Primary immunodeficiency diseases comprise a heterogeneous group of more than 300 distinct hereditary disorders, each of them caused by a different gene defect. Our panel includes those genes that have been associated with a defective adaptive or innate immune response, either by causing a specific or combined B or T cell deficiency, a particular defect of phagocytes or host defences, or a deficiency of the complement system. Clinical manifestations are highly variable; however, most affected individuals share an increased vulnerability to infections affecting various body systems. The estimated prevalence of PID is about 1 in 1,200 births. The complexity and symptom overlap found in PID makes genetic testing essential for the understanding and diagnosis of the disease and for the management of the patient.
Human primary immunodeficiency diseases (PID) comprise a heterogeneous group of more than 300 distinct hereditary disorders, each of them caused by a different gene defect. Depending on which gene is altered, a different molecular pathway, cell population, or type of immune response will be affected. Our panel includes those genes in which variants have been associated with an abnormal hematopoietic or nonhematopoietic host defense, either by causing a specific or a combined cellular and humoral deficiency, a particular defect of phagocytes or host defences, or a deficiency of the complement system.
Clinical manifestations of PID are highly variable; however, most affected individuals share an increased vulnerability to infection that can manifest as recurrent, persistent, or unusually severe infections. These infections may start early in life and affect the respiratory, urinary or intestinal tract, skin, ears, and nervous system. Many PIDs are complicated by autoimmunity or chronic inflammation and/or lymphoproliferation. Strong epidemiological evidence underlines the importance of genetic background in predisposition to infections, suggesting that any severe infectious illness may be considered a potential PID-defining phenotype. PID may present with additional complications, such as autoimmunity, inflammation, allergy, malignancy or syndromic features.
Although PIDs have long been considered rare, they are more common than generally thought and are usually under-diagnosed. Recent epidemiological studies suggest that the overall prevalence of PID might range from 1:1,200 to 1:10,000 births and that up to 6 million people worldwide might be living with a PID. However, the most common PID, which is immunoglobulin A (IgA) deficiency, has a prevalence of 1 in 300-500 births.
Genetic testing has become essential for diagnosis and for understanding the nature of the disease. Since some PIDs may be fatal, early and accurate 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.
ACD, ACP5, ACTB, ADA, ADA2, AICDA, AIRE, AK2, AP3B1, AP3D1, APOL1, ARPC1B, ATM, ATP6AP1, B2M, BCL10, BCL11B, BLM, BLNK, BTK, C1QA, C1QB, C1QC, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C8B, C8G, C9, CARD11, CARD9, CARMIL2, CASP8, CCBE1, CCL2, CD19, CD247, CD27, CD3D, CD3E, CD3G, CD40, CD40LG, CD46, CD55, CD59, CD79A, CD79B, CD81, CD8A, CDCA7, CEBPE, CFB, CFD, CFH, CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, CFI, CFP, CFTR, CHD7, CIITA, CLCN7, CLEC7A, CLPB, CORO1A, CR2, CSF2RA, CSF2RB, CSF3R, CTC1, CTLA4, CTPS1, CTSC, CXCR4, CYBA, CYBB, DCLRE1B, DCLRE1C, DGKE, DKC1, DNAJC21, DNMT3B, DOCK2, DOCK8, ELANE, EPG5, ERCC6L2, EXTL3, F12, FCGR3A, FCN3, FERMT3, FOXN1, FOXP3, FPR1, G6PC3, G6PD, GATA1, GATA2, GFI1, GINS1, HAX1, HELLS, HMOX1, HYOU1, ICOS, IFIH1, IFNAR2, IFNGR1, IFNGR2, IGLL1, IKBKB, IKBKG, IKZF1, IL10, IL10RA, IL10RB, IL12B, IL12RB1, IL17F, IL17RA, IL17RC, IL21, IL21R, IL2RA, IL2RG, IL7R, INO80, IRAK1, IRAK4, IRF2BP2, IRF3, IRF7, IRF8, ISG15, ITGB2, JAGN1, JAK1, JAK3, KDM6A, KMT2D, LAMTOR2, LAT, LCK, LIG1, LIG4, LRBA, LRRC8A, LYST, MAGT1, MALT1, MAP3K14, MASP1, MASP2, MBL2, MC3R, MCM2, MCM4, MKL1, MOGS, MPO, MRC1, MS4A1, MSH6, MSN, MTHFD1, MYD88, MYSM1, NBAS, NBN, NCF1, NCF2, NCF4, NCSTN, NFAT5 , NFKB1, NFKB2, NFKBIA, NHEJ1, NHP2, NOD2, NOP10, NSMCE3, ORAI1, OSTM1, PARN, PGM3, PHF11, PIK3CD, PIK3R1, PLCG2, PLEKHM1, PMS2, PNP, POLE, POLE2, PRKDC, PRPS1, PSEN1, PSENEN, PTEN, PTPRC, RAC2, RAG1, RAG2, RANBP2, RBCK1, REL, RELB, RFX5, RFXANK, RFXAP, RHOH, RMRP, RNF168, RNF31, RNU4ATAC, RORC, RPSA, RTEL1, SAMD9, SAMD9L, SBDS, SEC61A1, SEMA3E, SERPING1, SLC11A1, SLC35C1, SLC37A4, SLC46A1, SMARCAL1, SMARCD2, SNX10, SP110, SPATA5, SPINK5, STAT1, STAT2, STAT3, STAT5B, STIM1, STK4, STN1, TAP1, TAP2, TAPBP, TAZ, TBK1, TBX1, TCF3, TCIRG1, TCN2, TERC, TERT, TFRC , THBD, TICAM1, TINF2, TIRAP, TLR1, TLR2, TLR3, TMC6, TMC8, TNFRSF11A, TNFRSF13B, TNFRSF13C, TNFRSF4, TNFSF11, TNFSF12, TNFSF13 , TRAF3, TRAF3IP2, TRNT1, TTC37, TTC7A, TYK2, UNC119, UNC93B1, UNG, USB1, VPS13B, VPS45, WAS, WDR1, WIPF1, WRAP53, ZAP70, ZBTB24, ZNF341