoff ≤ 6.6 U/gHb showed presence of G6PD mutations, 18 (80%) showed G6PD Mediterranean, and 2 (20%) were identified a G6PD Aures. Conclusion: Considerable amounts of partially deficient G6PD female heterozygous are missed, when ≤ 4.6 U/gHb cutoff is used to identify deficient female neonates, however, deficient males, hemizygotes were detected efficiently with ≤ 4.6 U/gHb as cutoff point. Higher reference value (≤ 6.6 U/gHb) is recommended for female neonates.

Effect of iron overload on renal functions and oxidative stress in beta thalassemia patients

Objectives: To check the amount of cellular damage caused by serial transfusions of blood in thalassemia patients. Methods: A cross-sectional study was conducted in the University of Lahore, Lahore, Pakistan between August 2012 and December 2012. A total of 43 thalassemia patients underwent at least 10 blood transfusions. Comprehensive biochemical analysis of blood was performed to record the levels of creatinine, urea, uric acid, albumin, liver function tests, malondialdehyde (MDA), and ferritin. Results: Serum creatinine (0.732±0.23mg/dl) and uric acid (6.7±0.94mg/dl, p<0.05) were significantly higher in patient groups as compared with the control. Ferritin levels were significantly higher in patients as compared with the control (3103.9±1747.4, p<0.05). Hemoglobin levels were observed in controls 14±1.3g/dl and in patients 7.1±1.03g/dl. No clear relationship exists between age and hematological parameters of thalassemic patients. Serum ferritin level is positively related with serum alanine transaminase, aspartate aminotransferase, and alkaline phosphatase and MDA (p<0.05). Conclusion: Serum MDA and serum ferritin of patients (r=0.593, p<0.05) reflects that both are crucial parameters estimating the cellular damage in patients suffering from thalassemia.

Comparative In-Silico Study of β-Tubulin Proteins from Arthrobotrys musiformis for Resistance to Benzimidazole

Arthrobotrys musiformis is a biocontrol agents which can be used in the integrated pest management strategies. Although this isolate was found to show high benzimidazole resistance as compared to the other biocontrol agents, considering the dose of administration of anthelmintics, a need for developing an improved strain of this fungus resistant to chemical anthelimintics was observed. In the present study improved strains of Arthrobotrys musiformis were obtained using random mutagenesis technique carried out both by chemical mutagenic agent, Ethyl methane sulfonate (EMS) and physical mutagenic agent, UV radiation. The obtained mutants were screened using their ability to survive in high benzimidazole concentration, isolated, selected based on their biocontrol activity and characterized for their suitability as biocontrol agents. The β-tubulin genes of the selected mutants were finally studied.

Clinical Genotypic Correlation of Beta S-Globin Haplotypes in Sickle Cell Anemia

Sickle cell disease played a pioneering role in the establishment of the field of molecular medicine. Even though this disease was identified many years ago its clinical course is still not clear. Clinical severity ranges across individuals, even within the same ethnic group. Molecular studies have identified different haplotypes across the globin gene cluster. Correlating individual haplotypes with clinical severity has become the primary focus in the endeavour to establish a successful treatment. Even though numerous studies have been performed, most have shown a negative correlation between beta S-globin haplotypes and clinical phenotype. After a review of recent medical literature, the authors conclude that further research translating genetic analysis to positive therapeutic response for sickle cell disease patients is needed.