Lamin and the heart

Gabriella Captur, Eloisa Arbustini, Gisèle Bonne, Petros Syrris, Kevin Mills, Karim Wahbi, Saidi A. Mohiddin, William J. McKenna, Stephen Pettit, Carolyn Y. Ho, Antoine Muchir, Paul Gissen, Perry M. Elliott, James C. Moon

Research output: Contribution to journalReview article

23 Citations (Scopus)

Abstract

Lamins A and C are intermediate filament nuclear envelope proteins encoded by the LMNA gene. Mutations in LMNA cause autosomal dominant severe heart disease, accounting for 10% of dilated cardiomyopathy (DCM). Characterised by progressive conduction system disease, arrhythmia and systolic impairment, lamin A/C heart disease is more malignant than other common DCMs due to high event rates even when the left ventricular impairment is mild. It has several phenotypic mimics, but overall it is likely to be an under-recognised cause of DCM. In certain clinical scenarios, particularly familial DCM with early conduction disease, the pretest probability of finding an LMNA mutation may be quite high. Recognising lamin A/C heart disease is important because implantable cardioverter defibrillators need to be implanted early. Promising oral drug therapies are within reach thanks to research into the mitogen-activated protein kinase (MAPK) and affiliated pathways. Personalised heart failure therapy may soon become feasible for LMNA, alongside personalised risk stratification, as variant-related differences in phenotype severity and clinical course are being steadily elucidated. Genotyping and family screening are clinically important both to confirm and to exclude LMNA mutations, but it is the three-pronged integration of such genetic information with functional data from in vivo cardiomyocyte mechanics, and pathological data from microscopy of the nuclear envelope, that is properly reshaping our LMNA knowledge base, one variant at a time. This review explains the biology of lamin A/C heart disease (genetics, structure and function of lamins), clinical presentation (diagnostic pointers, electrocardiographic and imaging features), aspects of screening and management, including current uncertainties, and future directions.

Original languageEnglish
Pages (from-to)468-479
Number of pages12
JournalHeart
Volume104
Issue number6
DOIs
Publication statusPublished - Mar 1 2018

Fingerprint

Lamins
Lamin Type A
Heart Diseases
Nuclear Envelope
Dilated Cardiomyopathy
Mutation
Intermediate Filament Proteins
Knowledge Bases
Implantable Defibrillators
Genetic Structures
Nuclear Proteins
Mitogen-Activated Protein Kinases
Mechanics
Cardiac Myocytes
Uncertainty
Cardiac Arrhythmias
Microscopy
Heart Failure
Phenotype
Drug Therapy

Keywords

  • advanced cardiac imaging
  • cardiac imaging and diagnostics
  • cardiac magnetic resonance (cmr) imaging
  • heart transplantation
  • implanted cardiac defibrillators

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Captur, G., Arbustini, E., Bonne, G., Syrris, P., Mills, K., Wahbi, K., ... Moon, J. C. (2018). Lamin and the heart. Heart, 104(6), 468-479. https://doi.org/10.1136/heartjnl-2017-312338

Lamin and the heart. / Captur, Gabriella; Arbustini, Eloisa; Bonne, Gisèle; Syrris, Petros; Mills, Kevin; Wahbi, Karim; Mohiddin, Saidi A.; McKenna, William J.; Pettit, Stephen; Ho, Carolyn Y.; Muchir, Antoine; Gissen, Paul; Elliott, Perry M.; Moon, James C.

In: Heart, Vol. 104, No. 6, 01.03.2018, p. 468-479.

Research output: Contribution to journalReview article

Captur, G, Arbustini, E, Bonne, G, Syrris, P, Mills, K, Wahbi, K, Mohiddin, SA, McKenna, WJ, Pettit, S, Ho, CY, Muchir, A, Gissen, P, Elliott, PM & Moon, JC 2018, 'Lamin and the heart', Heart, vol. 104, no. 6, pp. 468-479. https://doi.org/10.1136/heartjnl-2017-312338
Captur G, Arbustini E, Bonne G, Syrris P, Mills K, Wahbi K et al. Lamin and the heart. Heart. 2018 Mar 1;104(6):468-479. https://doi.org/10.1136/heartjnl-2017-312338
Captur, Gabriella ; Arbustini, Eloisa ; Bonne, Gisèle ; Syrris, Petros ; Mills, Kevin ; Wahbi, Karim ; Mohiddin, Saidi A. ; McKenna, William J. ; Pettit, Stephen ; Ho, Carolyn Y. ; Muchir, Antoine ; Gissen, Paul ; Elliott, Perry M. ; Moon, James C. / Lamin and the heart. In: Heart. 2018 ; Vol. 104, No. 6. pp. 468-479.
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