This comprehensive panel includes more than 450 genes covering genetic disorders of the immune system. Defects in these genes can cause alterations in immunity. Due to the phenotypic overlap and complexity of these disorders, our broad approach to immunogenetics covers two major groups: Primary Immunodeficiencies (PID), including disorders of innate and adaptive immunity; and Immune Dysregulation Diseases (IDD), encompassing autoimmune and autoinflammatory disorders. In addition, the panel considers overlapping and syndromic conditions in these disorders.
Disorders of the immune system refer to a group of diseases in which a component of the immune system is not functional or functions improperly. To date, more than 450 distinct disorders have been described, each of which is characterized by a specific gene defect. Depending on the pathway in which the gene is involved, its defect may jeopardize the ability of the body to mount an immune response against an infecting agent (immune deficiency) or it may lead to an over-activation or dysregulation of the immune response (autoimmunity and inflammation). A primary immune deficiency can either be due to a failure of the cellular and humoral (adaptive) response or to a defect of intrinsic and innate immunity. Autoimmunity is a manifestation of a dysregulated adaptive immune response, mainly of T cells, whereas autoinflammation represents a dysregulation of innate immunity.
Many of these disorders have a combination of immunodeficiency and autoimmunity or autoinflammation, or they can be accompanied by additional syndromic features that affect other body systems. Moreover, the fine line between autoimmunity and autoinflammation makes it often difficult to discern between the two, although on occasion they are indeed intrinsically related. This intricacy makes the accurate diagnoses of these disorders a hard task in clinical practice, as symptoms often overlap and are often confounding.
Current estimates of the global prevalence of individuals affected by a disorder of the immune system are unknown. Some studies suggest that the prevalence of autoimmune diseases could be ~8%, with increasing incidence and prevalence every year. For primary immunodeficiencies (PID), recent epidemiological studies suggest that the prevalence might be more than 1 in 1,200 births and that up to 6 million people worldwide might be living with a PID.
Genetic testing has become essential for diagnosis and for understanding the nature of the disease. Accurate and early genetic diagnosis is essential to offer the patient the best available treatment to improve quality of life and thus reduce hospitalizations and disease-associated morbidity.
ABCB1, ACD, ACP5, ACTB, ADA, ADA2, ADAM17, ADAR, ADGRE2, AICDA, AIRE, AK2, ANXA11, AP3B1, AP3D1, APOL1, ARID5B, ARPC1B, ATG16L1, ATG5, ATM, ATP6AP1, B2M, BANK1, BCL10, BCL11B, BLK, BLM, BLNK, BTK, BTNL2, C1QA, C1QB, C1QC, C1QTNF4, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C8B, C8G, C9, CALCOCO2, CARD11, CARD14, CARD9, CARMIL2, CASP10, CASP8, CCBE1, CCDC88B, CCL2, CCL22, CCR1, CCR3, CCR5, CCR9, CD14, CD19, CD226, CD247, CD27, CD3D, CD3E, CD3G, CD40, CD40LG, CD46, CD55, CD59, CD70, CD79A, CD79B, CD81, CD8A, CDCA7, CEBPE, CFB, CFD, CFH, CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, CFI, CFP, CFTR, CHD7, CIITA, CLCN7, CLEC16A, CLEC7A, CLPB, CORO1A, CR2, CSF2RA, CSF2RB, CSF3R, CSK, CTC1, CTLA4, CTPS1, CTSC, CXCL13, CXCR4, CXCR5, CYBA, CYBB, DCLRE1B, DCLRE1C, DDX58, DGAT1, DGKE, DKC1, DNAJC21, DNASE1, DNASE1L3, DNMT3A, DNMT3B, DOCK2, DOCK8, E2F1 , EGFR, ELANE, EPCAM, EPG5, ERAP1, ERCC6L2, ETS1, EXTL3, F12, FAAP24, FADD, FAS, FASLG, FCGR2A, FCGR2B, FCGR3A, FCN3, FERMT3, FOXN1, FOXP3, FPR1, FUT2, G6PC3, G6PD, GATA1, GATA2, GFI1, GINS1, GUCY2C, HAS2, HAX1, HELLS, HMOX1, HNF1A, HYOU1, ICAM1, ICOS, IFIH1, IFNAR2, IFNGR1, IFNGR2, IGLL1, IKBKB, IKBKG, IKZF1, IKZF3, IL10, IL10RA, IL10RB, IL12A, IL12B, IL12RB1, IL12RB2, IL15, IL15RA, IL17F, IL17RA, IL17RC, IL18R1, IL1RN, IL21, IL21R, IL23A, IL23R, IL2RA, IL2RG, IL36RN, IL7R, INO80, IRAK1, IRAK4, IRF1, IRF2BP2, IRF3, IRF5, IRF7, IRF8, IRGM, ISG15, ITCH, ITGAM, ITGB2, ITK, JAGN1, JAK1, JAK3, KDM6A, KIRREL2, KLRC4, KMT2D, KRAS, LACC1, LAMTOR2, LAT, LCK, LIG1, LIG4, LIMK2, LPIN2, LRBA, LRRC8A, LYST, MAGT1, MALT1, MAN2B1, MAP3K14, MASP1, MASP2, MBL2, MC2R, MC3R, MCM2, MCM4, MECP2, MEFV, MICA, MICB, MKL1, MME, MOGS, MPO, MRAP, MRC1, MS4A1, MSH6, MSN, MST1, MTHFD1, MTHFR, MTMR3, MVK, MYD88, MYH9, MYO5A, MYO5B, MYSM1, NBAS, NBN, NCF1, NCF2, NCF4, NCSTN, NEIL1, NEUROG3, NFAT5 , NFKB1, NFKB2, NFKBIA, NHEJ1, NHP2, NLRC4, NLRP12, NLRP3, NOD2, NOP10, NPHS1, NR0B1, NR4A2, NRAS, NSMCE3, OAS1, OAS2, ORAI1, OSTM1, OTULIN, PARN, PBX1, PDCD1, PDGFRA, PEPD, PGM3, PHF11, PIK3CD, PIK3R1, PLA2R1, PLCG2, PLEKHM1, PMS2, PNP, POLE, POLE2, PRDM1, PRF1, PRKCD, PRKDC, PRKG1, PRPS1, PSEN1, PSENEN, PSMB8, PSTPIP1, PTEN, PTGS2, PTPN2, PTPN22, PTPRC, PXK, RAB27A, RAC2, RAG1, RAG2, RANBP2, RASGRP1, RBCK1, RECQL4, REL, RELB, RFX5, RFXANK, RFXAP, RHOH, RMRP, RNASEH2A, RNASEH2B, RNASEH2C, RNF168, RNF31, RNU4ATAC, RORC, RPSA, RTEL1, SAA1, SAMD9, SAMD9L, SAMHD1, SATB1, SBDS, SEC61A1, SEMA3E, SERPING1, SH2D1A, SKIV2L, SLC11A1, SLC26A3, SLC35C1, SLC37A4, SLC46A1, SLC7A7, SLC9A3, SMARCAL1, SMARCD2, SNX10, SP110, SPATA5, SPINK5, SPINT2, STAT1, STAT2, STAT3, STAT4, STAT5B, STAT6, STIM1, STK4, STN1, STX11, STXBP2, TAGAP, TAP1, TAP2, TAPBP, TAZ, TBK1, TBX1, TBX21, TCF3, TCF7, TCIRG1, TCN2, TERC, TERT, TFRC , TGFB1, THBD, THBS1, THSD7A, TICAM1, TINF2, TIRAP, TLR1, TLR2, TLR3, TLR5, TLR7, TLR8, TLR9, TMC6, TMC8, TMEM173, TNF, TNFAIP3, TNFRSF11A, TNFRSF13B, TNFRSF13C, TNFRSF1A, TNFRSF4, TNFSF11, TNFSF12, TNFSF13 , TNFSF15, TNFSF4, TNIP1, TRAF3, TRAF3IP2, TREX1, TRIM21, TRNT1, TTC37, TTC7A, TYK2, UBAC2, UBE2L3, UHRF1BP1, UNC119, UNC13D, UNC93B1, UNG, USB1, VPS13B, VPS45, WAS, WDR1, WIPF1, WRAP53, XIAP, XKR6, ZAP70, ZBTB24, ZNF341