Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy

Am J Hum Genet. 2000 Apr;66(4):1407-12. doi: 10.1086/302869. Epub 2000 Mar 16.


Emery-Dreifuss muscular dystrophy (EMD) is a condition characterized by the clinical triad of early-onset contractures, progressive weakness in humeroperoneal muscles, and cardiomyopathy with conduction block. The disease was described for the first time as an X-linked muscular dystrophy, but autosomal dominant and autosomal recessive forms were reported. The genes for X-linked EMD and autosomal dominant EMD (AD-EMD) were identified. We report here that heterozygote mutations in LMNA, the gene for AD-EMD, may cause diverse phenotypes ranging from typical EMD to no phenotypic effect. Our results show that LMNA mutations are also responsible for the recessive form of the disease. Our results give further support to the notion that different genetic forms of EMD have a common pathophysiological background. The distribution of the mutations in AD-EMD patients (in the tail and in the 2A rod domain) suggests that unique interactions between lamin A/C and other nuclear components exist that have an important role in cardiac and skeletal muscle function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Substitution / genetics
  • Base Sequence
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Genes, Dominant / genetics
  • Genes, Recessive / genetics
  • Genetic Predisposition to Disease / genetics
  • Heterozygote
  • Humans
  • Infant
  • Laminin / chemistry
  • Laminin / genetics*
  • Laminin / metabolism
  • Male
  • Middle Aged
  • Muscular Dystrophy, Emery-Dreifuss / genetics*
  • Muscular Dystrophy, Emery-Dreifuss / metabolism
  • Muscular Dystrophy, Emery-Dreifuss / physiopathology
  • Mutation / genetics*
  • Pedigree
  • Penetrance
  • Polymorphism, Single-Stranded Conformational
  • Protein Structure, Tertiary


  • Laminin
  • laminin A