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RAG1 Deficiency May Present Clinically as Selective IgA Deficiency
- Source :
- Journal of Clinical Immunology. 35:280-288
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Recombination-activating gene (RAG) 1 and 2 deficiency is seen in patients with severe combined immunodeficiency (SCID) and Omenn syndrome. However, the spectrum of the disease has recently expanded to include a milder phenotype.We analyzed a 4-year-old boy who was initially given the diagnosis of selective immunoglobulin A deficiency (SIgAD) based on immunoglobulin serum levels without any opportunistic infections, rashes, hepatosplenomegaly, autoimmunity or granulomas. The patient was found to be infected with varicella zoster; however, the clinical course was not serious. He produced antiviral antibodies.We performed lymphocyte phenotyping, quantification of T cell receptor excision circles (TRECs) and kappa deleting recombination excision circles (KRECs), an analysis of target sequences of RAG1 and 2, a whole-genome SNP array, an in vitro V(D)J recombination assay, a spectratype analysis of the CDR3 region and a flow cytometric analysis of the bone marrow.Lymphocyte phenotyping demonstrated that the ratio of CD4+ to CD8+ T cells was inverted and the majority of CD4+T cells expressed CD45RO antigens in addition to the almost complete lack of B cells. Furthermore, both TRECs and KRECs were absent. Targeted DNA sequencing and SNP array revealed that the patient carried a deletion of RAG1 and RAG2 genes on the paternally-derived chromosome 11, and two maternally-derived novel RAG1 missense mutations (E455K, R764H). In vitro analysis of recombination activity showed that both RAG1 mutant proteins had low, but residual function.The current case further expands the phenotypic spectrum of mild presentations of RAG deficiency, and suggests that TRECs and KRECs are useful markers for detecting hidden severe, as well as mild, cases.
- Subjects :
- Homeodomain Proteins
Male
Severe combined immunodeficiency
medicine.medical_specialty
business.industry
Immunology
IgA Deficiency
Receptors, Antigen, T-Cell
Disease
Selective IgA deficiency
medicine.disease
Polymorphism, Single Nucleotide
Phenotype
V(D)J Recombination
Recombination-activating gene
Omenn syndrome
Medical microbiology
Child, Preschool
Mutation
Primary immunodeficiency
medicine
Humans
Immunology and Allergy
business
Subjects
Details
- ISSN :
- 15732592 and 02719142
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Immunology
- Accession number :
- edsair.doi.dedup.....02b27411e33fb23e73bcafbbce8a3380