Distinct types of severe combined immunodeficiency (SCID) (a growing list; see Ochs et al, 199910 ; Chapel et al, 20039 ).
| Defects in Cytokine Receptors and Cytokine Signaling (B cells generally present but nonfunctional) |
| X-linked SCID, due to defects in the γc chain found in receptors for interleukin (IL)-2, -4, -7, -9, -15, and -21 |
| JAK3 deficiency, due to defects in the Janus signaling kinase that interacts with the intracellular portion of the common gamma chain |
| IL-7 receptor alpha chain deficiency, due to defects in the receptor for IL-7, critical for lymphoid cell development and differentiation |
| CD45 deficiency, due to defects in a transmembrane tyrosine phosphatase |
| Defects in Recombination of the Antigen Receptor Genes of B cells and T cells (T and B cells absent) |
| Recombinase activating gene 1 (RAG1) deficiency |
| Recombinase activating gene 2 (RAG2) deficiency |
| Artemis deficiency (another component of the recombinase system) |
| Defects in purine pathway enzymes that result in buildup of metabolites toxic to lymphocytes |
| Adenosine deaminase (ADA) deficiency |
| Purine nucleoside phosphorylase (PNP) deficiency |
| Other lymphocyte specific gene disorders (may have partial preservation of some lymphocyte lineages/function) |
| CD3 deficiency |
| ZAP70 deficiency |
| MHC Class II deficiency due to diverse gene defects in transcription factors for the Class II molecules |
| MHC Class I deficiency due to defects in TAP1/TAP2, transporters involved in Class I expression |
| SCID phenotype as a component of syndromes (severity of disease may be variable) |
| Cartilage hair hypoplasia, due to defects in RMRP, an RNA component of a ribonucleoprotein RNAse |
| Severe DiGeorge syndrome, in 90% of cases associated with heterozygous deletion of chromosome 22q11 |
| SCID with alopecia and nail dystrophy (orthologous to nude mouse) due to defects in winged helix nude (WHN) transcription factor |
| SCID with multiple bowel atresias |
| Reticular dysgenesis, a stem cell defect with impaired maturation of multiple bone marrow lineages |
| Defects in Cytokine Receptors and Cytokine Signaling (B cells generally present but nonfunctional) |
| X-linked SCID, due to defects in the γc chain found in receptors for interleukin (IL)-2, -4, -7, -9, -15, and -21 |
| JAK3 deficiency, due to defects in the Janus signaling kinase that interacts with the intracellular portion of the common gamma chain |
| IL-7 receptor alpha chain deficiency, due to defects in the receptor for IL-7, critical for lymphoid cell development and differentiation |
| CD45 deficiency, due to defects in a transmembrane tyrosine phosphatase |
| Defects in Recombination of the Antigen Receptor Genes of B cells and T cells (T and B cells absent) |
| Recombinase activating gene 1 (RAG1) deficiency |
| Recombinase activating gene 2 (RAG2) deficiency |
| Artemis deficiency (another component of the recombinase system) |
| Defects in purine pathway enzymes that result in buildup of metabolites toxic to lymphocytes |
| Adenosine deaminase (ADA) deficiency |
| Purine nucleoside phosphorylase (PNP) deficiency |
| Other lymphocyte specific gene disorders (may have partial preservation of some lymphocyte lineages/function) |
| CD3 deficiency |
| ZAP70 deficiency |
| MHC Class II deficiency due to diverse gene defects in transcription factors for the Class II molecules |
| MHC Class I deficiency due to defects in TAP1/TAP2, transporters involved in Class I expression |
| SCID phenotype as a component of syndromes (severity of disease may be variable) |
| Cartilage hair hypoplasia, due to defects in RMRP, an RNA component of a ribonucleoprotein RNAse |
| Severe DiGeorge syndrome, in 90% of cases associated with heterozygous deletion of chromosome 22q11 |
| SCID with alopecia and nail dystrophy (orthologous to nude mouse) due to defects in winged helix nude (WHN) transcription factor |
| SCID with multiple bowel atresias |
| Reticular dysgenesis, a stem cell defect with impaired maturation of multiple bone marrow lineages |