Table 2

Autosomal recessive immunodeficiencies

Disorder (year of definition of molecular basis)Chromosomal localisationGeneFunction/defectDiagnostic 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)20q12-13Adenosine deaminaseEnzyme in purine salvage pathway; accumulation of toxic metabolitesRed cell ADA levels and metabolites
Mutation analysis
Purine nucleoside phosphorylase (PNP) deficiency (1987)14q11Purine nucleoside phosphorylaseEnzyme in purine salvage pathway; accumulation of toxic metabolitesRed cell PNP levels and metabolites
Mutation analysis
Recombinase activating gene (RAG 1 and 2) deficiency (1996)11p13RAG1 and RAG2Defective DNA recombination affecting immunoglobulin and T cell receptor geneRAG1 and RAG2 mutation analysis
Omenn's syndrome
T cell receptor deficiencies (1987)11q23CD3γ/CD3ϵT cell receptor function and signallingCD3 fluorescence intensity
Mutation analysis
Zap70 deficiency (1994)2q12ZAP70T cell function; selection of CD8+ cells during thymocyte developmentZAP70 expression and activation
Mutation analysis
JAK3 deficiency (T-B+NK− SCID) (1995)19p13JAK3IL-2, -4, -7, -9, -15 receptor signalling; T and NK cell development; T and B cell functionJAK3 expression/activation
Mutation analysis
IL-7 receptor deficiency (1998)5p13IL-7 receptor αEssential role in T cell development and functionIL-7α FACs expression
Mutation analysis
Leucocyte adhesion deficiency type 1 (1987)21q22CD11/CD18Defective leucocyte adhesion and migrationCD11/CD18 expression by FACS analysis
Mutation analysis
Chronic granulomatous disease (1990)7q11p47phoxDefective respiratory burst and phagocytic intracellular killingp47phox, p67phox, p22phox expression by immunoblotting
198816p24p22phoxMutation analysis
Chediak Higashi syndrome (1996)1q42LYSTAbnormalities in microtubule mediated lysosomal protein traffickingGiant inclusions in granulocytes
Mutation analysis
MHC class II deficiency (1993)16p13CIITA (MHC2TA)Defective transcriptional regulation of MHCII molecule expressionHLA-DR expression
 (1998)19p12RFXANKMutation analysis
MHC class I deficiency (1994)6p21TAP2Defective peptide loading and presentation of HLA class I moleculesHLA class I expression
Autoimmune lymphoproliferative syndrome (ALPS) (1995)10q24APT1 (Fas)Defective apoptosis of lymphocytesFas expression
Apoptosis assays
Mutation analysis
Ataxia telangiectasia (1995)11q22ATMCell cycle control and DNA damage responsesDNA radiation sensitivity
Mutation analysis
Inherited mycobacterial susceptibilityDefective γ interferon production and signalling functionInterferon γ receptor expression
 (1996)6q23Interferon γ receptorIL-12 expression
 (1998)5q31IL-12 p40IL-12 receptor expression
 (1998)19p13IL-12 receptor β1Mutation analysis