Investigation of JAK2V617F Mutation Prevalence in Patients with Beta Thalassemia Major.

BACKGROUND: Beta (ß)-thalassemia major is a genetic disorder with anemia and an increased level of erythropoietin by Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway. JAK plays an important role in cell signaling, and the common mutation in the JAK2 gene in myeloid disorders is called JAK2V617F. METHODS: A total of 75 patients with beta (ß)-thalassemia major patients, including 34 males (45%) and 41 females (55%), were enrolled in this study. The presence of the JAK2V617F mutation was assessed using the amplification-refractory mutation-polymerase chain reaction (ARMS-PCR) technique. RESULTS: Among the 75 patients, 14 patients (19%) tested positive and 61 patients (81%) tested negative for JAK2V617F mutation. We observed no statistically significant difference in sex, age, genotype, and JAK2V617F mutation among patients (P> .05). However, a significant difference between blood-transfusion frequency and JAK2V617F mutation was observed (P <.05). CONCLUSION: Due to the low prevalence of JAK2V617F mutation in thalassemia, using a larger population of the patients to investigate this mutation in ineffective erythropoiesis can be useful.

Molecular determination of glutaric aciduria type I in individuals from southwest Iran.

BACKGROUND: Glutaric Aciduria type 1 (GA1) is a metabolic inborn error and is characterized by increasing excursion of glutaric acid and its derivates, presented in microcephaly and dystonia. The disease is resulted from mutational inactivation in the GCDH gene encoding the glutaryl-CoA dehydrogenase. The defective enzyme causes the accumulation of an excessive level of intermediate breakdown products that leads to the brain damage. In spite of the clinical features, diagnosis of GAI has been often confusing, because of variability in the clinical manifestations of patients. Early diagnosis and treatment can though prevent irreversible disease progression and consequent brain damage; otherwise the affected individuals will die in their first decade of lives. METHODS: The GCDH gene was also analyzed to (detect or identify) disease causing mutations using gene amplification and direct sequencing in 18 patients. RESULTS: Among 18 patients, 10 patients (55.5%) were homozygous or compounded heterozygous for the recurrent mutation E181Q, three patients (16.7%) were homozygous for the known mutation R402Q and one patient (5.6%) was compound heterozygous for S255L. All three detected missense mutations are pathogenic, which cause structural changes in the binding site and tetramerization or functional deficiency. Four other individuals (22.2%) with a preliminary diagnosis of GAI were negative for any pathogenic mutations. CONCLUSION: Most GA1 affected persons in southwest Iran are with Persian ethnicity and the most common mutation in Khuzestan Province is prominent in comparison to  previous reports from Iran.

Breast cancer frequency and exposure to cadmium: a meta- analysis and systematic review.

BACKGROUND: In this meta-analysis we review evidence suggesting that exposure to cadmium is a cause of breast cancer. MATERIALS AND METHODS: We conducted Medline/PubMed and Scopus searches using selected MeSH keywords to identify papers published from January 1, 1980 through January 1, 2013. Data were merged and summary mean differences were estimated using either a random-effects model or a fixed-effects model. RESULTS: There were 13 studies including 978 exposed cases and 1,279 controls. There was no statistically significant difference in the frequencies of breast cancer between cadmium-exposed and control groups, and the summary estimate of mean difference was 0.71 (95%CI: 0.33-1.08). However, stratification showed that there were statistically significant differences in the frequencies of breast cancer between cadmium-exposed and control groups among Asian compared with Caucasian population, and the summary estimates of mean difference were 1.45 (95%CI: 0.62-2.28) vs. 0.25 (95%CI: -0.09-0.6), respectively. There was a difference in the frequencies of breast cancer between cadmium-exposed and control groups in peripheral venous blood sampling methods, and the summary estimate of mean difference was 1.41 (95%CI: 0.46-2.37). CONCLUSIONS: Data indicate that the frequencies of breast cancer might be an indicator of early genetic effects for cadmium-exposed populations. However, our meta-analysis was performed on population-based studies; meta-analysis based on individual data might provide more precise and reliable results. Therefore, it is necessary to construct an international database on genetic damage among populations exposed to cadmium that may contain all raw data of studies examining genetic toxicity.

New Single Nucleotide Deletion In the SMPD1 Gene Causes Niemann Pick Disease Type A in a Child from Southwest Iran: A Case Report.

OBJECTIVE: NIEMANN PICK DISEASE (NPD) TYPE A (NPA: MIM #257200) is a lipid storage disorder with an autosomal recessive inheritance and occurrs by defect of the SMPD1 gene encoding sphingomyelinase. Disruption of this enzyme leads to the accumulation of sphingomyelin in brain and liver, which in turn causes dysfunction or damage of tissue. METHODS: We report firstly a 2.5 year old boy with NPA in southwest Iran. Initially, the diagnosis was resulted on the basis of clinical symptoms. The genomic DNA of the suspected individual was subjected to exon sequencing of the SMPD1 gene. According to the human reference sequence NM_000543.4, a novel single guanine deletion resulting in a frameshift mutation (p.Gly247Alafs*9) was observed in the SMPD1 gene that might be causative for the outcome of the disease. FINDINGS: The present report is the first molecular genetics diagnosis of the NPA in southwest Iran. The detected deletion in the SMPD1 gene is remarkable because of its novelty. CONCLUSION: Despite similar morbidity SGA infants exhibited higher lethal complication rates following delayed meconium passage compared to AGA infants.