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Utility of SNP arrays in detecting, quantifying, and determining meiotic origin of tetrasomy 12p in blood from individuals with Pallister–Killian syndrome

Authors

  • Laura K. Conlin,

    Corresponding author
    1. Department of Pathology, 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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  • Maninder Kaur,

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Kosuke Izumi,

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Lindsey Campbell,

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Alisha Wilkens,

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Dinah Clark,

    1. Division of Human Genetics, 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. The Perelman School of Medicine at 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. The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pennsylvania
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  • Phillip Pallister,

    1. Shodair, Helena, Montana
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  • Hakon Hakonarson,

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    2. The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pennsylvania
    3. The Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Nancy B. Spinner,

    1. Department of Pathology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    2. The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pennsylvania
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  • Ian D. Krantz

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    2. The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pennsylvania
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  • How to Cite this Article: Conlin LK, Kaur M, Izumi K, Campbell L, Wilkens A, Clark D, Deardorff MA, Zackai EH, Pallister P, Hakonarson H, Spinner NB, Krantz ID. 2012. Utility of SNP arrays in detecting, quantifying, and determining meiotic origin of tetrasomy 12p in blood from individuals with Pallister–Killian syndrome. Am J Med Genet Part A 158A: 3046–3053.

Abstract

Identification of the isochromosome 12p (i(12p)) associated with Pallister–Killian syndrome is complicated by the low frequency of this supernumerary chromosome in PHA stimulated peripheral blood lymphocytes, and frequently requires cytogenetic analysis of fibroblast cells. Recently, it has been shown that array CGH techniques are able to detect tetrasomy 12p in peripheral blood, even when not identified by traditional cytogenetic techniques. We studied 15 patients with a previous cytogenetic and clinical diagnosis of Pallister–Killian syndrome using genome-wide SNP arrays to investigate the ability of this platform to identify the i(12p) in blood and tissue. Array analysis verified tetrasomy 12p in all samples from fibroblasts, but was only able to detect it in 46% of blood samples. The genotyping information available from the SNP arrays allowed for the detection of as low as 5% mosaicism, as well as suggesting a Meiosis II origin for the isochromosome in the majority of patients. Analysis of the percentage of abnormal cells with patient age at time of study suggests that the frequency of the i(12p) decreased with age in blood, but not in fibroblasts. These highlight the power of SNP arrays in detecting and characterizing the isochromosome 12p in Pallister–Killian syndrome as well as underscoring the important utility of traditional cytogenetic techniques. © 2012 Wiley Periodicals, Inc.

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