title: Electrophysiological and histopathological characteristics of progressive atrioventricular block accompanied by familial dilated cardiomyopathy caused by a novel mutation of lamin A/C gene.
abstract: Conduction defect caused by lamin A/C gene mutation.
  
  
  BACKGROUND
  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.
  
  
  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 >or=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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Otomo
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
authors.forename: Tomoko
authors.initials: T
authors.lastname: Shiba
authors.forename: Akihiko
authors.initials: A
authors.lastname: Karibe
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shinozaki
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yagi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Naganuma
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tezuka
authors.forename: Masaetsu
authors.initials: M
authors.lastname: Miura
authors.forename: Meiichi
authors.initials: M
authors.lastname: Ito
authors.forename: Jun
authors.initials: J
authors.lastname: Watanabe
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Kunio
authors.initials: K
authors.lastname: Shirato
mesh_terms: D000328:Adult; D001283:Atrioventricular Node / Q000473:pathology; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000235:genetics*; D004594:Electrophysiology; D006327:Heart Block / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009206:Myocardium / Q000473:pathology; D010138:Pacemaker, Artificial
chemical_list: D034904:Lamin Type A; C440308:lamin C