Giovanna Lattanzi
In search of biomarkers for Emery-Dreifuss Muscular Dystrophy
Autori
- ELEONORA CATTIN (DEPT. OF LIFE SCIENCES, UNIVERSITY OF MODENA AND REGGIO EMILIA, MODENA, ITALY AND 2CENTRE FOR REGENERATIVE MEDICINE, “STEFANO FERRARI” UNIVERSITY OF MODENA AND REGGIO EMILIA, MODENA, ITALY – BIOLOGA MOLECOLARE)
- ELISABETTA MATTIOLI (CNR INSTITUTE OF MOLECULAR GENETICS “LUIGI LUCA CAVALLI-SFORZA”, UNIT OF BOLOGNA, BOLOGNA, ITALY AND IRCCS ISTITUTO ORTOPEDICO RIZZOLI, BOLOGNA, ITALY – BIOLOGA CELLULARE)
- ELISA SCHENA (CNR INSTITUTE OF MOLECULAR GENETICS “LUIGI LUCA CAVALLI-SFORZA”, UNIT OF BOLOGNA, BOLOGNA, ITALY AND IRCCS ISTITUTO ORTOPEDICO RIZZOLI, BOLOGNA, ITALY – BIOLOGA CELLULARE)
- SILVIA BONANNO (IRCCS “CARLO BESTA” NEUROLOGIC INSTITUTE, MILAN, ITALY – NEUROLOGA)
- PAOLA CAVALCANTE (IRCCS “CARLO BESTA” NEUROLOGIC INSTITUTE, MILAN, ITALY – BIOLOGA)
- STEFANIA MARCUZZO (IRCCS “CARLO BESTA” NEUROLOGIC INSTITUTE, MILAN, ITALY – NEUROBIOLOGA)
- CLAUDIA MALACARNE (IRCCS “CARLO BESTA” NEUROLOGIC INSTITUTE, MILAN, ITALY – DOTTORANDA IN NEUROSCIENZE)
- LORENZO MAGGI (IRCCS “CARLO BESTA” NEUROLOGIC INSTITUTE, MILAN, ITALY – NEUROLOGO)
- MELANIA GIANNOTTA (IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE, BOLOGNA, ITALY – NEUROLOGA)
- ANTONELLA PINI (IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE, BOLOGNA, ITALY – NEUROPSICHIATRA INFANTILE)
- CHIARA FIORILLO (CHILD NEUROPSYCHIATRY – IRCCS G.GASLINI UNIVERSITY OF GENOVA, GENOVA, ITALY – NEUROLOGA)
- ROBERTA RONCARATI (CNR INSTITUTE OF MOLECULAR GENETICS “LUIGI LUCA CAVALLI-SFORZA”, UNIT OF BOLOGNA, BOLOGNA, ITALY AND IRCCS ISTITUTO ORTOPEDICO RIZZOLI, BOLOGNA, ITALY – BIOLOGA)
- GAETANO VATTEMI (DEPT. OF NEUROSCIENCES, BIOMEDICINE AND MOVEMENT SCIENCES, UNIVERSITY OF VERONA, VERONA, ITALY – NEUROLOGO)
- Denise Cassandrini (IRCCS Fondazione Stella Maris, Pisa, Italy – BIOLOGA)
- Giulia Ricci (Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Pisa, Italy – NEUROLOGO)
- Gabriele Vadi (Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Pisa, Italy – MEUROLOGO)
- Gabriele Siciliano (Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Pisa, Italy – NEUROLOGO)
- Alessandra Recchia (DEPT. OF LIFE SCIENCES, UNIVERSITY OF MODENA AND REGGIO EMILIA, MODENA, ITALY AND 2CENTRE FOR REGENERATIVE MEDICINE, “STEFANO FERRARI” UNIVERSITY OF MODENA AND REGGIO EMILIA, MODENA, ITALY – BIOLOGA MOLECOLARE – GENETISTA)
- Giovanna Lattanzi (CNR INSTITUTE OF MOLECULAR GENETICS “LUIGI LUCA CAVALLI-SFORZA”, UNIT OF BOLOGNA, BOLOGNA, ITALY and IRCCS ISTITUTO ORTOPEDICO RIZZOLI, BOLOGNA, ITALY – BIOLOGA)
Presentatore
GIOVANNA LATTANZI
Modalità
Oral Communication
Abstract
Muscular laminopathies are caused by mutations in LMNA, EMD, SUN1, SUN2, SYNE1 or SYNE2 genes encoding for nuclear envelope proteins. The diseases are characterized by joint contractures, muscle weakening and wasting and heart conduction defects associated with dilated cardiomyopathy. In most cases, patients’ cell nuclei feature nuclear lamina defects, including altered prelamin A levels, and focal heterochromatin loss. However, specific biomarkers and therapeutic targets have not been identified for muscular laminopathies. Here, we identified a micro-RNA signature and three muscle-specific micro-RNAs as potential biomarkers of EDMD1 by demonstrating their altered regulation in cell cultures from patients carrying null mutations in the EMD gene and rescue in cells subjected to base editing of the mutated sequence. The affected miRNAs are targets of TGF-beta signaling and converge towards a profibrotic pathway. Accordingly, we explored levels of collagen I and ED-fibronectin in fibroblasts from laminopathic patients carrying EMD, LMNA or SYNE1 or SYNE2 mutations. This study shows the potential of CRISPR/Cas edited cells as a tool to identify biomarkers of muscular dystrophy. Our results also provide a proof of principle of the application of gene editing to treat EDMD patients.