Clinical, immunologic, and genetic characteristics of RAG mutations in 15 Chinese patients with SCID and Omenn syndrome

Immunol Res. 2016 Apr;64(2):497-507. doi: 10.1007/s12026-015-8723-4.

Abstract

Mutations in Recombination Activating Genes (RAG1 and RAG2) are common genetic causes of severe combined immunodeficiency (SCID) and Omenn syndrome (OS). The clinical, immunologic, and genetic characteristics of RAG mutations in Chinese patients with SCID or OS have not been studied in detail. In this research, 22 RAG mutations were identified in 15 Chinese patients, including 10 novel mutations in RAG1 (R108X, M630T, E510X, S666P, E669K, C730Y, A857V, K847E, L922PfsX7, and L1025FfsX39) and 4 in RAG2 (R73C, I427GfsX12, P432L, and 311insL). L1025FfsX39 is a potential RAG1 hot-spot mutation in the Chinese population. The distribution of RAG1 mutations rather than mutation type seemed to differ between SCID and OS patients. The thymic output of T lymphocytes, TCR rearrangement, and T cell proliferation were severely impaired in RAG mutant patients. These findings will contribute to the early diagnosis and treatment of SCID and OS to a certain extent.

Keywords: Mutation; Omenn syndrome; Recombination Activating Gene 1; Recombination Activating Gene 2; Severe combined immunodeficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Asian People / genetics
  • China
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Female
  • Genotype
  • Homeodomain Proteins / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Lymphocyte Activation
  • Lymphocyte Count
  • Male
  • Mutation*
  • Receptors, Antigen, T-Cell / genetics
  • Severe Combined Immunodeficiency / diagnosis
  • Severe Combined Immunodeficiency / genetics*
  • Severe Combined Immunodeficiency / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Receptors, Antigen, T-Cell
  • V(D)J recombination activating protein 2
  • RAG-1 protein