A hypomorphic recombination-activating gene 1 (RAG1) mutation resulting in a phenotype resembling common variable immunodeficiency

作者：Abolhassani Hassan; Wang Ning; Aghamohammadi Asghar; Rezaei Nima; Lee Yu Nee; Frugoni Francesco; Notarangelo Luigi D; Pan Hammarstrom Qiang; Hammarstrom Lennart^*

来源：Journal of Allergy and Clinical Immunology, 2014, 134(6): 1375-1380.

DOI：10.1016/j.jaci.2014.04.042

• Common variable immunodeficiency
• granulomatous lesion
• recombination activation genes
• differential diagnosis
• mismanagement

Background: Recombination-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. %26lt;br%26gt;Objective: We sought to assess the genetic background of patients with common variable immunodeficiency (CVID). %26lt;br%26gt;Methods: A 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. %26lt;br%26gt;Results: The 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%26gt;A, p.C358Y) with a residual functional capacity of 48% of wild-type protein. %26lt;br%26gt;Conclusion: Our finding broadens the range of disorders associated with RAG1 mutations and might have important therapeutic implications.

• 出版日期2014-12