Genotype, phenotype, and outcomes of nine patients with T-B+NK+ SCID

Pediatr Transplant. 2011 Nov;15(7):733-41. doi: 10.1111/j.1399-3046.2011.01563.x. Epub 2011 Aug 23.

Abstract

There are few reports of clinical presentation, genotype, and HCT outcomes for patients with T-B+NK+ SCID. Between 1981 and 2007, eight of 84 patients with SCID who received and/or were followed after HCT at UCSF had the T-B+NK+ phenotype. One additional patient with T-B+NK+ SCID was identified as the sibling of a patient treated at UCSF. Chart reviews were performed. Molecular analyses of IL7R, IL2RG, JAK3, and the genes encoding the CD3 T-cell receptor components δ (CD3D), ε (CD3E), and ζ (CD3Z) were carried out. IL7R mutations were documented in four patients and CD3D mutations in two others. Three patients had no defects found. Only two of nine patients had an HLA-matched related HCT donor. Both survived, and neither developed GVHD. Five of seven recipients of haploidentical grafts survived. Although the majority of reported cases of T-B+NK+ SCID are caused by defects in IL7R, CD3 complex defects were also found in this series and should be considered when evaluating patients with T-B+NK+ SCID. Additional genes, mutations in which account for T-B+NK+ SCID, remain to be found. Better approaches to early diagnosis and HCT treatment are needed for patients lacking an HLA-matched related donor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / cytology*
  • CD3 Complex / biosynthesis*
  • CD3 Complex / genetics
  • DNA Mutational Analysis
  • Female
  • Fibroblasts / metabolism
  • Flow Cytometry / methods
  • Genotype
  • HLA Antigens / metabolism
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Infant
  • Infant, Newborn
  • Interleukin-7 / genetics
  • Interleukin-7 / metabolism*
  • Male
  • Mutation
  • Phenotype
  • Severe Combined Immunodeficiency / blood*
  • Severe Combined Immunodeficiency / genetics
  • T-Lymphocytes / cytology*
  • Treatment Outcome

Substances

  • CD3 Complex
  • CD3delta antigen
  • HLA Antigens
  • Interleukin-7