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Identification of Novel Mutations Confirms PDE4D as a Major Gene Causing Acrodysostosis

Authors

  • Danielle C. Lynch,

    1. Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada
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    • These authors contributed equally to this work.

  • David A. Dyment,

    1. Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
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    • These authors contributed equally to this work.

  • Lijia Huang,

    1. Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
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  • Sarah M. Nikkel,

    1. Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
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  • Didier Lacombe,

    1. CHU de Bordeaux, Service de Génétique Médicale, Bordeaux, France
    2. Université de Bordeaux, Laboratoire Maladies Rares: Génétique et Métabolisme (MRGM), Bordeaux, France
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  • Philippe M. Campeau,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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  • Brendan Lee,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Howard Hughes Medical Institute, Houston, Texas
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  • Carlos A. Bacino,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Clinical Care Center, Texas Children's Hospital, Houston, Texas
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  • Jacques L. Michaud,

    1. Centre of Excellence in Neuromics, Université de Montréal and CHU Sainte-Justine Research Centre, Montréal, Québec, Canada
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  • Francois P. Bernier,

    1. Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada
    2. Alberta Children's Hospital Research Institute for Child and Maternal Health, University of Calgary, Calgary, Alberta, Canada
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  • FORGE Canada Consortium,

    1. Steering Committee Membership is listed in Acknowledgements
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  • Jillian S. Parboosingh,

    Corresponding author
    1. Alberta Children's Hospital Research Institute for Child and Maternal Health, University of Calgary, Calgary, Alberta, Canada
    • Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada
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  • A. Micheil Innes

    Corresponding author
    1. Alberta Children's Hospital Research Institute for Child and Maternal Health, University of Calgary, Calgary, Alberta, Canada
    • Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada
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Errata

This article is corrected by:

  1. Errata: Identification of Novel Mutations Confirms PDE4D as a Major Gene Causing Acrodysostosis Volume 34, Issue 4, 667, Article first published online: 11 February 2013

  • This article was published online on 9 November 2012. Subsequently, it was determined that the gene and protein symbols were set incorrectly, and the corrected version was published online on 11 February 2013.

  • Contract Grant sponsors: Government of Canada through Genome Canada, the Canadian Institutes of Health Research; Ontario Genomics Institute (OGI-049); Genome Quebec; Genome British Columbia; CIHR Institute of Genetics Clinical Investigatorship Award (to D.A.D.); CIHR Training program in Genetics, Child Development and Health (to D.C.L).

  • Communicated by Arnold Munnich

Correspondence to: Jillian S. Parboosingh, Dept. of Medical Genetics, 2888 Shaganappi Trail NW, Calgary, AB, T3B 6A8, Canada. E-mail: jillian.parboosingh@albertahealthservices.ca; or A. Micheil Innes, Dept. of Medical Genetics, 2888 Shaganappi Trail NW, Calgary, AB, T3B 6A8, Canada. E-mail: micheil.innes@albertahealthservices.ca

ABSTRACT

Acrodysostosis is characterized by nasal hypoplasia, peripheral dysostosis, variable short stature, and intellectual impairment. Recently, mutations in PRKAR1A were reported in patients with acrodysostosis and hormone resistance. Subsequently, mutations in a phosphodiesterase gene (PDE4D) were identified in seven sporadic cases. We sequenced PDE4D in seven acrodysostosis patients from five families. Missense mutations were identified in all cases. Families showed de novo inheritance except one family with three affected children whose father was subsequently found to have subtle features of acrodysostosis. There were no recurrent mutations. Short stature and endocrine resistance are rare in this series; however, cognitive involvement and obesity were frequent. This last finding is relevant given PDE4D is insulin responsive and potentially involved in lipolysis. PDE4D encodes a cyclic AMP regulator and places PDE4D-related acrodysostosis within the same family of diseases as pseudohypoparathyroidism, pseudopseudohypoparathyroidism, PRKAR1A-related acrodysostosis and brachydactyly-mental retardation syndrome; all characterized by cognitive impairment and short distal extremities.

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