Deletions Overlapping VCAN Exon 8 Are New Molecular Defects for Wagner Disease
HUMAN MUTATION
Authors: Burin-des-Roziers, Cyril; Rothschild, Pierre-Raphael; Layet, Valerie; Chen, Jian-Min; Ghiotti, Tiffany; Leroux, Celine; Cremers, Frans P. M.; Brezin, Antoine P.; Valleix, Sophie
Abstract
Wagner disease is a rare nonsyndromic autosomal-dominant vitreoretinopathy, associated with splice mutations specifically targeting VCAN exon 8. We report the extensive genetic analysis of two Wagner probands, previously found negative for disease-associated splice mutations. Next-generation sequencing (NGS), quantitative real-time PCR, and long-range PCR identified two deletions (3.4 and 10.5 kb) removing at least one exon-intron boundary of exon 8, and both correlating with an imbalance of VCAN mRNA isoforms. We showed that the 10.5-kb deletion occurred de novo, causing somatic mosaicism in the proband's mother who had an unusually mild asymmetrical phenotype. Therefore, exon 8 deletions are novel VCAN genetic defects responsible for Wagner disease, and VCAN mosaic mutations may be involved in the pathogenesis of Wagner disease with attenuated phenotype. NGS is then an effective screening tool for genetic diagnosis of Wagner disease, improving the chance of identifying all disease-causative variants as well as mosaic mutations in VCAN.
miRNA-mediated Expression Switch of Cell Adhesion Genes Driven by Microcirculation in Chip
BIOCHIP JOURNAL
Authors: Samatov, Timur R.; Galatenko, Vladimir V.; Senyavina, Nadezhda V.; Galatenko, Alexey V.; Shkurnikov, Maxim Yu; Tonevitskaya, Svetlana A.; Sakharov, Dmitry A.; Marx, Uwe; Ehrlich, Hermann; Schumacher, Udo; Tonevitsky, Alexander G.
Abstract
Changes in cell adhesion molecule (CAM) expression and miRNAs regulating them are known to be involved in malignant progression in colon cancer. We investigated expression profiles of CAM genes and non-coding RNAs in CaCo2 colon cancer cells in static culture and under dynamic flow conditions perfused in microfluidic chip emulating physiological microenvironment. We incubated monolayers of CaCo2 cells in TranswellA (R) units either under static conditions or under flow in a microfluidic chip. We identified 7 up-regulated CAM genes (CD44, CDH7, CEACAM5, CEACAM6, CYR61, L1CAM and VCAN), 7 down-regulated genes (COL12A1, FGA, FGB, FGG, GJA1, ITGA5 and LAMA1) and 69 miRNAs targeting them under the influence of microcirculation. The revealed network comprised CAM genes known to interact with each other and 13 miRNAs simultaneously regulating more than one of them. The discovered regulatory network comprising CAM genes and miRNAs is likely involved in normal functioning of intestine epithelium as well as in cancer progression.
COA
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