Electrophysiological and histopathological characteristics of progressive atrioventricular block accompanied by familial dilated cardiomyopathy caused by a novel mutation of lamin A/C gene

Jun Otomo, Shigeo Kure, Tomoko Shiba, Akihiko Karibe, Tsuyoshi Shinozaki, Tetsuo Yagi, Hiroshi Naganuma, Fumiaki Tezuka, Masaetsu Miura, Meiichi Ito, Jun Watanabe, Yoichi Matsubara, Kunio Shirato

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Introduction: Mutations of lamin A/C gene (LMNA) cause dilated cardiomyopathy (DCM) with atrioventricular (AV) conduction defect, although the electrophysiological and histological profiles are not fully understood. Methods and Results: We analyzed a large Japanese family (21 affected and 203 unaffected members) of DCM with AV block. The responsible LMNA mutation of IVS3-10A>G was novel and caused an aberrant splicing. The first clinical manifestation was low-grade AV block or atrial fibrillation (AF), which developed in affected members aged ≥30 years. We observed that the AV block progressed to third-degree within several years. The electrophysiological study of the four affected members revealed an impairment of intra-AV nodal conduction. Because of advanced AV block, pacemakers were implanted in 14 out of 21 affected members at the mean age of 44 years. Three affected members died suddenly and two affected members died of heart failure and/or ventricular tachycardia (VT) even after the pacemaker implantation. Postmortem examination showed conspicuous fibrofatty degeneration of the AV node. Endomyocardial biopsies showed remarkably deformed nuclei and substantial glycogen deposits in the subsarcolemma. Conclusion: The clinical phenotype in this family was characterized by (1) the first manifestation of the prolonged PQ interval or AF in adolescence, (2) progressive intra-AV nodal block to the third degree in several years, and (3) progressive heart failure after pacemaker implantation. Histological study revealed preferential degeneration at the AV node area and novel cellular damages in the working myocardium.

Original languageEnglish
Pages (from-to)137-145
Number of pages9
JournalJournal of Cardiovascular Electrophysiology
Volume16
Issue number2
DOIs
Publication statusPublished - 2005 Feb

Keywords

  • Atrial fibrillation
  • Atrioventricular block
  • Dilated cardiomyopathy
  • Gene
  • Lamin A/C

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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