A seed sequence variant in miR-145-5p causes multisystem smooth muscle dysfunction syndrome

• Published in: The Journal of clinical investigation Vol. 133; no. 5; pp. 1 - 3
• Main Authors: Lino Cardenas, Christian Lacks, Briere, Lauren C, Sweetser, David A, Lindsay, Mark E, Musolino, Patricia L
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.03.2023
• Subjects: Actin; Aortic aneurysms; Biomedical research; Blood circulation disorders; Cell Proliferation; Cells, Cultured; Cerebrovascular disease; Complications and side effects; Cytoskeleton; Diagnosis; Fibroblasts; Gene mutations; Genetic aspects; Genetic disorders; Genetic diversity; Genotype & phenotype; Health aspects; Identification and classification; MicroRNA; MicroRNAs - genetics; Muscle, Smooth; Mutation; Myocytes, Smooth Muscle - physiology; Phenotypes; Physiological aspects; Research Letter; siRNA; Smooth muscle; Transfection; Vascular biology; United States; Cardiovascular disease; Stroke; Vascular Biology
• ISSN: 1558-8238; 0021-9738; 1558-8238
• DOI: 10.1172/JCI166497

Transfection of either siRNA against miR-145-5p or the mutant miR-145-5p induced a phenotype characterized by deficient F-actin, whereas treatment with WT miR-145-5p enhanced stress fiber formation (Figure 1E). [...]we next performed RNA-seq analysis that included mRNAs and miRs in patient skin fibroblasts and compared them to WT skin fibroblasts. Furthermore, pathway analysis of DEGs showed enrichment of categories related to "hsa04810: regulation of actin cytoskeleton" (Supplemental Figure 3). [...]genetic variation in the MIR145 gene expands the possible loci associated with MSMDS and further confirms the syndrome as a disorder of failed SMC development and function, although discovery of further cases will be necessary to confirm our findings.