2. Academic Validation
  3. LIMS2 mutations are associated with a novel muscular dystrophy, severe cardiomyopathy and triangular tongues

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.
Jodi Warman Chardon 1 2,  A C Smith 3,  J Woulfe 4 2,  E Pena 5,  K Rakhra 2 5,  C Dennie 2 5 6,  C Beaulieu 3,  Lijia Huang 3,  J Schwartzentruber 7,  C Hawkins 8,  M B Harms 9,  S Dojeiji 10,  M Zhang 2,  FORGE Canada Consortium,  J Majewski 11,  D E Bulman 3 12,  K M Boycott 1 3,  D A Dyment 1 3
Affiliations

Affiliations

  • 1 Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
  • 2 Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
  • 3 Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
  • 4 Department of Pathology, The Ottawa Hospital, Ottawa, Ontario, Canada.
  • 5 Department of Medical Imaging, The Ottawa Hospital, Ottawa, Ontario, Canada.
  • 6 University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
  • 7 McGill University and Genome Quebec Innovation Center, Montreal, Quebec, Canada.
  • 8 Department of Laboratory Medicine & Pathobiology, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • 9 Department of Neurology and Hope Center for Neurological Disorders, Washington University, Saint Louis, MO, USA.
  • 10 The Ottawa Hospital Rehabilitation Center, Ottawa, Ontario, Canada.
  • 11 Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
  • 12 Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
PMID: 25589244 DOI: 10.1111/cge.12561
Abstract

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.

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