Computational Analysis of BRCA1 Mutations in Pediatric Patients with Malignancies and Their Mothers BRCA1 and BRCA2 Mutations in Childhood ALL

Breast and ovarian cancers are the most prevalent type of malignancies amongst women. Similar incidence appear in childhood malignancies, where the basic ontogenetic mechanisms still remain to be elucidated. Such approaches, of relating mother's cancer mutations with the prevalence of childhood cancer in their offspring could prove useful in the prognosis, early detection and therapy of childhood malignancies. The aim of the present study was to use computational and bioinformatics tools to investigate the incidence of mutations in mothers with children suffering from neoplasms. Genes were examined for mutations and in particular, those were BRCA1, RAS family genes, TP53 and FLT3. Mutations were initially detected using PCR and multiplex Polymerase Chain Reaction (PCR) methodologies. Gene expression was detected using quantitative Reverse Transcription PCR (qRT-PCR) methodologies and results have been confirmed with the sequencing method. Following experimental analysis, bioinformatics analyses have been performed. In the case of positive identification of mutations, molecular modelling was used in order to study the effects of the mutations on the BRCA protein and subsequent effects on binding to BARD1, a signaling molecule down-stream of BRCA1, which participates in DNA repair pathways. Concluding, it appeared that the presence of a mutation in the aforementioned genes is not adequate for the disease to progress, yet it can be considered as a serious factor for disease progression. Thus, it appears that this phenomenon is of extreme interest and it should be further investigated in a larger patient cohort

National registry of hemoglobinopathies in Greece: updated demographics, current trends in affected births, and causes of mortality

National registries constitute an invaluable source of information and contribute to the improvement of hemoglobinopathy management. Herein, we present the second updated report of the National Registry for Haemoglobinopathies in Greece (NRHG) and critically discuss the time trends in demographics, affected births, and causes of mortality. Thirty-eight Greek hemoglobinopathy units reported data from diagnosis to the last follow-up or death by retrospectively completing an electronic form. Four thousand thirty-two patients were eligible for inclusion; more than half of them had thalassaemia major. Compared to the previous report, a reduction in the total number of all hemoglobinopathies except for hemoglobinopathy was evident. The total number of affected births was also reduced; most of them were attributable to diagnostic errors and lack of awareness. Importantly, data on iron overload are reported for the first time; although most patients had low or moderate liver iron concentration (LIC) values, a non-negligible proportion of patients had high LIC. The burden due to heart iron overload was less prominent. Cardiac- and liver-related complications are the major causes of morbidity and mortality. From 2000 to 2015, a decrease in heart-related deaths along with an increase in liver-associated fatalities was observed. The Hellenic Prevention Program along with advances in chelation regimens and iron status monitoring have resulted in improved patient outcomes. The NRHG gives insight into the effectiveness of prevention programs, the therapeutic management of hemoglobinopathies and associated outcomes. NRHG may contribute to the formulation of a roadmap for hemoglobinopathies in Europe and promote the implementation of effective public health policies