Mutation update on the CHD7 gene involved in CHARGE syndrome

Authors

  • Nicole Janssen,

    1. Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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    • These authors contributed equally to this work.

  • Jorieke E. H. Bergman,

    1. Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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    • These authors contributed equally to this work.

  • Morris A. Swertz,

    1. Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
    2. Genomics Coordination Center, Groningen Bioinformatics Center, University of Groningen, Groningen, the Netherlands
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  • Lisbeth Tranebjaerg,

    1. Department of Cellular and Molecular Medicine, Wilhelm Johannsen Center for Functional Genome Research, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
    2. Department of Audiology, Bispebjerg Hospital, Copenhagen, Denmark
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  • Marianne Lodahl,

    1. Department of Cellular and Molecular Medicine, Wilhelm Johannsen Center for Functional Genome Research, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
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  • Jeroen Schoots,

    1. Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
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  • Robert M. W. Hofstra,

    1. Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands
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  • Conny M. A. van Ravenswaaij-Arts,

    Corresponding author
    1. Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
    • Department of Genetics, University of Groningen, University Medical Center Groningen, P.O. Box 30001, 9700RB Groningen, the Netherlands.
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  • Lies H. Hoefsloot

    1. Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
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  • Communicated by Mark H. Paalman

Abstract

CHD7 is a member of the chromodomain helicase DNA-binding (CHD) protein family that plays a role in transcription regulation by chromatin remodeling. Loss-of-function mutations in CHD7 are known to cause CHARGE syndrome, an autosomal-dominant malformation syndrome in which several organ systems, for example, the central nervous system, eye, ear, nose, and mediastinal organs, are variably involved. In this article, we review all the currently described CHD7 variants, including 183 new pathogenic mutations found by our laboratories. In total, we compiled 528 different pathogenic CHD7 alterations from 508 previously published patients with CHARGE syndrome and 294 unpublished patients analyzed by our laboratories. The mutations are equally distributed along the coding region of CHD7 and most are nonsense or frameshift mutations. Most mutations are unique, but we identified 94 recurrent mutations, predominantly arginine to stop codon mutations. We built a locus-specific database listing all the variants that is easily accessible at www.CHD7.org. In addition, we summarize the latest data on CHD7 expression studies, animal models, and functional studies, and we discuss the latest clinical insights into CHARGE syndrome. Hum Mutat 33:1149–1160, 2012. © 2012 Wiley Periodicals, Inc.

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