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Monozygotic Twin Pair Showing Discordant Phenotype for X-linked Thrombocytopenia and Wiskott–Aldrich Syndrome: a Role for Epigenetics?

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Abstract

Despite our increasing characterization of the molecular basis for many primary immunodeficiency states, significant heterogeneity in clinical and immunological phenotype exists. Epigenetic alterations have been implicated in the pathogenesis of immune dysregulation and may provide a unique paradigm to help us understand the phenotypic heterogeneity in primary immunodeficiency. The occurrence of X-linked thrombocytopenia (XLT) and Wiskott–Aldrich syndrome (WAS) in monozygotic twins is a rare occurrence which allows for the exploration of epigenetic alterations and associated phenotypic heterogeneity. We describe a pair of monozygotic twin brothers with a missense mutation in the WAS gene consistent with reduced expression of the WAS protein, a XLT phenotype, and a good prognosis. Despite this genotype and anticipated mild phenotype in both twins, a discordant phenotype has evolved in which one twin demonstrates asymptomatic thrombocytopenia and the other symptomatic thrombocytopenia, infectious complications, and autoimmunity. Characterization of the potential epigenetic contribution to the spectrum of XLT and WAS is described and the implications of these findings are discussed.

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Acknowledgments

We would also like to acknowledge the assistance of David Lewis, MD, Michael Jeng, MD, Kenneth Weinberg, MD, and Stephen Mao, PhD for their assistance in the preparation of this manuscript.

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Authors and Affiliations

  1. Division of Pediatric Hematology, Children’s Hospital Orange County, University of California at Irvine, Orange, CA, USA

    David Buchbinder & Diane Nugent

  2. Division of Immunology and Allergy, Lucile Packard Children’s Hospital, Stanford University, Palo Alto, CA, USA

    Kari Nadeau

  3. Division of Hematology, Children’s Hospital Orange County, University of California at Irvine, 455 S. Main Street, Orange, CA, 92868, USA

    David Buchbinder

Authors
  1. David Buchbinder
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  2. Kari Nadeau
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  3. Diane Nugent
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Correspondence to David Buchbinder.

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David Buchbinder and Kari Nadeau are co-first authors.

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Buchbinder, D., Nadeau, K. & Nugent, D. Monozygotic Twin Pair Showing Discordant Phenotype for X-linked Thrombocytopenia and Wiskott–Aldrich Syndrome: a Role for Epigenetics?. J Clin Immunol 31, 773–777 (2011). https://doi.org/10.1007/s10875-011-9561-3

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  • DOI: https://doi.org/10.1007/s10875-011-9561-3

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