title: LIMS2 mutations are associated with a novel muscular dystrophy, severe cardiomyopathy and triangular tongues.
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.
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.|Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Jodi Warman
authors.initials: JW
authors.lastname: Chardon
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: A C
authors.initials: AC
authors.lastname: Smith
authors.affiliation: Department of Pathology, The Ottawa Hospital, Ottawa, Ontario, Canada.|Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Woulfe
authors.affiliation: Department of Medical Imaging, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Pena
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Medical Imaging, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Rakhra
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Medical Imaging, The Ottawa Hospital, Ottawa, Ontario, Canada.|University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Dennie
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Beaulieu
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Lijia
authors.initials: L
authors.lastname: Huang
authors.affiliation: McGill University and Genome Quebec Innovation Center, Montreal, Quebec, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Schwartzentruber
authors.affiliation: Department of Laboratory Medicine & Pathobiology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Hawkins
authors.affiliation: Department of Neurology and Hope Center for Neurological Disorders, Washington University, Saint Louis, MO, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Harms
authors.affiliation: The Ottawa Hospital Rehabilitation Center, Ottawa, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Dojeiji
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Majewski
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.|Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: D E
authors.initials: DE
authors.lastname: Bulman
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.|Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: K M
authors.initials: KM
authors.lastname: Boycott
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.|Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: D A
authors.initials: DA
authors.lastname: Dyment
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D009202:Cardiomyopathies / Q000235:genetics* / Q000473:pathology; D059472:Exome / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D035781:Siblings; D014059:Tongue / Q000002:abnormalities*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; C490235:LIMS2 protein, human; D008565:Membrane Proteins
keywords: LIMS2; cardiomyopathy; exome sequencing; limb girdle muscular dystrophy