title: Variable presentation of primary immune deficiency: two cases with CD3 gamma deficiency presenting with only autoimmunity.
abstract: BACKGROUND
  CD3 chain expression defects including CD3 gamma, epsilon, delta, and zeta chain subunits, are autosomal recessive inherited severe combined immunodeficiencies (SCID). The phenotype is usually T-B+NK+ SCID with lymphopenia where the clinical findings may be mild (CD3γ) or severe (CD3δ, ε, ζ) owing to the underlying molecular defect. There is limited information about the disease in literature.
  
  
  METHODS
  Here, we present two siblings from non-consanguineous family with autoimmunity including Evans syndrome, autoimmune hepatitis, nephrotic syndrome, and Hashimoto's thyroiditis and with no previous history of infections. To define the molecular basis of the disease, we performed linkage analysis around the CD3 receptor cluster and found consistent linkage to this region.
  
  
  RESULTS
  The patient one displayed low TCRαβ expression, low IgG, low IgA, low IgM, low CD3, low CD4, low CD8. The patient two also displayed low TCRαβ expression and low anti-HBs titer. We went onto identify a homozygous splicing mutation (IVS2-1G>C) in the two affected individuals in the CD3γ gene.
  
  
  CONCLUSIONS
  To date, only four cases have been reported with CD3γ deficiency. Occasionally, the patients present with only autoimmunity including autoimmune hemolytic anemia, vitiligo, Hashimoto's thyroiditis, and autoimmune enteropathy. However, Evans syndrome, autoimmune hepatitis, and nephrotic syndrome have not been reported in previous cases. We believe that our cases will contribute to the literature.
authors.affiliation: Department of Pediatric Hematology, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey. drhuseyintokgoz@hotmail.com
authors.forename: Huseyin
authors.initials: H
authors.lastname: Tokgoz
authors.forename: Umran
authors.initials: U
authors.lastname: Caliskan
authors.forename: Sevgi
authors.initials: S
authors.lastname: Keles
authors.forename: Ismail
authors.initials: I
authors.lastname: Reisli
authors.forename: Isabel Sánchez
authors.initials: IS
authors.lastname: Guiu
authors.forename: Neil V
authors.initials: NV
authors.lastname: Morgan
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood; D015551:Autoimmunity; D017252:CD3 Complex / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D010375:Pedigree; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D035781:Siblings; D055815:Young Adult
chemical_list: D000906:Antibodies; D017252:CD3 Complex; C452842:CD3 antigen, gamma chain; D016693:Receptors, Antigen, T-Cell, alpha-beta