Combined immunodeficiency with EBV positive B cell lymphoma and epidermodysplasia verruciformis due to a novel homozygous mutation in RASGRP1

Clin Immunol. 2017 Oct:183:142-144. doi: 10.1016/j.clim.2017.08.007. Epub 2017 Aug 16.

Abstract

RASGRP1 is a guanine-nucleotide-exchange factor essential for MAP-kinase mediated signaling in lymphocytes. We report the second case of RASGRP1 deficiency in a patient with a homozygous nonsense mutation in the catalytic domain of the protein. The patient had epidermodysplasia verruciformis, suggesting a clinically important intrinsic T cell function defect. Like the previously described patient, our proband also presented with CD4+ T cell lymphopenia, impaired T cell proliferation to mitogens and antigens, reduced NK cell function, and EBV-associated lymphoma. The severity of the disease and the development of EBV lymphoma in both patients suggest that hematopoietic stem cell transplantation should be performed rapidly in patients with RASGRP1 deficiency.

Keywords: Epidermodysplasia verruciformis; Epstein Barr Virus; Lymphoma; RASGRP1 deficiency.

Publication types

  • Case Reports
  • Letter
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes
  • Child
  • Codon, Nonsense
  • Consanguinity
  • DNA-Binding Proteins / genetics*
  • Epidermodysplasia Verruciformis / complications
  • Epidermodysplasia Verruciformis / genetics*
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / genetics*
  • Fatal Outcome
  • Female
  • Guanine Nucleotide Exchange Factors / genetics*
  • Homozygote
  • Humans
  • Immunologic Deficiency Syndromes / genetics*
  • Lymphoma, Large B-Cell, Diffuse / complications
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / virology
  • Lymphopenia / complications
  • Lymphopenia / genetics*
  • Severity of Illness Index

Substances

  • Codon, Nonsense
  • DNA-Binding Proteins
  • Guanine Nucleotide Exchange Factors
  • RASGRP1 protein, human