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

Jodi Warman Chardon; A C Smith; J Woulfe; E Pena; K Rakhra; C Dennie; C Beaulieu; Lijia Huang; J Schwartzentruber; C Hawkins; M B Harms; S Dojeiji; M Zhang; FORGE Canada Consortium; J Majewski; D E Bulman; K M Boycott; D A Dyment

doi:10.1111/cge.12561

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.

Authors

Jodi Warman Chardon^{1

2}, A C Smith³, J Woulfe^{4

2}, E Pena⁵, K Rakhra^{2

5}, C Dennie^{2

5

6}, C Beaulieu³, Lijia Huang³, J Schwartzentruber⁷, C Hawkins⁸, M B Harms⁹, S Dojeiji¹⁰, M Zhang²; FORGE Canada Consortium; J Majewski¹¹, D E Bulman^{3

12}, K M Boycott^{1

3}, D A Dyment^{1

3}

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.

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*

Substances

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

Grants and funding

Canadian Institutes of Health Research/Canada