Lamin A/C mutation affecting primarily the right side of the heart

  • Laura Ollila | laurahupa@gmail.com Helsinki University Hospital, Department of Cardiology, Helsinki, Finland.
  • Johanna Kuusisto University of Tampere, Tampere, Finland.
  • Keijo Peuhkurinen University of Tampere, Tampere, Finland.
  • Satu Kärkkäinen University of Tampere, Tampere, Finland.
  • Petri Tuomainen University of Tampere, Tampere, Finland.
  • Maija Kaartinen Helsinki University Hospital, Department of Cardiology, Helsinki, Finland.
  • Olayinka Raheem Neuromuscular Research Unit, Tampere University and University Hospital, Tampere, Finland.
  • Bjarne Udd Neuromuscular Research Unit, Tampere University and University Hospital, Tampere; Folkhälsan Institute of Genetics and Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki; Neurology Department, Vaasa Central Hospital, Vaasa, Finland.
  • Jarkko Magga Oulu University Hospital, Oulu, Finland.
  • Janne Rapola Helsinki University Hospital, Department of Cardiology, Helsinki, Finland.
  • Annukka M. Lahtinen Research Programs Unit, Molecular Medicine and Department of Medicine, University of Helsinki, Helsinki, Finland.
  • Eero Lehtonen Department of Pathology, University of Helsinki; Laboratory Animal Centre, University of Helsinki, Helsinki, Finland.
  • Miia Holmström Department of Radiology, University of Helsinki and HUS Radiology (Medical Imaging Center), Helsinki, Finland.
  • Sari Kivistö Department of Radiology, University of Helsinki and HUS Radiology (Medical Imaging Center), Helsinki, Finland.
  • Elisabeth Widén Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Markku Saksa Kanta-Häme Central Hospital, Hämeenlinna, Finland.
  • Tiina Heliö Helsinki University Hospital, Department of Cardiology, Helsinki, Finland.

Abstract

LMNA mutations are amongst the most important causes of familial dilated cardiomyopathy. The most important cause of arrhythmogenic right ventricular cardiomyopathy (ARVC) is desmosomal pathology. The aim of the study was to elucidate the role of LMNA mutations among Finnish cardiomyopathy patients. We screened 135 unrelated cardiomyopathy patients for LMNA mutations. Because of unusual phenotype, two patients were screened for the known Finnish ARVC-related mutations of desmosomal genes, and their Plakophilin-2b gene was sequenced. Myocardial samples from two patients were examined by immunohistochemical plakoglobin staining and in one case by electron microscopy. We found a new LMNA mutation Phe237Ser in a family of five affected members with a cardiomyopathy affecting primarily the right side of the heart. The phenotype resembles ARVC but does not fulfill the Task Force Criteria. The main clinical manifestations of the mutation were severe tricuspid insufficiency, right ventricular enlargement and failure. Three of the affected patients died of the heart disease, and the two living patients received heart transplants at ages 44 and 47. Electron microscopy showed nuclear blebbing compatible with laminopathy. Immunohisto - chemical analysis did not suggest desmosomal pathology. No desmosomal mutations were found. The Phe237Ser LMNA mutation causes a phenotype different from traditional cardiolaminopathy. Our findings suggest that cardiomyopathy affecting primarily the right side of the heart is not always caused by desmosomal pathology. Our observations highlight the challenges in classifying cardiomyopathies, as there often is significant overlap between the traditional categories.

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Published
2013-04-15
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Original Articles
Supporting Agencies
Finnish Foundation for Cardiovascular Research, Finnish Medical Foundation, Special governmental subsidy for health sciences research, EVO-funds, Finnish Cultural Foundation
Keywords:
LMNA, Lamin A/C, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy.
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How to Cite
Ollila, L., Kuusisto, J., Peuhkurinen, K., Kärkkäinen, S., Tuomainen, P., Kaartinen, M., Raheem, O., Udd, B., Magga, J., Rapola, J., Lahtinen, A., Lehtonen, E., Holmström, M., Kivistö, S., Widén, E., Saksa, M., & Heliö, T. (2013). Lamin A/C mutation affecting primarily the right side of the heart. Cardiogenetics, 3(1), e1. https://doi.org/10.4081/cardiogenetics.2013.e1