Here, we report the biochemical and functional characterization of a nonsense mutation in exon 8 (p.R328X) of IL2RG in 2 siblings: a 4-year-old boy with lethal Epstein Barr virus-related lymphoma and his asymptomatic 8-month-old brother with a T<sup>low</sup> B<sup>+</sup> NK<sup>+</sup> immunophenotype, dysgammaglobulinemia, abnormal lymphocyte proliferation, and reduced levels of T cell receptor excision circles.