Large genomic deletions: A novel cause of Ullrich congenital muscular dystrophy
A. Reghan Foley MD
Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Dubowitz Neuromuscular Centre, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London, UK
Search for more papers by this authorYing Hu MS
Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorYaqun Zou MD
Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorMichele Yang MD
Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Department of Pediatrics, University of Colorado Denver, Aurora, CO
Search for more papers by this authorLīvija Medne MS, CGC
Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Division of Human Genetics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorMeganne Leach MSN, CRNP
Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorLaura K. Conlin PhD
Division of Human Genetics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorNancy Spinner PhD
Division of Pathology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Department of Pediatrics, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorTamim H. Shaikh PhD
Department of Pediatrics, University of Pennsylvania, Philadelphia, PA
Department of Pediatrics, University of Colorado Denver, Aurora, CO
Search for more papers by this authorMarni Falk MD
Division of Human Genetics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Department of Pediatrics, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorAnn M. Neumeyer MD
Department of Neurology, Massachusetts General Hospital, Harvard University, Boston, MA
Search for more papers by this authorLaurie Bliss
Department of Neurology, Massachusetts General Hospital, Harvard University, Boston, MA
Search for more papers by this authorBrian S. Tseng MD, PhD
Department of Neurology, Massachusetts General Hospital, Harvard University, Boston, MA
Search for more papers by this authorThomas L. Winder PhD, FACMG
Prevention Genetics, Marshfield, WI
Search for more papers by this authorCorresponding Author
Carsten G. Bönnemann MD
Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Department of Pediatrics, University of Pennsylvania, Philadelphia, PA
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 20892-3705Search for more papers by this authorA. Reghan Foley MD
Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Dubowitz Neuromuscular Centre, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London, UK
Search for more papers by this authorYing Hu MS
Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorYaqun Zou MD
Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorMichele Yang MD
Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Department of Pediatrics, University of Colorado Denver, Aurora, CO
Search for more papers by this authorLīvija Medne MS, CGC
Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Division of Human Genetics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorMeganne Leach MSN, CRNP
Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorLaura K. Conlin PhD
Division of Human Genetics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorNancy Spinner PhD
Division of Pathology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Department of Pediatrics, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorTamim H. Shaikh PhD
Department of Pediatrics, University of Pennsylvania, Philadelphia, PA
Department of Pediatrics, University of Colorado Denver, Aurora, CO
Search for more papers by this authorMarni Falk MD
Division of Human Genetics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Department of Pediatrics, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorAnn M. Neumeyer MD
Department of Neurology, Massachusetts General Hospital, Harvard University, Boston, MA
Search for more papers by this authorLaurie Bliss
Department of Neurology, Massachusetts General Hospital, Harvard University, Boston, MA
Search for more papers by this authorBrian S. Tseng MD, PhD
Department of Neurology, Massachusetts General Hospital, Harvard University, Boston, MA
Search for more papers by this authorThomas L. Winder PhD, FACMG
Prevention Genetics, Marshfield, WI
Search for more papers by this authorCorresponding Author
Carsten G. Bönnemann MD
Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Department of Pediatrics, University of Pennsylvania, Philadelphia, PA
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 20892-3705Search for more papers by this authorAbstract
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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