miRNA Genetic Variants Alter Their Secondary Structure and Expression in Patients With RASopathies Syndromes.

摘要: RASopathies are a group of rare genetic diseases caused by germline mutations in genes involved the RAS-mitogen-activated protein kinase (RAS-MAPK) pathway. Whole-exome sequencing (WES) is powerful approach for identifying new variants coding and noncoding DNA sequences, including miRNAs. miRNAs fine-tuning negative regulators gene expression. The presence could lead to malfunctions regulation, resulting diseases. Here, we identified 41 mature through WES analysis five patients with previous clinical diagnosis syndromes. pathways, biological processes, that were over-represented among target harboring included RAS, MAPK, RAP1, PIK3-Akt signaling neuronal differentiation, neurogenesis nervous system development, congenital cardiac defects (hypertrophic cardiomyopathy, dilated arrhythmogenic right ventricular cardiomyopathy), phenotypes syndromes (Noonan syndrome, Legius Costello Cafe au lait spots multiple, subaortic stenosis, pulmonary valve LEOPARD syndrome). Furthermore, eight selected nine (hsa-miR-1304, hsa-miR-146a, hsa-miR-196a2, hsa-miR-499a/hsa-miR-499b, hsa-miR-449b, hsa-miR-548l, hsa-miR-575, hsa-miR-593) may have alterations secondary structures miRNA precursor. Selected containing such as hsa-miR-146a-3p, hsa-miR-196a-3p, hsa-miR-449b-5p, hsa-miR499a-3p regulate classical associated Rasopathies RAS-MAPK contributing modify expression pattern patients. RT-qPCR revealed four differentially expressed downregulated: miRNA-146a-3p P1, P2, P3, P4, P5, miR-1304-3p miR-196a2-3p miR-499b-5p P1. miR-499a-3p was upregulated P5. These results indicate show different patterns when these present Therefore, this study characterized role related first time indicated possible implications cardio-cerebrovascular existence be used biomarkers RASopathies.