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Etiology of limb girdle muscular dystrophy 1D/1E determined by laser capture microdissection proteomics

Authors

  • Steven A. Greenberg MD,

    Corresponding author
    1. Department of Neurology, Division of Neuromuscular Disease, Brigham and Women's Hospital and Children's Hospital Informatics Program, Children's Hospital Boston, Harvard Medical School, Boston, MA
    • Brigham and Women's Hospital Department of Neurology, Division of Neuromuscular Disease and Children's Hospital Boston, Harvard Medical School, 75 Francis Street, Boston, MA 02115
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  • Mohammad Salajegheh MD,

    1. Department of Neurology, Division of Neuromuscular Disease, Brigham and Women's Hospital and Children's Hospital Informatics Program, Children's Hospital Boston, Harvard Medical School, Boston, MA
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  • Daniel P. Judge MD,

    1. Center for Inherited Heart Disease, Division of Cardiology, Johns Hopkins University, Baltimore, MD
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  • Matthew W. Feldman MS,

    1. Center for Inherited Heart Disease, Division of Cardiology, Johns Hopkins University, Baltimore, MD
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  • Ralph W. Kuncl PhD, MD,

    1. Departments of Neurology and Brain and Cognitive Sciences, University of Rochester School of Medicine and Dentistry, Rochester, NY
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  • Zachary Waldon BS,

    1. Proteomics Center at Children's Hospital Boston, Harvard Medical School, Boston, MA
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  • Hanno Steen PhD,

    1. Proteomics Center at Children's Hospital Boston, Harvard Medical School, Boston, MA
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  • Kathryn R. Wagner MD, PhD

    1. Center for Genetic Muscle Disorders, Kennedy Krieger Institute and Departments of Neurology and Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD
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Abstract

Limb girdle muscular dystrophy 1D/1E (OMIM nomenclature LGMD1D, Human Gene Nomenclature Committee LGMD1E), a skeletal and cardiac myopathy, has previously been linked to chromosome 6q23. We used laser capture microdissection to isolate cytoplasmic inclusions from skeletal muscle from a patient with LGMD1D/1E, performed mass spectrometry–based proteomics on these minute inclusions, and identified through bioinformatics desmin as their major constituent. Sequencing in this patient and family members identified the genetic basis of the previously reported 6q23 linked LGMD1D/1E to be due to an intron splice donor site mutation (IVS3+3A>G) of the desmin gene located on chromosome 2q35. Ann Neurol 2011

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