Multiple independent second-site mutations in two siblings with somatic mosaicism for Wiskott-Aldrich syndrome

K. Boztug, M. Germeshausen, I. Avedillo Díez, V. Gulacsy, J. Diestelhorst, M. Ballmaier, K. Welte, L. Maródi, L. I. Chernyshova, Christoph Klein

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Abstract

Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disorder associated with microthrombocytopenia, eczema, autoimmunity and predisposition to malignant lymphoma. Although rare, few cases of somatic mosaicism have been published in WAS patients to date. We here report on two Ukrainian siblings who were referred to us at the age of 3 and 4years, respectively. Both patients suffered from severe WAS caused by a nonsense mutation in exon 1 of the WAS gene. In both siblings, flow cytometric analysis revealed the presence of Wiskott-Aldrich syndrome protein (WASp)-positive and WASp-negative cell populations among T and B lymphocytes as well as natural killer (NK) cells. In contrast to previously described cases of revertant mosaicism in WAS, molecular analyses in both children showed that the WASp-positive T cells, B cells, and NK cells carried multiple different second-site mutations, resulting in different missense mutations. To our knowledge, this is the first report describing somatic mosaicism in WAS patients caused by several independent second-site mutations in the WAS gene.

Original languageEnglish
Pages (from-to)68-74
Number of pages7
JournalClinical Genetics
Volume74
Issue number1
DOIs
Publication statusPublished - Jul 1 2008

Keywords

  • Aldrich syndrome
  • Gene therapy
  • Second-site mutation
  • Somatic mosaicism
  • Somatic reversion
  • Wiskott

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Boztug, K., Germeshausen, M., Avedillo Díez, I., Gulacsy, V., Diestelhorst, J., Ballmaier, M., Welte, K., Maródi, L., Chernyshova, L. I., & Klein, C. (2008). Multiple independent second-site mutations in two siblings with somatic mosaicism for Wiskott-Aldrich syndrome. Clinical Genetics, 74(1), 68-74. https://doi.org/10.1111/j.1399-0004.2008.01019.x