Large genomic deletions: A novel cause of Ullrich congenital muscular dystrophy

Authors

  • A. Reghan Foley MD,

    1. Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
    2. Dubowitz Neuromuscular Centre, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London, UK
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  • Ying Hu MS,

    1. Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
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  • Yaqun Zou MD,

    1. Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
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  • Michele Yang MD,

    1. Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
    2. Department of Pediatrics, University of Colorado Denver, Aurora, CO
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  • Līvija Medne MS, CGC,

    1. Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
    2. Division of Human Genetics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
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  • Meganne Leach MSN, CRNP,

    1. Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
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  • Laura K. Conlin PhD,

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
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  • Nancy Spinner PhD,

    1. Division of Pathology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
    2. Department of Pediatrics, University of Pennsylvania, Philadelphia, PA
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  • Tamim H. Shaikh PhD,

    1. Department of Pediatrics, University of Colorado Denver, Aurora, CO
    2. Department of Pediatrics, University of Pennsylvania, Philadelphia, PA
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  • Marni Falk MD,

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
    2. Department of Pediatrics, University of Pennsylvania, Philadelphia, PA
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  • Ann M. Neumeyer MD,

    1. Department of Neurology, Massachusetts General Hospital, Harvard University, Boston, MA
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  • Laurie Bliss,

    1. Department of Neurology, Massachusetts General Hospital, Harvard University, Boston, MA
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  • Brian S. Tseng MD, PhD,

    1. Department of Neurology, Massachusetts General Hospital, Harvard University, Boston, MA
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  • Thomas L. Winder PhD, FACMG,

    1. Prevention Genetics, Marshfield, WI
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  • Carsten G. Bönnemann MD

    Corresponding author
    1. Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
    2. Department of Pediatrics, University of Pennsylvania, Philadelphia, PA
    3. Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke/NIH, Bethesda,MD
    • Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke/NIH, Porter Neuroscience Research Center, Building 35, Room 2A-116, MSC 35 Convent Drive, Bethesda, MD 20892-3705
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Abstract

Two mutational mechanisms are known to underlie Ullrich congenital muscular dystrophy (UCMD): heterozygous dominant negatively-acting mutations and recessively-acting loss-of-function mutations. We describe large genomic deletions on chromosome 21q22.3 as a novel type of mutation underlying recessively inherited UCMD in 2 families. Clinically unaffected parents carrying large genomic deletions of COL6A1and COL6A2also provide conclusive evidence that haploinsufficiency for COL6A1and COL6A2is not a disease mechanism for Bethlem myopathy. Our findings have important implications for the genetic evaluation of patients with collagen VI–related myopathies as well as for potential therapeutic interventions for this patient population. Ann Neurol 2011;69:206–211

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