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Myoclonus-dystonia and Silver–Russell syndrome resulting from maternal uniparental disomy of chromosome 7

Authors

  • MB Sheridan,

    1. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • A Bytyci Telegrafi,

    1. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • V Stinnett,

    1. Cytogenetics and Microarray Laboratory, Kennedy Krieger Institute, Baltimore, MD, USA
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  • CC Umeh,

    1. Department of Neurology
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  • Z Mari,

    1. Department of Neurology
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  • TM Dawson,

    1. Department of Neurology
    2. Neuroregeneration Program, Institute for Cell Engineering and the Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • J Bodurtha,

    1. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • DAS Batista

    Corresponding author
    1. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    2. Cytogenetics and Microarray Laboratory, Kennedy Krieger Institute, Baltimore, MD, USA
    3. Department of Pathology, Johns Hopkins University, Baltimore, MD, USA
    • Corresponding author: Denise A.S. Batista, PhD, Cytogenetics Laboratory, Johns Hopkins University, 600 N. Wolfe St., Park Bldg. SB 202, Baltimore, MD 21287, USA.

      Tel.: +1 410 955 8363;

      fax: +1 410 614 7440;

      e-mail: dbatist1@jhmi.edu

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  • The authors confirm that there are no potential conflicts of interest with this manuscript.

Abstract

Myoclonus-dystonia (M-D) is a movement disorder that is often associated with mutations in epsilon-sarcoglycan (SGCE), a maternally imprinted gene at 7q21.3. We report a 24-year-old male with short stature (<5th percentile) and a movement disorder clinically consistent with M-D. Single nucleotide polymorphism (SNP) array did not identify significant copy number changes, but revealed three long continuous stretches of homozygosity on chromosome 7 suggestive of uniparental disomy. Parental SNP arrays confirmed that the proband had maternal uniparental disomy of chromosome 7 (mUPD7) with regions of heterodisomy and isodisomy. mUPD7 is the cause of approximately 5–10% of Silver–Russell syndrome (SRS), a disorder characterized by prenatal and postnatal growth retardation. Although SRS was not suspected in our patient, these findings explain his short stature. SGCE methylation testing showed loss of the unmethylated paternal allele. Our findings provide a unifying diagnosis for his short stature and M-D and help to optimize his medication regimen. In conclusion, we show that M-D is a clinical feature that may be associated with SRS due to mUPD7. Individuals with mUPD7 should be monitored for the development of movement disorders. Conversely, individuals with M-D and short stature should be evaluated for SRS.

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