Molecular diagnosis of severe combined immunodeficiency--identification of IL2RG, JAK3, IL7R, DCLRE1C, RAG1, and RAG2 mutations in a cohort of Chinese and Southeast Asian children

J Clin Immunol. 2011 Apr;31(2):281-96. doi: 10.1007/s10875-010-9489-z. Epub 2010 Dec 24.

Abstract

Severe combined immunodeficiencies (SCID) are a group of rare inherited disorders with profound defects in T cell and B cell immunity. From 2005 to 2010, our unit performed testing for IL2RG, JAK3, IL7R, RAG1, RAG2, DCLRE1C, LIG4, AK2, and ZAP70 mutations in 42 Chinese and Southeast Asian infants with SCID adopting a candidate gene approach, based on patient's gender, immune phenotype, and inheritance pattern. Mutations were identified in 26 patients, including IL2RG (n = 19), IL7R (n = 2), JAK3 (n = 2), RAG1 (n = 1), RAG2 (n = 1), and DCLRE1C (n = 1). Among 12 patients who underwent hematopoietic stem cell transplantation, eight patients survived. Complications and morbidities during transplant period were significant, especially disseminated bacillus Calmette-Guérin disease which was often difficult to control. This is the first cohort study on SCID in the Chinese and Southeast Asian population, based on a multi-centered collaborative research network. The foremost issue is service provision for early detection, diagnosis, management, and definitive treatment for patients with SCID. National management guidelines for SCID should be established, and research into an efficient platform for genetic diagnosis is needed.

MeSH terms

  • Agammaglobulinemia / etiology
  • Agammaglobulinemia / immunology
  • Asian Continental Ancestry Group / genetics
  • Child, Preschool
  • Cohort Studies
  • DNA-Binding Proteins / genetics
  • Endonucleases
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Homeodomain Proteins / genetics
  • Humans
  • Infant
  • Infant, Newborn
  • Infections / etiology
  • Interleukin Receptor Common gamma Subunit / genetics
  • Janus Kinase 3 / genetics
  • Leukopenia / etiology
  • Leukopenia / immunology
  • Male
  • Mutation / genetics*
  • Nuclear Proteins / genetics
  • Receptors, Interleukin-7 / genetics
  • Severe Combined Immunodeficiency / complications
  • Severe Combined Immunodeficiency / diagnosis*
  • Severe Combined Immunodeficiency / genetics*
  • Severe Combined Immunodeficiency / therapy
  • Treatment Outcome

Substances

  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Interleukin Receptor Common gamma Subunit
  • Nuclear Proteins
  • RAG2 protein, human
  • Receptors, Interleukin-7
  • RAG-1 protein
  • Janus Kinase 3
  • DCLRE1C protein, human
  • Endonucleases