LIMS2 mutations are associated with a novel muscular dystrophy, severe cardiomyopathy and triangular tongues

Clin Genet. 2015 Dec;88(6):558-64. doi: 10.1111/cge.12561. Epub 2015 Feb 26.


Limb girdle muscular dystrophy (LGMD) is a heterogeneous group of genetic disorders leading to progressive muscle degeneration and often associated with cardiac complications. We present two adult siblings with childhood-onset of weakness progressing to a severe quadriparesis with the additional features of triangular tongues and biventricular cardiac dysfunction. Whole exome sequencing identified compound heterozygous missense mutations that are predicted to be pathogenic in LIMS2. Biopsy of skeletal muscle demonstrated disrupted immunostaining of LIMS2. This is the first report of mutations in LIMS2 and resulting disruption of the integrin linked kinase (ILK)-LIMS-parvin complex associated with LGMD.

Keywords: LIMS2; cardiomyopathy; exome sequencing; limb girdle muscular dystrophy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Base Sequence
  • Cardiomyopathies / genetics*
  • Cardiomyopathies / pathology
  • Exome / genetics
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Heterozygote
  • Humans
  • LIM Domain Proteins / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Muscular Dystrophies, Limb-Girdle / genetics*
  • Mutation, Missense*
  • Pedigree
  • Sequence Analysis, DNA
  • Severity of Illness Index
  • Siblings
  • Tongue / abnormalities*


  • Adaptor Proteins, Signal Transducing
  • LIM Domain Proteins
  • LIMS2 protein, human
  • Membrane Proteins