title: A novel lamin A/C mutation in a family with dilated cardiomyopathy, prominent conduction system disease, and need for permanent pacemaker implantation.
abstract: BACKGROUND
  The LMNA gene, which encodes the nuclear envelope protein lamin A/C, is thought to be the most common of 8 autosomal disease genes implicated in familial dilated cardiomyopathy (FDC). Each family reported to date has a unique mutation and variable degrees of cardiac conduction system, dilated cardiomyopathy, or skeletal muscle disease.
  
  
  RESULTS
  Coding regions of the LMNA gene were screened in 12 biological members of a family with dilated cardiomyopathy and conduction system disease. A novel missense mutation (Leu215Pro) in exon 4 was identified in 8 subjects. Disease was manifested as brady- and tachyarrhythmias, often necessitating permanent pacemaker implantation, and later onset of dilated cardiomyopathy and heart failure. No features of skeletal muscle disease were noted. The high percentage of affected individuals who needed pacemaker therapy (88%) was a unique characteristic of this family compared with other FDC families with LMNA mutations.
  
  
  CONCLUSIONS
  Careful examination of clinical data in families with FDC and LMNA mutations may reveal subtle genotype-phenotype correlations. Knowledge of such correlations may help to further define the mechanisms of disease in LMNA-associated FDC and can assist in the monitoring of disease for at-risk family members.
authors.affiliation: Department of Medicine, Oregon Health and Science University, Portland, Ore 97201, USA. hershber@ohsu.edu
authors.forename: Ray E
authors.initials: RE
authors.lastname: Hershberger
authors.forename: Emily L
authors.initials: EL
authors.lastname: Hanson
authors.forename: Petra M
authors.initials: PM
authors.lastname: Jakobs
authors.forename: Hugh
authors.initials: H
authors.lastname: Keegan
authors.forename: Kelly
authors.initials: K
authors.lastname: Coates
authors.forename: Sylvia
authors.initials: S
authors.lastname: Bousman
authors.forename: Michael
authors.initials: M
authors.lastname: Litt
mesh_terms: D000328:Adult; D001145:Arrhythmias, Cardiac / Q000150:complications* / Q000235:genetics* / Q000601:surgery; D002311:Cardiomyopathy, Dilated / Q000150:complications* / Q000235:genetics* / Q000601:surgery; D005260:Female; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010138:Pacemaker, Artificial; D010375:Pedigree; D010641:Phenotype
chemical_list: D034904:Lamin Type A; C440308:lamin C