Hassan Abolhassani1, Ning Wang2, Asghar Aghamohammadi3, Nima Rezaei3, Yu Nee Lee4, Francesco Frugoni4, Luigi D Notarangelo4, Qiang Pan-Hammarström2, Lennart Hammarström5. 1. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran. 2. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden. 3. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran. 4. Division of Immunology and the Manton Center for Orphan Disease Research, Boston Children's Hospital, and the Harvard Stem Cell Institute, Harvard Medical School, Boston, Mass. 5. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden. Electronic address: lennart.hammarstrom@ki.se.
Abstract
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. OBJECTIVE: We sought to assess the genetic background of patients with common variable immunodeficiency (CVID). 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. 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>A, p.C358Y) with a residual functional capacity of 48% of wild-type protein. CONCLUSION: Our finding broadens the range of disorders associated with RAG1 mutations and might have important therapeutic implications.
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. OBJECTIVE: We sought to assess the genetic background of patients with common variable immunodeficiency (CVID). 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. 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>A, p.C358Y) with a residual functional capacity of 48% of wild-type protein. CONCLUSION: Our finding broadens the range of disorders associated with RAG1 mutations and might have important therapeutic implications.
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