INF2 and ROBO2 gene mutation in an Indian family with end stage renal failure and follow-up of renal transplantation.

BACKGROUND: Accurate genetic diagnosis of end-stage renal disease patients with a family history of renal dysfunction is very essential. It not only helps in proper prognosis, but becomes crucial in designating donor for live related renal transplant. We here present a case of family with deleterious mutations in INF2 and ROBO2 and its importance of genetic testing before preparing for kidney transplantation. CASE PRESENTATION: We report the case of a 29-year-female with end-stage renal disease and rapidly progressive renal failure. Mutational analysis revealed an Autosomal Dominant inheritance pattern and mutation in exon 4 of the INF2 gene (p. Thr215Ser) and exon 26 of the ROBO2 gene (p. Arg1371Cys). Her mother was diagnosed for CKD stage 4 with creatinine level of 4.3 mg/dL. Genetic variants (INF2 and ROBO2) identified in proband were tested in her sisters and mother. Her elder sister was positive for both heterozygous variants (INF2 and ROBO2). Her mother was positive for mutation in INF2 gene, and her donor elder sister did not showed mutation in INF2 gene and had mutation in ROBO2 gene without any clinical symptoms. CONCLUSION: This case report emphasize that familial genetic screening has allowed us in allocating the donor selection in family where family member had history of genetic defect of Chronic Kidney Disease. Information of the causative renal disorder is extremely valuable for risk-assessment and planning of kidney transplantation.

Restoring Ravaged Heart: Molecular Mechanisms and Clinical Application of miRNA in Heart Regeneration.

Human heart development is a complex and tightly regulated process, conserving proliferation, and multipotency of embryonic cardiovascular progenitors. At terminal stage, progenitor cell type gets suppressed for terminal differentiation and maturation. In the human heart, most cardiomyocytes are terminally differentiated and so have limited proliferation capacity. MicroRNAs (miRNAs) are non-coding single-stranded RNA that regulate gene expression and mRNA silencing at the post-transcriptional level. These miRNAs play a crucial role in numerous biological events, including cardiac development, and cardiomyocyte proliferation. Several cardiac cells specific miRNAs have been discovered. Inhibition or overexpression of these miRNAs could induce cardiac regeneration, cardiac stem cell proliferation and cardiomyocyte proliferation. Clinical application of miRNAs extends to heart failure, wherein the cell cycle arrest of terminally differentiated cardiac cells inhibits the heart regeneration. The regenerative capacity of the myocardium can be enhanced by cardiomyocyte specific miRNAs controlling the cell cycle. In this review, we focus on cardiac-specific miRNAs involved in cardiac regeneration and cardiomyocyte proliferation, and their potential as a new clinical therapy for heart regeneration.

Emerging role of Piezo ion channels in cardiovascular development.

Mechanical cues are crucial for vascular development and the proper differentiation of various cell types. Piezo1 and Piezo2 are mechanically activated cationic channels expressed in various cell types, especially in vascular smooth muscle and endothelial cells. It is present as a transmembrane homotrimeric complex, regulating calcium influx. Local blood flow associated shear stress, in addition to blood pressure associated cell membrane stretching are key Piezo channel activators. There is rising proof, showcasing Piezo channels significance in myocytes, cardiac fibroblast, vascular tone maintenance, atherosclerosis, hypertension, NO generation, and baroreceptor reflex. Here, we review the role of Piezo channels in cardiovascular development and its associated clinical disorders. Also, emphasizing on Piezo channel modulators which might lead to novel therapies for cardiovascular diseases.

Recent trends in targeting miRNAs for cancer therapy.

OBJECTIVES: MicroRNAs (miRNAs) are a type of small noncoding RNA employed by the cells for gene regulation. A single miRNA, typically 22 nucleotides in length, can regulate the expression of numerous genes. Over the past decade, the study of miRNA biology in the context of cancer has led to the development of new diagnostic and therapeutic opportunities. KEY FINDINGS: MicroRNA dysregulation is commonly associated with cancer, in part because miRNAs are actively involved in the mechanisms like genomic instabilities, aberrant transcriptional control, altered epigenetic regulation and biogenesis machinery defects. MicroRNAs can regulate oncogenes or tumour suppressor genes and thus when altered can lead to tumorigenesis. Expression profiling of miRNAs has boosted the possibilities of application of miRNAs as potential cancer biomarkers and therapeutic targets, although the feasibility of these approaches will require further validation. SUMMARY: In this review, we will focus on how miRNAs regulate tumour development and the potential applications of targeting miRNAs for cancer therapy.