Screening of DNA methylation at the H19 promoter or the distal region of its ICR1 ensures efficient detection of chromosome 11p15 epimutations in Russell–Silver syndrome

Authors

  • Shin-Ichi Horike,

    1. Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada
    2. Frontier Science Organization, Institute for Gene Research, Kanazawa University, Kanazawa, Japan
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  • Jose Carlos P. Ferreira,

    1. Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada
    2. Institute of Medical Sciences, University of Toronto, Toronto, Canada
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  • Makiko Meguro-Horike,

    1. Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada
    2. Frontier Science Organization, Institute for Gene Research, Kanazawa University, Kanazawa, Japan
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  • Sanaa Choufani,

    1. Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada
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  • Adam C. Smith,

    1. Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada
    2. Institute of Medical Sciences, University of Toronto, Toronto, Canada
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  • Cheryl Shuman,

    1. Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada
    2. Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Canada
    3. Department of Molecular Genetics, University of Toronto, Toronto, Canada
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  • Wendy Meschino,

    1. Genetics, North York General Hospital, Toronto, Canada
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  • David Chitayat,

    1. Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada
    2. Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Canada
    3. Department of Molecular Genetics, University of Toronto, Toronto, Canada
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  • Elaine Zackai,

    1. Division of Human Genetics & Molecular Biology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Stephen W. Scherer,

    1. Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada
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  • Rosanna Weksberg

    Corresponding author
    1. Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada
    2. Institute of Medical Sciences, University of Toronto, Toronto, Canada
    3. Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Canada
    4. Department of Molecular Genetics, University of Toronto, Toronto, Canada
    • Clinical and Metabolic Genetics, The Hospital for Sick Children, University Ave., Toronto, Ontario, Canada M5G 1X8.
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  • Shin-Ichi Horike and Jose Carlos P. Ferreira contributed equally to this work.

  • How to cite this article: Horike S-I, Ferreira JCP, Meguro-Horike M, Choufani S, Smith AC, Shuman C, Meschino W, Chitayat D, Zackai E, Scherer SW, Weksberg R. 2009. Screening of DNA methylation at the H19 promoter or the distal region of its ICR1 ensures efficient detection of chromosome 11p15 epimutations in Russell–Silver syndrome. Am J Med Genet Part A 149A:2415–2423.

Abstract

Over a 10-year period blood samples were collected from 57 individuals with growth restriction and RSS-like features. Our goal was to identify epigenetic abnormalities in this cohort, including uniparental disomy of chromosome 7 (UPD7), methylation changes at chromosome11p15, as well as new epigenomic alterations. We evaluated the methylation status of 7 imprinting control regions on chromosomes 7, 11, 14, and 15. UPD7 and chromosome 7 structural abnormalities had been previously identified in five patients. Epigenetic alterations on chromosome 11p15 were identified in 11 patients. Of interest, in 3 of these 11 patients, the epigenetic alterations were limited to the H19 promoter and the distal region of its associated imprinting center, ICR1. In addition, in one patient, we detected methylation changes consistent with maternal UPD at all tested imprinted regions. This patient series suggests that epimutations on chromosome 11p15 can be most efficiently detected in RSS patients by screening for DNA methylation defects at the H19 promoter or the distal region of ICR. © 2009 Wiley-Liss, Inc.

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