Identification of novel mutations in LMNA associated with familial forms of dilated cardiomyopathy

Genet Test Mol Biomarkers. 2012 Jun;16(6):543-9. doi: 10.1089/gtmb.2011.0214. Epub 2012 Jan 6.


The lamin A/C proteins are major structural and functional components of the nuclear lamina. Mutations identified in LMNA encoding lamin A/C belong to the most frequently described causes for inherited forms of dilated cardiomyopathy (DCM). To elucidate the clinical characteristics of LMNA mutation carriers we performed genetic analysis of LMNA in 20 unrelated patients with DCM and cardiac conduction disease. In six small nuclear families heterozygous mutations in LMNA were identified. Two missense mutations led to the substitution of highly conserved amino acid residues within the rod domain of lamin A/C and four not-yet-described nonsense mutations cause the formation of predicted truncated lamin A/C missing parts of the tail domain. DCM was the most prominent clinical characteristic of the affected family members with a high degree of involvement of conduction system defects and less often accompanied by muscular dystrophy. The cardiac phenotype of the affected family members was severe and progressive with age, indicating the necessity for a genetic testing for LMNA mutations in patients with familial DCM and early onset of conduction disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arrhythmias, Cardiac / genetics
  • Cardiomyopathy, Dilated / diagnosis
  • Cardiomyopathy, Dilated / genetics*
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Heterozygote*
  • Humans
  • Lamin Type A / chemistry
  • Lamin Type A / genetics*
  • Male
  • Mice
  • Molecular Sequence Data
  • Muscular Dystrophies / genetics
  • Mutation*
  • Mutation, Missense
  • Phenotype
  • Rats
  • Sequence Analysis, DNA


  • LMNA protein, human
  • Lamin Type A

Supplementary concepts

  • Familial dilated cardiomyopathy