title: Malignant mutation in the lamin A/C gene causing progressive conduction system disease and early sudden death in a family with mild form of limb-girdle muscular dystrophy.
abstract: BACKGROUND
  Lamin proteins A and C are major functional and structural components of the nuclear lamina. Mutations of the LMNA gene have been associated with dilated cardiomyopathy, conduction system defects and skeletal muscle dystrophy simultaneously, in variable involvement. We report on a family with a mutation of the lamin A/C gene (c.908-909delCT).
  
  
  METHODS
  Thirty five members of the family of a proband were studied and underwent clinical and genetic evaluation. Family members were considered to be affected if they demonstrated conduction system defects, limb-girdle muscular dystrophy, dilated cardiomyopathy, carried the lamin A/C mutation or suffered sudden death.
  
  
  RESULTS
  Fifteen members of the family were considered to be affected. Conduction system defects were the major feature of the affected members (67%), with variable involvement of dilated cardiomyopathy (33%), and limb-girdle muscular dystrophy (53%). Sudden death occurred in four members (27%) and was the presenting feature in three (20%) of the affected members at an early age. Mutation c.908-909delCT was confirmed in 12 of the affected members. The pattern of inheritance was autosomal dominant.
  
  
  CONCLUSIONS
  Lamin c.908-909delCT mutation is malignant compared to other dilated cardiomyopathy-associated mutations of the Lamin A/C gene. Patients with this mutation have rapid progression of atrioventricular conduction abnormalities, and sudden death may be the presenting feature. Early identification of affected families and consideration of an implantable defibrillator is important in this setting.
authors.affiliation: Department of Cardiology, Nicosia General Hospital, Nicosia, Cyprus.
authors.forename: Loizos
authors.initials: L
authors.lastname: Antoniades
authors.forename: Christos
authors.initials: C
authors.lastname: Eftychiou
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kyriakides
authors.forename: Kyproula
authors.initials: K
authors.lastname: Christodoulou
authors.forename: Demosthenes G
authors.initials: DG
authors.lastname: Katritsis
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D003645:Death, Sudden; D004562:Electrocardiography; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D009154:Mutation; D010641:Phenotype
chemical_list: D034904:Lamin Type A; C440308:lamin C