Autosomal recessive Emery-Dreifuss muscular dystrophy caused by a novel mutation (R225Q) in the lamin A/C gene identified by exome sequencing

Muscle Nerve. 2012 Apr;45(4):605-10. doi: 10.1002/mus.22324.


Introduction: The aim of this study is to describe a new mutation in the LMNA gene diagnosed by whole exome sequencing.

Methods: A two-generation kindred with recessive limb-girdle muscular dystrophy was evaluated by exome sequencing of the proband's DNA.

Results: Exome sequencing disclosed 194,618 variants (170,196 SNPs, 8482 MNPs, 7466 insertions, 8307 deletions, and 167 mixed combinations); 71,328 were homozygotic and 123,290 were heterozygotic, with 11,753 non-synonymous, stop-gain, stop-loss, or frameshift mutations occurring in the coding region or nearby intronic region. The cross-referencing of these mutations in candidate genes for muscular dystrophy showed a homozygote mutation c.G674A in exon 4 of LMNA causing a protein change R225Q in an arginine conserved from human to Xenopus tropicalis and in lamin B1.

Conclusions: This technique will be preferred for studying patients with muscular dystrophy in the coming years.

Publication types

  • Case Reports

MeSH terms

  • Age of Onset
  • Animals
  • Biopsy
  • Creatine Kinase / blood
  • Diplopia / etiology
  • Disease Progression
  • Exome / genetics
  • Female
  • Frameshift Mutation
  • Gait Disorders, Neurologic / etiology
  • Heart Diseases / etiology
  • Humans
  • Lamin Type A / genetics*
  • Middle Aged
  • Molecular Sequence Data
  • Muscle, Skeletal / physiology
  • Muscular Dystrophy, Emery-Dreifuss / diagnosis*
  • Muscular Dystrophy, Emery-Dreifuss / genetics*
  • Muscular Dystrophy, Emery-Dreifuss / pathology
  • Mutation / genetics
  • Mutation / physiology
  • Pedigree
  • Sequence Analysis, DNA
  • Xenopus / genetics


  • LMNA protein, human
  • Lamin Type A
  • Creatine Kinase