The phenotype of persons having mosaicism for trisomy 21/Down syndrome reflects the percentage of trisomic cells present in different tissues

Authors

  • Paulie Papavassiliou,

    1. Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia
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  • Timothy P. York,

    1. Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia
    2. Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia
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  • Nurcan Gursoy,

    1. Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia
    2. Department of Neurology, State University of New York at Stony Brook, Stony Brook, New York
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  • Gloria Hill,

    1. Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia
    2. Virginia Department of Forensic Science, Norfolk, Virginia
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  • Lauren Vanner Nicely,

    1. Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia
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  • Usha Sundaram,

    1. Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia
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  • Allison McClain,

    1. Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia
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  • Steven H. Aggen,

    1. Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia
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  • Lindon Eaves,

    1. Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia
    2. Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia
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  • Brien Riley,

    1. Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia
    2. Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia
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  • Colleen Jackson-Cook

    Corresponding author
    1. Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia
    2. The Department of Pathology, Virginia Commonwealth University, Richmond, Virginia
    • Department of Pathology, Virginia Commonwealth University, P.O. Box 980662, Richmond, VA 23298-0662.
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  • How to Cite this Article: Papavassiliou P, York TP, Gursoy N, Hill G, Nicely LV, Sundaram U, McClain A, Aggen SH, Eaves L, Riley B, Jackson-Cook C. 2009. The phenotype of persons having mosaicism for trisomy 21/Down syndrome reflects the percentage of trisomic cells present in different tissues. Am J Med Genet Part A 149A:573–583.

Abstract

Little is known about the pathogenesis of the phenotype in individuals with trisomy 21 mosaicism and Down syndrome. The primary goal of this study was to identify factors contributing to the observed phenotypic variation by evaluating 107 individuals having trisomy 21 mosaicism. To investigate a potential “threshold” effect due to trisomic imbalance, lymphocyte and buccal mucosa nuclei were scored using FISH. Overall, buccal cells showed a significantly higher frequency of trisomy than lymphocytes (P < 0.0001). Using latent class analysis, two phenotypic classes were identified based on the clinical findings of the propositi. Patients from class 1 had significantly fewer traits and a lower percentage of trisomic cells (mean of 37.3% lymphocytes; 34.5% buccal mucosa cells) when compared to those stratified into class 2 (54.0% lymphocytes; 53.4% buccal mucosa cells). Tissue-specific influences were also detected, with buccal mucosa trisomy levels being significantly correlated with IQ (P = 0.0094; both ectodermal derivatives), while congenital heart defects were significantly correlated with lymphocytes (P = 0.0286; both mesodermal embryonic derivatives). In conclusion, allowing for the distinction of two groups, we observed variation in phenotype, associated with the percentage of trisomic cells. We also observed tissue-specific effects on phenotype. The results of this study should enable geneticists and other health care professionals to provide information regarding optimal diagnostic approaches and anticipated clinical outcomes. © 2009 Wiley-Liss, Inc.

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