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Severe XLP Phenotype Caused by a Novel Intronic Mutation in the SH2D1A Gene

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Abstract

We describe here a novel c.137 + 5G > A intronic mutation in the SH2D1A gene of the signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) in association with Epstein-Barr virus (EBV)-induced fatal infectious mononucleosis (FIM) in an 8-year-old male patient and his 3-year-old step brother. The mother and the maternal grandmother of the boys are healthy and heterozygous for this sequence variant. Genetic sequencing of blood-cell-derived cDNA in the younger patient revealed a 22 bp deletion in the SH2D1A cDNA. Immunoblot and flow cytometry analysis performed in this younger patient showed the lack of SAP protein expression in peripheral blood lymphocytes. These data suggest that the novel c.137 + 5G > A mutation results in loss of function of SAP protein and leads to typical X-linked lymphoproliferative disease phenotype. We propose that intron 1 and the c.137 + 5G may be the most frequent intronic hot spot for SH2D1A splicing mutation.

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Acknowledgments

We thank J. Sümegi, R. Marsch and G. Kriván for help. This work was supported by the TÁMOP 4.2.2.A-11/1/KONV-2012-0023 “VÉD-ELEM” project grant to LM.

Conflicts of interest

The authors have no competing financial interests to declare.

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Authors and Affiliations

  1. Department of Infectious Diseases and Pediatric Immunology, Faculty of Medicine, University of Debrecen, Nagyerdei Krt. 98, 4012, Debrecen, Hungary

    B. Tóth, B. Soltész, G. Csorba, L. Maródi & M. Erdős

  2. Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

    E. Gyimesi

  3. Institute of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

    Á. Veres & Á. Lányi

  4. 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary

    G. Kovács

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  1. B. Tóth
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  2. B. Soltész
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  3. E. Gyimesi
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  4. G. Csorba
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  5. Á. Veres
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  6. Á. Lányi
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  7. G. Kovács
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  8. L. Maródi
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  9. M. Erdős
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Correspondence to M. Erdős.

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Shared last authorship L Maródi and M. Erdős

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Tóth, B., Soltész, B., Gyimesi, E. et al. Severe XLP Phenotype Caused by a Novel Intronic Mutation in the SH2D1A Gene. J Clin Immunol 35, 26–31 (2015). https://doi.org/10.1007/s10875-014-0117-1

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  • DOI: https://doi.org/10.1007/s10875-014-0117-1

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