Abstract
Mutations in RAG1 gene may result in different types of severe combined immunodeficiencies. In this study, we compare clinical symptoms and laboratory findings in four children with identical mutation in RAG1 gene. All of analyzed patients presented symptoms of severe combined immunodeficiencies associated or not with Omenn syndrome (OS) features. In our patients two different types of variants in RAG1 gene were detected. The first of the mutation was the deletion of AA dinucleotide at position c.256_257 (p.Lys86ValfsTer33), the second gene variant was substitution c.2867T>C (p.Ile956Thr). In Patient 1 we detected that compound heterozygous mutations involved both of the mentioned variants. Whereas, in Patients 2, 3 and 4, we confirmed the presence of the dinucleotide deletion but in a homozygous state. In all described patients, sequence analysis of RAG2 gene did not reveal any nucleotide changes. Our data show that mutation c.256_257delAA in RAG1 gene seems to occur quite frequently in the polish patients with severe combined immunodeficiency and may result in classical OS as well as in severe combined immunodeficiency without clinical and laboratory features of OS when occurred in homozygous state. The same mutation but in heterozygous state, in combination with other mutation in RAG1 gene, may result in incomplete OS.
Highlights
The recombination-activating gene (RAG) 1 and RAG2 proteins, encoded by two genes RAG1 and RAG2, respectively, on chromosome 11p23, are lymphoid-specific components of the complex of enzymes termed the V(D)J recombinases
Sanger sequencing of RAG1 gene performed in Patients 2, 3 and 4 confirmed the presence of the first of the mentioned gene variants, dinucleotide deletion at position c.256_257 but in a homozygous state
We described patients with severe combined immunodeficiency (SCID) in whom the same mutations (c.256_257delAA) in RAG1 gene were detected, both in the heterozygous (Patient 1) or homozygous state (Patient 2, 3 and 4)
Summary
The recombination-activating gene (RAG) 1 and RAG2 proteins, encoded by two genes RAG1 and RAG2, respectively, on chromosome 11p23, are lymphoid-specific components of the complex of enzymes termed the V(D)J recombinases. They play a pivotal role in the process of rearrangement of the variable (V), diversity (D) and joining (J) segments during the development of the immunoglobulin and T-cell receptors. Hypomorphic mutations associated with residual RAGs activity can result in different immunologic phenotypes. These include: Omenn syndrome (OS), characterized by erythroderma, lymphadenopathy, eosinophilia, S178
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