Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy

Nat Genet. 1999 Mar;21(3):285-8. doi: 10.1038/6799.


Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and a cardiomyopathy with conduction blocks which is life-threatening. Two modes of inheritance exist, X-linked (OMIM 310300) and autosomal dominant (EDMD-AD; OMIM 181350). EDMD-AD is clinically identical to the X-linked forms of the disease. Mutations in EMD, the gene encoding emerin, are responsible for the X-linked form. We have mapped the locus for EDMD-AD to an 8-cM interval on chromosome 1q11-q23 in a large French pedigree, and found that the EMD phenotype in four other small families was potentially linked to this locus. This region contains the lamin A/C gene (LMNA), a candidate gene encoding two proteins of the nuclear lamina, lamins A and C, produced by alternative splicing. We identified four mutations in LMNA that co-segregate with the disease phenotype in the five families: one nonsense mutation and three missense mutations. These results are the first identification of mutations in a component of the nuclear lamina as a cause of inherited muscle disorder. Together with mutations in EMD (refs 5,6), they underscore the potential importance of the nuclear envelope components in the pathogenesis of neuromuscular disorders.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cloning, Molecular
  • Deoxyribonuclease HpaII / genetics
  • Deoxyribonucleases, Type II Site-Specific / genetics
  • Exons
  • Female
  • Genes, Dominant
  • Haplotypes
  • Humans
  • Immunohistochemistry
  • Lamin Type A
  • Lamins
  • Male
  • Microsatellite Repeats
  • Molecular Sequence Data
  • Muscular Dystrophies / genetics*
  • Muscular Dystrophy, Emery-Dreifuss
  • Mutation*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Nuclear Proteins / analysis
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Pedigree
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid


  • Lamin Type A
  • Lamins
  • Nuclear Proteins
  • Deoxyribonuclease HpaII
  • CTAG-specific type II deoxyribonucleases
  • Deoxyribonucleases, Type II Site-Specific

Associated data

  • GENBANK/L12399
  • GENBANK/L12400
  • GENBANK/L12401
  • GENBANK/O03252
  • GENBANK/P02545
  • GENBANK/P02546
  • GENBANK/P08928
  • GENBANK/P09010
  • GENBANK/P11048
  • GENBANK/P11516
  • GENBANK/P13648
  • GENBANK/P14731
  • GENBANK/P14732
  • GENBANK/P14733
  • GENBANK/P20700
  • GENBANK/P21619
  • GENBANK/P21910
  • GENBANK/P48678
  • GENBANK/P48679

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