title: Genotype, phenotype, and outcomes of nine patients with T-B+NK+ SCID.
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.
authors: Division of Immunology and Allergy, Department of Pediatrics, Stanford University School of Medicine and Lucile Packard Children's Hospital at Stanford, Palo Alto, CA, USA.
authors: Grace P
authors: GP
authors: Yu
authors: Kari C
authors: KC
authors: Nadeau
authors: David R
authors: DR
authors: Berk
authors: Geneviève
authors: G
authors: de Saint Basile
authors: Nathalie
authors: N
authors: Lambert
authors: Perrine
authors: P
authors: Knapnougel
authors: Joseph
authors: J
authors: Roberts
authors: Kristina
authors: K
authors: Kavanau
authors: Elizabeth
authors: E
authors: Dunn
authors: E Richard
authors: ER
authors: Stiehm
authors: David B
authors: DB
authors: Lewis
authors: Dale T
authors: DT
authors: Umetsu
authors: Jennifer M
authors: JM
authors: Puck
authors: Morton J
authors: MJ
authors: Cowan
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology*; D017252:CD3 Complex / Q000096:biosynthesis* / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D005838:Genotype; D006680:HLA Antigens / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015851:Interleukin-7 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009154:Mutation; D010641:Phenotype; D016511:Severe Combined Immunodeficiency / Q000097:blood* / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology*; D016896:Treatment Outcome
chemical_list: D017252:CD3 Complex; C472562:CD3delta antigen; D006680:HLA Antigens; D015851:Interleukin-7