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Mosaic maternal uniparental disomy of chromosome 15 in Prader–Willi syndrome: Utility of genome-wide SNP array

Authors

  • Kosuke Izumi,

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Avni B. Santani,

    1. Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Matthew A. Deardorff,

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    2. Department of Pediatrics, the Perelman School of Medicine, the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Holly A. Feret,

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Tanya Tischler,

    1. Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Brian D. Thiel,

    1. Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Surabhi Mulchandani,

    1. Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Catherine A. Stolle,

    1. Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Nancy B. Spinner,

    1. Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    2. Department of Pediatrics, the Perelman School of Medicine, the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Elaine H. Zackai,

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    2. Department of Pediatrics, the Perelman School of Medicine, the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Laura K. Conlin

    Corresponding author
    1. Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    • Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, 3615 Civic Center Blvd., Abramson Research Building, Rm. 1007B, Philadelphia, PA 19146.
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  • How to Cite this Article: Izumi K, Santani AB, Deardorff MA, Feret HA, Tischler T, Thiel BD, Mulchandani S, Stolle CA, Spinner NB, Zackai EH, Conlin LK. 2012. Mosaic maternal uniparental disomy of chromosome 15 in Prader–Willi syndrome: Utility of genome-wide SNP array. Am J Med Genet Part A 161A:166–171.

Abstract

Prader–Willi syndrome is caused by the loss of paternal gene expression on 15q11.2–q13.2, and one of the mechanisms resulting in Prader–Willi syndrome phenotype is maternal uniparental disomy of chromosome 15. Various mechanisms including trisomy rescue, monosomy rescue, and post fertilization errors can lead to uniparental disomy, and its mechanism can be inferred from the pattern of uniparental hetero and isodisomy. Detection of a mosaic cell line provides a unique opportunity to understand the mechanism of uniparental disomy; however, mosaic uniparental disomy is a rare finding in patients with Prader–Willi syndrome. We report on two infants with Prader–Willi syndrome caused by mosaic maternal uniparental disomy 15. Patient 1 has mosaic uniparental isodisomy of the entire chromosome 15, and Patient 2 has mosaic uniparental mixed iso/heterodisomy 15. Genome-wide single-nucleotide polymorphism array was able to demonstrate the presence of chromosomally normal cell line in the Patient 1 and trisomic cell line in Patient 2, and provide the evidence that post-fertilization error and trisomy rescue as a mechanism of uniparental disomy in each case, respectively. Given its ability of detecting small percent mosaicism as well as its capability of identifying the loss of heterozygosity of chromosomal regions, genome-wide single-nucleotide polymorphism array should be utilized as an adjunct to the standard methylation analysis in the evaluation of Prader–Willi syndrome. © 2012 Wiley Periodicals, Inc.

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