Quantitative expression of the mutated lamin A/C gene in patients with cardiolaminopathy

Nupoor Narula, Valentina Favalli, Paolo Tarantino, Maurizia Grasso, Andrea Pilotto, Riccardo Bellazzi, Alessandra Serio, Fabiana I. Gambarin, Philippe Charron, Benjamin Meder, Yigal Pinto, Perry M. Elliott, Jens Mogensen, Martino Bolognesi, Michela Bollati, Eloisa Arbustini

Research output: Contribution to journalArticlepeer-review


Objectives: The authors sought to investigate the gene and protein expression in Lamin A/C (LMNA)-mutated dilated cardiolaminopathy (DCM) patients (DCMLMNAMut) versus LMNA-wild-type DCM (DCMLMNAWT), and normal controls (CTRLLMNAWT). Background: Dilated cardiolaminopathies are clinically characterized by high arrhythmogenic risk and caused by LMNA mutations. Little is known regarding quantitative gene expression (QGE) of the LMNA gene in blood and myocardium, as well as regarding myocardial expression of the lamin A/C protein. Methods: Using the comparative ΔΔCT method, we evaluated the QGE of LMNA (QGELMNA) in peripheral blood and myocardial RNA from carriers of LMNA mutations, versus blood and myocardial samples from DCMLMNAWT patients and CTRLLMNAWT individuals. After generating reference values in normal controls, QGE LMNA was performed in 311 consecutive patients and relatives, blind to genotype, to assess the predictive value of QGELMNA for the identification of mutation carriers. In parallel, Lamin A/C was investigated in myocardial samples from DCMLMNAMut versus DCMLMNAWT versus normal hearts (CTRLLMNAWT). Results: LMNA was significantly underexpressed in mRNA from peripheral blood and myocardium of DCM LMNAMut patients versus DCMLMNAWT and CTRL LMNAWT. In 311 individuals, blind to genotype, the QGELMNA showed 100% sensitivity and 87% specificity as a predictor of LMNA mutations. The receiver-operating characteristic curve analysis yielded an area under the curve of 0.957 (p <0.001). Loss of protein in cardiomyocytes' nuclei was documented in DCMLMNAMut patients. Conclusions: The reduced expression of LMNA gene in blood is a novel potential predictive biomarker for dilated cardiolaminopathies with parallel loss of protein expression in cardiomyocyte nuclei.

Original languageEnglish
Pages (from-to)1916-1920
Number of pages5
JournalJournal of the American College of Cardiology
Issue number19
Publication statusPublished - Nov 6 2012


  • biomarker
  • cardiolaminopathy
  • immunohistochemistry
  • lamin A/C
  • quantitative gene expressions

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Quantitative expression of the mutated lamin A/C gene in patients with cardiolaminopathy'. Together they form a unique fingerprint.

Cite this