Journal of Clinical Immunology

, Volume 31, Issue 5, pp 773–777

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


DOI: 10.1007/s10875-011-9561-3

Cite this article as:
Buchbinder, D., Nadeau, K. & Nugent, D. J Clin Immunol (2011) 31: 773. doi:10.1007/s10875-011-9561-3


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.


Primary immunodeficiency epigenetic methylation thrombocytopenia 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Division of Pediatric Hematology, Children’s Hospital Orange CountyUniversity of California at IrvineOrangeUSA
  2. 2.Division of Immunology and Allergy, Lucile Packard Children’s HospitalStanford UniversityPalo AltoUSA
  3. 3.Division of Hematology, Children’s Hospital Orange CountyUniversity of California at IrvineOrangeUSA

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