Nature Communications (May 2019)
The K219T-Lamin mutation induces conduction defects through epigenetic inhibition of SCN5A in human cardiac laminopathy
- Nicolò Salvarani,
- Silvia Crasto,
- Michele Miragoli,
- Alessandro Bertero,
- Marianna Paulis,
- Paolo Kunderfranco,
- Simone Serio,
- Alberto Forni,
- Carla Lucarelli,
- Matteo Dal Ferro,
- Veronica Larcher,
- Gianfranco Sinagra,
- Paolo Vezzoni,
- Charles E. Murry,
- Giuseppe Faggian,
- Gianluigi Condorelli,
- Elisa Di Pasquale
Affiliations
- Nicolò Salvarani
- Institute of Genetic and Biomedical Research (IRGB), UOS of Milan, National Research Council of Italy
- Silvia Crasto
- Institute of Genetic and Biomedical Research (IRGB), UOS of Milan, National Research Council of Italy
- Michele Miragoli
- Institute of Genetic and Biomedical Research (IRGB), UOS of Milan, National Research Council of Italy
- Alessandro Bertero
- Institute for Stem Cell and Regenerative Medicine, University of Washington
- Marianna Paulis
- Institute of Genetic and Biomedical Research (IRGB), UOS of Milan, National Research Council of Italy
- Paolo Kunderfranco
- Department of Cardiovascular Medicine and Laboratory of Medical Biotechnology, Humanitas Clinical and Research Center – IRCCS
- Simone Serio
- Department of Cardiovascular Medicine and Laboratory of Medical Biotechnology, Humanitas Clinical and Research Center – IRCCS
- Alberto Forni
- Division of Cardiac Surgery, University of Verona
- Carla Lucarelli
- Division of Cardiac Surgery, University of Verona
- Matteo Dal Ferro
- Cardiovascular Department, “Ospedali Riuniti” and University of Trieste
- Veronica Larcher
- Department of Cardiovascular Medicine and Laboratory of Medical Biotechnology, Humanitas Clinical and Research Center – IRCCS
- Gianfranco Sinagra
- Cardiovascular Department, “Ospedali Riuniti” and University of Trieste
- Paolo Vezzoni
- Institute of Genetic and Biomedical Research (IRGB), UOS of Milan, National Research Council of Italy
- Charles E. Murry
- Institute for Stem Cell and Regenerative Medicine, University of Washington
- Giuseppe Faggian
- Division of Cardiac Surgery, University of Verona
- Gianluigi Condorelli
- Institute of Genetic and Biomedical Research (IRGB), UOS of Milan, National Research Council of Italy
- Elisa Di Pasquale
- Institute of Genetic and Biomedical Research (IRGB), UOS of Milan, National Research Council of Italy
- DOI
- https://doi.org/10.1038/s41467-019-09929-w
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 16
Abstract
Mutation of LMNA, encoding Lamin A/C nuclear proteins, cause dilated cardiomyopathy and conduction disorders. Here, the authors show that patient-specific iPSC-derived CMs carrying the K219T LMNA mutation have downregulated Nav1.5 channels due to dynamic cooperation of Lamin A/C and Polycomb repressor complex 2 at the SCN5A promoter.
