Autosomal recessive immunodeficiencies
| Disorder (year of definition of molecular basis) | Chromosomal localisation | Gene | Function/defect | Diagnostic test(s) |
|---|---|---|---|---|
| FACS, fluorescence activated cell sorting analysis; IL, interleukin; MHC, major histocompatibility complex; NK, natural killer cell; SCID, severe combined immune deficiency. | ||||
| I. Severe combined immunodeficiency | ||||
| Adenosine deaminase (ADA) deficiency (1983) | 20q12-13 | Adenosine deaminase | Enzyme in purine salvage pathway; accumulation of toxic metabolites | Red cell ADA levels and metabolites |
| Mutation analysis | ||||
| Purine nucleoside phosphorylase (PNP) deficiency (1987) | 14q11 | Purine nucleoside phosphorylase | Enzyme in purine salvage pathway; accumulation of toxic metabolites | Red cell PNP levels and metabolites |
| Mutation analysis | ||||
| Recombinase activating gene (RAG 1 and 2) deficiency (1996) | 11p13 | RAG1 and RAG2 | Defective DNA recombination affecting immunoglobulin and T cell receptor gene | RAG1 and RAG2 mutation analysis |
| Omenn's syndrome | ||||
| T cell receptor deficiencies (1987) | 11q23 | CD3γ/CD3ϵ | T cell receptor function and signalling | CD3 fluorescence intensity |
| Mutation analysis | ||||
| Zap70 deficiency (1994) | 2q12 | ZAP70 | T cell function; selection of CD8+ cells during thymocyte development | ZAP70 expression and activation |
| Mutation analysis | ||||
| JAK3 deficiency (T-B+NK− SCID) (1995) | 19p13 | JAK3 | IL-2, -4, -7, -9, -15 receptor signalling; T and NK cell development; T and B cell function | JAK3 expression/activation |
| Mutation analysis | ||||
| IL-7 receptor deficiency (1998) | 5p13 | IL-7 receptor α | Essential role in T cell development and function | IL-7α FACs expression |
| Mutation analysis | ||||
| II. Non-SCID | ||||
| Leucocyte adhesion deficiency type 1 (1987) | 21q22 | CD11/CD18 | Defective leucocyte adhesion and migration | CD11/CD18 expression by FACS analysis |
| Mutation analysis | ||||
| Chronic granulomatous disease (1990) | 7q11 | p47phox | Defective respiratory burst and phagocytic intracellular killing | p47phox, p67phox, p22phox expression by immunoblotting |
| 1990 | 1q25 | p67phox | ||
| 1988 | 16p24 | p22phox | Mutation analysis | |
| Chediak Higashi syndrome (1996) | 1q42 | LYST | Abnormalities in microtubule mediated lysosomal protein trafficking | Giant inclusions in granulocytes |
| Mutation analysis | ||||
| MHC class II deficiency (1993) | 16p13 | CIITA (MHC2TA) | Defective transcriptional regulation of MHCII molecule expression | HLA-DR expression |
| (1998) | 19p12 | RFXANK | Mutation analysis | |
| (1995) | 1q21 | RFX5 | ||
| (1997) | 13q13 | RFXAP | ||
| MHC class I deficiency (1994) | 6p21 | TAP2 | Defective peptide loading and presentation of HLA class I molecules | HLA class I expression |
| (1999) | 6p21 | TAP1 | ||
| Autoimmune lymphoproliferative syndrome (ALPS) (1995) | 10q24 | APT1 (Fas) | Defective apoptosis of lymphocytes | Fas expression |
| Apoptosis assays | ||||
| Mutation analysis | ||||
| Ataxia telangiectasia (1995) | 11q22 | ATM | Cell cycle control and DNA damage responses | DNA radiation sensitivity |
| Mutation analysis | ||||
| Inherited mycobacterial susceptibility | Defective γ interferon production and signalling function | Interferon γ receptor expression | ||
| (1996) | 6q23 | Interferon γ receptor | IL-12 expression | |
| (1998) | 5q31 | IL-12 p40 | IL-12 receptor expression | |
| (1998) | 19p13 | IL-12 receptor β1 | Mutation analysis | |