Immune deficiencies, infection, and systemic immune disordersA hypomorphic recombination-activating gene 1 (RAG1) mutation resulting in a phenotype resembling common variable immunodeficiency

BackgroundRecombination-activating gene 1 (RAG1) deficiency presents with a varied spectrum of combined immunodeficiency, ranging from a T−B−NK+ type of disease to a T+B+NK+ phenotype.ObjectiveWe sought to assess the genetic background of patients with common variable immunodeficiency (CVID).MethodsA patient given a diagnosis of CVID, who was born to a consanguineous family and thus would be expected to show an autosomal recessive inheritance, was subjected to clinical evaluation, immunologic assays, homozygosity gene mapping, exome sequencing, Sanger sequencing, and functional analysis.ResultsThe 14-year-old patient, who had liver granuloma, extranodal marginal zone B-cell lymphoma, and autoimmune neutropenia, presented with a clinical picture resembling CVID. Genetic analysis of this patient showed a homozygous hypomorphic RAG1 mutation (c.1073 G>A, p.C358Y) with a residual functional capacity of 48% of wild-type protein.ConclusionOur finding broadens the range of disorders associated with RAG1 mutations and might have important therapeutic implications.