Next-Generation Sequencing Reveals One Novel Missense Mutation in COL1A2 Gene in an Iranian Family with Osteogenesis imperfect

Background: Osteogenesis imperfecta [Ol] is a clinically and genetically heterogeneous disorder characterized by bone loss and bone fragility. The aim of this study was to investigate the variants of three genes involved in the pathogenesis of Ol

Methods: Molecular genetic analyses were performed for COLlAl, COL1A2, and CRTAP genes in an Iranian family with Ol. The DNA samples were analyzed by next-generation sequencing [NGS] gene panel and Sanger sequencing

Results: Five different variants were identified in COLlAl and COL1A2, including two variants in COLlAl and three variants in COL1A2. Among the five causative COLlAl and COL1A2 variants, one novel variants, c.1081 G>A, was found in COL1A2, which was identified in two siblings

Conclusion: Our finding extends the variant spectrum of the COL1A2 gene and has important implications for genetic counseling of families. The NGS is a powerful molecular diagnostic strategy for Ol, a heterogeneous disorder

MicroRNA expression in beta-Thalassemia and sickle cell disease: a role in the induction of fetal hemoglobin

Today the regulatory role of microRNAs [miRs] is well characterized in many diverse cellular processes. MiR-based regulation is categorized under epigenetic regulatory mechanisms. These small non-coding RNAs participate in producing and maturing erythrocytes, expressing hematopoietic factors and regulating expression of globin genes by post-transcriptional gene silencing. The changes in expression of miRs [miR-144/-320/-451/-503] in thalassemic/sickle cells compared with normal erythrocytes may cause clinical severity. According to the suppressive effects of certain miRs [miR-15a/-16-1/-23a/-26b/-27a/-451] on a number of transcription factors [myeloblastosis oncogene [MYB], B-cell lymphoma 11A [BCL11A], GATA1, Krüppel-like factor 3 [KLF3] and specificity protein 1 [Sp1]] during beta globin gene expression, It has been possible to increasing ? globin gene expression and fetal hemoglobin [HbF] production. Therefore, this strategy can be used as a novel therapy in infusing HbF and improving clinical complications of patients with hemoglobinopathies

Molecular aspects of bone resorption in beta-thalassemia major

Beta-thalassemia is the most common single gene disorder worldwide, in which hemoglobin beta-chain production is decreased. Today, the life expectancy of thalassemic patients is increased because of a variety of treatment methods; however treatment related complications have also increased. The most common side effect is osteoporosis, which usually occurs in early adulthood as a consequence of increased bone resorption. Increased bone resorption mainly results from factors such as delayed puberty, diabetes mellitus, hypothyroidism, ineffective hematopoiesis as well as hyperplasia of the bone marrow, parathyroid gland dysfunction, toxic effect of iron on osteoblasts, growth hormone [GH] and insulin-like growth factor-1 [IGF-1] deficiency. These factors disrupt the balance between osteoblasts and osteoclasts by interfering with various molecular mechanisms and result in decreased bone density. Given the high prevalence of osteopenia and osteoporosis in thalassemic patients and complexity of their development process, the goal of this review is to evaluate the molecular aspects involved in osteopenia and osteoporosis in thalassemic patients, which may be useful for therapeutic purposes

[Pattern of dystrophin gene deletions in patients affected by Duchenne muscular dystrophy in Ahwaz City]

About 40-70% of all mutations in dystrophin gene in Duchenne muscular dystrophy [DMD] are deletions, but large variations in the proportion of intragenic deletions in the dystrophin gene have been observed in different populations. In order to further investigate the geographical and ethnic variations, the present study reports our findings on the proportion and pattern of deletional mutations in DMD patients from Ahwaz City. In the present study, DNA samples from 10 unrelated DMD patients were analyzed for deletional mutations using multiplex PCR. A total of 6 patients [60%] showed intragenic deletions in the dystrophin gene; 3 in the proximal hot spot and 3 in the central hot spot. The observed proportion of gene deletions is relatively high, particularly compared with those of European and Asian countries and similar to that of North India. However, the distribution of breakpoints across the gene does not show significant variation