Abstract
The V(D)J recombination, which leads to the somatic rearrangement of variable, diversity, and joining segments, is the mechanism accountable for the diversity of T cell receptor- and Ig-encoding genes. The products of the RAG1 and RAG2 genes are the lymphoid-specific factors responsible for the initiation of the V(D)J recombination through the generation of a DNA double strand break. RAG1 or RAG2 gene inactivation in the mouse leads to abortion of the V(D)J rearrangement process, early block in both T and B cell maturation, and, ultimately, to severe combined immune deficiency (SCID). A human SCID condition is also characterized by an absence of mature T and B lymphocytes and is associated with mutations in either RAG1- or RAG2-encoding genes. Based on the predicted beta-propeller three-dimensional structure model for RAG2, we found that six out of the seven mutations described to date in T-B-SCID patients are clustered on one side of the propeller, in regions exposed to solvent. This finding reinforces the biological significance of this predicted model and suggests that RAG1 interacts with RAG2 on one of the side of the scaffold formed by the beta-propeller.
Highlights
Immunoglobulin and T-cell receptor genes are composed of variable (V),1 diversity (D), and joining (J) segments, which undergo somatic rearrangements prior to their expression
Three Novel RAG2 Mutations in T-B- severe combined immune deficiency (SCID) Patients—Two classes of T-B-SCID patients have been described that can be distinguished based on the affected step of the V(D)J recombination process
Patient 41 carried two missense mutations in the RAG2 gene: an A1316G transversion causing an R39G amino acid substitution and a G1887A transversion leading to an R229E substitution
Summary
Immunoglobulin and T-cell receptor genes are composed of variable (V),1 diversity (D), and joining (J) segments, which undergo somatic rearrangements prior to their expression. Some patients have been found to carry mutations in either the RAG1- or the RAG2-encoding genes, which compromise the early step of the V(D)J recombination [8].
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