Long-Term Outcome and Risk Stratification in Dilated Cardiolaminopathies
Michele Pasotti, MD*,
Catherine Klersy, MD ,
Andrea Pilotto, BS*,
Nicola Marziliano, PhD*,
Claudio Rapezzi, MD,
Alessandra Serio, MD*,
Savina Mannarino, MD*,
Fabiana Gambarin, MD*,
Valentina Favalli, BME*,
Maurizia Grasso, PhD*,
Manuela Agozzino, MD*,
Carlo Campana, MD ,
Antonello Gavazzi, MD||,
Oreste Febo, MD¶,
Massimiliano Marini, MD#,
Maurizio Landolina, MD,
Andrea Mortara, MD**,
Giovanni Piccolo, MD,
Mario Viganò, MD ,
Luigi Tavazzi, MD and
Eloisa Arbustini, MD*,*
* Centre for Inherited Cardiovascular Diseases, Molecular Diagnostic Laboratory, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Department of Biometry and Clinical Epidemiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Department of Cardiac Surgery, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
|| Cardiology Department, Ospedali Riuniti di Bergamo, Italy
¶ Cardiology Department, IRCCS Fondazione Salvatore Maugeri, Montescano, Italy
# Cardiology Department, Ospedale Santa Chiara di Trento, Trento, Italy
** Cardiology Department, Policlinico di Monza, Monza, Italy
Institute of Cardiology, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy
Neurology Department, IRCCS Fondazione Mondino, Pavia, Italy
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Figure 1 Position of LMNA Gene Mutations
The position of lamin A/C (LMNA) gene mutations are shown according to the nuclear localization signal (NLS) that spans residues 416 to 423: the region upstream of the NLS encodes the central alpha-helical rod domain, and the region downstream of the NLS encodes the homology box, including the beta-immunoglobulin–like fold and a deoxyribonucleic acid binding region. In red, we show missense, insertions/deletions, and stop mutations; in blue, intervening sequence mutations. The 3-dimensional reconstruction of the LMNA/C protein was made using Cn3D software, version 4.1, by loading the 2 sequence proteins NP733821 and NP005563; in particular, the illustration emphasizes the rod domain (green worms) and the globular domain (brown and light blue worms) with respect to the NLS sequence.
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Figure 2 Age-Related Penetrance of Phenotypes in Patients With LMNA Gene Mutations
The age-related penetrance of the phenotypes in patients with lamin A/C (LMNA) gene mutations is shown (test for trend p < 0.001). CI = confidence interval.
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Figure 3 Kaplan-Meier Event-Free Survival
Kaplan-Meier event-free survival stratified by 2 independent risk factors (RF): New York Heart Association functional class III to IV and competitive sports.
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Figure 4 Kaplan-Meier SCD Event-Free Survival
Kaplan-Meier sudden cardiac death (SCD) event-free survival stratified by 2 independent risk factors (RF): splicing mutations and competitive sports.
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