Targeted capture panel of genes associated with IEIs (n = 374), constitutional cytopenia (n = 21), and other monogenic disorders (n = 179)
| IEIs . | |
|---|---|
| Immunodeficiencies affecting cellular and humoral immunity | ADA, AK2, B2M, BCL10, CARD11, CD247, CD3D, CD3E, CD3G, CD40, CD40LG, CD8A, CIITA, CORO1A, DCLRE1C, DOCK2, DOCK8, FCHO1, ICOS, ICOSLG, IKBKB, IL21, IL21R, IL2RG, IL7R, IKZF1, ITK, JAK3, LAT, LCK, LIG4, MALT1, MAP3K14, MSN, NHEJ1, PAX1, POLD1, POLD2, PRKDC, PTPRC, RAG1, RAG2, REL, RELA, RELB, RFX5, RFXANK, RFXAP, RHOH, STK4, TAP1, TAP2, TAPBP, TFRC, TNFRSF4, and ZAP70 |
| Combined immunodeficiencies with associated or syndromic features | ARPC1B, ATM, BCL11B, BLM, CCBE1, CDCA7, CHD7, DNMT3B, EPG5, ERBIN, EXTL3, FAT4, FOXN1, GINS1, HELLS, IL6R, IL6ST, KDM6A, KMT2A, KMT2D, LIG1, MCM4, MTHFD1, MYSM1, NBN, NFE2L2, NFKBIA, NSMCE3, ORAI1, PGM3, PMS2, PNP, POLE, POLE2, RBCK1, RMRP, RNF168, RNF31, RNU4ATAC, SEMA3E, SKIV2L, SLC46A1, SMARCAL1, SP110, SPINK5, STAT3, STAT5B, STIM1, TBX1, TCN2, TGFBR1, TGFBR2, TTC37, TTC7A, WIPF1, ZBTB24, and ZNF341 |
| Predominantly antibody deficiencies | AICDA, ARHGEF1, ATP6AP1, BLNK, BTK, CD19, CD79A, CD79B, CD81, CR2, FNIP1, IGLL1, IRF2BP2, MOGS, MS4A1, MSH6, NFKB1, NFKB2, PIK3CD, PIK3R1, PTEN, SEC61A1, SH3KBP1, SLC39A7, TCF3, TNFRSF13B, TNFRSF13C, TNFSF12, TOP2B, TRNT1, and UNG |
| Diseases of immune dysregulation | AIRE, AP3B1, AP3D1, BACH2, CARMIL2, CASP10, CASP8, CD27, CEBPE, CTLA4, CTPS1, DEF6, FADD, FAS, FASLG, FERMT1, FOXP3, IL10, IL10RA, IL10RB, IL2RA, IL2RB, ITCH, LRBA, LYST, MAGT1, NFAT5, PEPD, PRF1, PRKCD, RAB27A, RASGRP1, RIPK1, SH2D1A, SLC7A7, STX11, STXBP2, TET2, TGFB1, TNFRSF9, TPP2, UNC13D, and XIAP |
| Congenital defects of phagocyte number or function | ACTB, CFTR, CLPB, CSF2RA, CSF2RB, CSF3R, CTSC, CXCR2, CYBA, CYBB, EFL1, ELANE, FERMT3, FPR1, G6PC3, G6PD, GATA2, GFI1, HAX1, HYOU1, ITGB2, JAGN1, LAMTOR2, MKL1, NCF2, NCF4, RAC2, SLC35C1, SLC37A4, SMARCD2, SRP54, TAZ, USB1, VPS13B, VPS45, WAS, and WDR1 |
| Defects in intrinsic and innate immunity | CARD9, CIB1, CLCN7, CXCR4, DBR1, HMOX1, IFIH1, IFNAR1, IFNAR2, IFNGR1, IFNGR2, IL12B, IL12RB1, IL12RB2, IL17F, IL17RA, IL17RC, IL23R, IL18BP, IRAK4, IRF4, IRF7, IRF8, IRF9, ISG15, JAK1, MYD88, NBAS, NCSTN, OSTM1, POLR3A, POLR3F, PSENEN, RANBP2, RORC, RPSA, SNX10, SPPL2A, STAT1, STAT2, TCIRG1, TICAM1, TLR3, TLR7, TMC6, TMC8, TNFRSF11A, TNFSF11, TRAF3, TRAF3IP2, TYK2, and UNC93B1 |
| Autoinflammatory disorders | ACP5, ADA2, ADAM17, ADAR, CARD14, CDC42, COPA, DNASE1L3, DNASE2, IL1RN, IL36RN, LPIN2, MEFV, MVK, NCKAP1L, NLRC4, NLRP1, NLRP12, NLRP3, NOD2, OAS1, OTULIN, PLCG2, POLA1, PSMB8, PSMG2, PSTPIP1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, SH3BP2, SLC29A3, TMEM173, TNFAIP3, TNFRSF1A, and TREX1 |
| Complement deficiencies | C1QA, C1QB, C1QC, C1S, C2, C3, C5, C6, C7, C8A, C8B, C9, CD46, CD55, CD59, CFB, CFD, CFH, CFI, CFP, SERPING1, and THBD |
| Bone marrow failure | ACD, BRCA1, BRCA2, BRIP1, CTC1, DKC1, DNAJC21, ERCC4, ERCC6L2, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, MAD2L2, NOP10, PALB2, PARN, RAD51, RAD51C, RFWD3, RTEL1, SAMD9, SAMD9L, SLX4, SRP72, STN1, TERC, TERT, TINF2, TP53, UBE2T, WRAP53, and XRCC2 |
| IEIs . | |
|---|---|
| Immunodeficiencies affecting cellular and humoral immunity | ADA, AK2, B2M, BCL10, CARD11, CD247, CD3D, CD3E, CD3G, CD40, CD40LG, CD8A, CIITA, CORO1A, DCLRE1C, DOCK2, DOCK8, FCHO1, ICOS, ICOSLG, IKBKB, IL21, IL21R, IL2RG, IL7R, IKZF1, ITK, JAK3, LAT, LCK, LIG4, MALT1, MAP3K14, MSN, NHEJ1, PAX1, POLD1, POLD2, PRKDC, PTPRC, RAG1, RAG2, REL, RELA, RELB, RFX5, RFXANK, RFXAP, RHOH, STK4, TAP1, TAP2, TAPBP, TFRC, TNFRSF4, and ZAP70 |
| Combined immunodeficiencies with associated or syndromic features | ARPC1B, ATM, BCL11B, BLM, CCBE1, CDCA7, CHD7, DNMT3B, EPG5, ERBIN, EXTL3, FAT4, FOXN1, GINS1, HELLS, IL6R, IL6ST, KDM6A, KMT2A, KMT2D, LIG1, MCM4, MTHFD1, MYSM1, NBN, NFE2L2, NFKBIA, NSMCE3, ORAI1, PGM3, PMS2, PNP, POLE, POLE2, RBCK1, RMRP, RNF168, RNF31, RNU4ATAC, SEMA3E, SKIV2L, SLC46A1, SMARCAL1, SP110, SPINK5, STAT3, STAT5B, STIM1, TBX1, TCN2, TGFBR1, TGFBR2, TTC37, TTC7A, WIPF1, ZBTB24, and ZNF341 |
| Predominantly antibody deficiencies | AICDA, ARHGEF1, ATP6AP1, BLNK, BTK, CD19, CD79A, CD79B, CD81, CR2, FNIP1, IGLL1, IRF2BP2, MOGS, MS4A1, MSH6, NFKB1, NFKB2, PIK3CD, PIK3R1, PTEN, SEC61A1, SH3KBP1, SLC39A7, TCF3, TNFRSF13B, TNFRSF13C, TNFSF12, TOP2B, TRNT1, and UNG |
| Diseases of immune dysregulation | AIRE, AP3B1, AP3D1, BACH2, CARMIL2, CASP10, CASP8, CD27, CEBPE, CTLA4, CTPS1, DEF6, FADD, FAS, FASLG, FERMT1, FOXP3, IL10, IL10RA, IL10RB, IL2RA, IL2RB, ITCH, LRBA, LYST, MAGT1, NFAT5, PEPD, PRF1, PRKCD, RAB27A, RASGRP1, RIPK1, SH2D1A, SLC7A7, STX11, STXBP2, TET2, TGFB1, TNFRSF9, TPP2, UNC13D, and XIAP |
| Congenital defects of phagocyte number or function | ACTB, CFTR, CLPB, CSF2RA, CSF2RB, CSF3R, CTSC, CXCR2, CYBA, CYBB, EFL1, ELANE, FERMT3, FPR1, G6PC3, G6PD, GATA2, GFI1, HAX1, HYOU1, ITGB2, JAGN1, LAMTOR2, MKL1, NCF2, NCF4, RAC2, SLC35C1, SLC37A4, SMARCD2, SRP54, TAZ, USB1, VPS13B, VPS45, WAS, and WDR1 |
| Defects in intrinsic and innate immunity | CARD9, CIB1, CLCN7, CXCR4, DBR1, HMOX1, IFIH1, IFNAR1, IFNAR2, IFNGR1, IFNGR2, IL12B, IL12RB1, IL12RB2, IL17F, IL17RA, IL17RC, IL23R, IL18BP, IRAK4, IRF4, IRF7, IRF8, IRF9, ISG15, JAK1, MYD88, NBAS, NCSTN, OSTM1, POLR3A, POLR3F, PSENEN, RANBP2, RORC, RPSA, SNX10, SPPL2A, STAT1, STAT2, TCIRG1, TICAM1, TLR3, TLR7, TMC6, TMC8, TNFRSF11A, TNFSF11, TRAF3, TRAF3IP2, TYK2, and UNC93B1 |
| Autoinflammatory disorders | ACP5, ADA2, ADAM17, ADAR, CARD14, CDC42, COPA, DNASE1L3, DNASE2, IL1RN, IL36RN, LPIN2, MEFV, MVK, NCKAP1L, NLRC4, NLRP1, NLRP12, NLRP3, NOD2, OAS1, OTULIN, PLCG2, POLA1, PSMB8, PSMG2, PSTPIP1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, SH3BP2, SLC29A3, TMEM173, TNFAIP3, TNFRSF1A, and TREX1 |
| Complement deficiencies | C1QA, C1QB, C1QC, C1S, C2, C3, C5, C6, C7, C8A, C8B, C9, CD46, CD55, CD59, CFB, CFD, CFH, CFI, CFP, SERPING1, and THBD |
| Bone marrow failure | ACD, BRCA1, BRCA2, BRIP1, CTC1, DKC1, DNAJC21, ERCC4, ERCC6L2, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, MAD2L2, NOP10, PALB2, PARN, RAD51, RAD51C, RFWD3, RTEL1, SAMD9, SAMD9L, SLX4, SRP72, STN1, TERC, TERT, TINF2, TP53, UBE2T, WRAP53, and XRCC2 |
| Constitutional cytopenia . |
|---|
| ABCG5, ABCG8, ACTN1, ANKRD26, BLOC1S6, CDAN1, CYCS, DIAPH1, ETV6, FLI1, GATA1, GP1BA, GP6, GP9, ITGA2B, ITGB3, MECOM, MPL, MYH9, RBM8A, RUNX1, THPO, TUBB1, VIPAS39, and VPS33B |
| Constitutional cytopenia . |
|---|
| ABCG5, ABCG8, ACTN1, ANKRD26, BLOC1S6, CDAN1, CYCS, DIAPH1, ETV6, FLI1, GATA1, GP1BA, GP6, GP9, ITGA2B, ITGB3, MECOM, MPL, MYH9, RBM8A, RUNX1, THPO, TUBB1, VIPAS39, and VPS33B |
| Miscellaneous . |
|---|
| ABCB7, ACAN, ADAMTS13, ADGRE2, AK7, ALAS2, ALG6, ALPK1, ANGPT1, ANKZF1, ANO6, ARMC4, ASAH1, ATR, BLOC1S3, C11orf70, C15orf41, C17orf62, CARD8, CBL, CCDC103, CCDC114, CCDC151, CCDC39, CCDC40, CCDC65, CCNO, CEP164, CFAP298, CHEK2, COL7A1, CYP27A1, DDX41, DDX58, DGAT1, DGKE, DNAAF1, DNAAF2, DNAAF3, DNAAF4, DNAAF5, DNAH1, DNAH11, DNAH5, DNAH8, DNAH9, DNAI1, DNAI2, DNAJB13, DNAL1, DRC1, DSG1, DTNBP1, DUOX2, EIF2AK3, EPCAM, ERCC2, ERCC3, FOXI3, G6PC, GAS8, GLRX5, GTF2H5, GTF2E2, GUCY2C, HPS1, HPS3, HPS4, HPS5, HPS6, HTRA2, ITGAM, JAK2, KAT6A, KDM1A, KIF23, KIT, KLF1, KLHDC8B, LARS2, LCT, LIPA, LRRC56, LRRC6, LRRC8A, LYN, MBD4, MCIDAS, MLH1, MPLKIP, MSH2, MYO5B, NAF1, NDUFB11, NEUROG3, NF1, NHP2, NME8, NPAT, NOTCH2, OFD1, P2RY12, PIH1D3, PLA2G4A, PLG, PLVAP, PMM2, PNLIP, POMP, POT1, PSMA3, PSMB4, PUS1, RASGRP2, RECQL4, RNF113A, RPGR, RPL11, RPL15, RPL18, RPL19, RPL23, RPL26, RPL27, RPL31, RPL35, RPL35A, RPL5, RPL9, RPS10, RPS15A, RPS19, RPS24, RPS26, RPS27, RPS28, RPS29, RPS7, RSPH1, RSPH3, RSPH4A, RSPH9, SAR1B, SBF2, SCO2, SEC23B, SGPL1, SI, SIAE, SLC10A2, SLC19A2, SLC25A38, SLC26A3, SLC5A1, SLC51B, SLC9A3, SPAG1, SPINT2, STAT4, STX3, TAOK2, TBXA2R, TERF2IP, TIMM50, TMPRSS15, TNFRSF6B, TONSL, TP63, TSR2, UNC45A, VAV1, WNT2B, YARS2, ZCCHC8, and ZMYND10 |
| Miscellaneous . |
|---|
| ABCB7, ACAN, ADAMTS13, ADGRE2, AK7, ALAS2, ALG6, ALPK1, ANGPT1, ANKZF1, ANO6, ARMC4, ASAH1, ATR, BLOC1S3, C11orf70, C15orf41, C17orf62, CARD8, CBL, CCDC103, CCDC114, CCDC151, CCDC39, CCDC40, CCDC65, CCNO, CEP164, CFAP298, CHEK2, COL7A1, CYP27A1, DDX41, DDX58, DGAT1, DGKE, DNAAF1, DNAAF2, DNAAF3, DNAAF4, DNAAF5, DNAH1, DNAH11, DNAH5, DNAH8, DNAH9, DNAI1, DNAI2, DNAJB13, DNAL1, DRC1, DSG1, DTNBP1, DUOX2, EIF2AK3, EPCAM, ERCC2, ERCC3, FOXI3, G6PC, GAS8, GLRX5, GTF2H5, GTF2E2, GUCY2C, HPS1, HPS3, HPS4, HPS5, HPS6, HTRA2, ITGAM, JAK2, KAT6A, KDM1A, KIF23, KIT, KLF1, KLHDC8B, LARS2, LCT, LIPA, LRRC56, LRRC6, LRRC8A, LYN, MBD4, MCIDAS, MLH1, MPLKIP, MSH2, MYO5B, NAF1, NDUFB11, NEUROG3, NF1, NHP2, NME8, NPAT, NOTCH2, OFD1, P2RY12, PIH1D3, PLA2G4A, PLG, PLVAP, PMM2, PNLIP, POMP, POT1, PSMA3, PSMB4, PUS1, RASGRP2, RECQL4, RNF113A, RPGR, RPL11, RPL15, RPL18, RPL19, RPL23, RPL26, RPL27, RPL31, RPL35, RPL35A, RPL5, RPL9, RPS10, RPS15A, RPS19, RPS24, RPS26, RPS27, RPS28, RPS29, RPS7, RSPH1, RSPH3, RSPH4A, RSPH9, SAR1B, SBF2, SCO2, SEC23B, SGPL1, SI, SIAE, SLC10A2, SLC19A2, SLC25A38, SLC26A3, SLC5A1, SLC51B, SLC9A3, SPAG1, SPINT2, STAT4, STX3, TAOK2, TBXA2R, TERF2IP, TIMM50, TMPRSS15, TNFRSF6B, TONSL, TP63, TSR2, UNC45A, VAV1, WNT2B, YARS2, ZCCHC8, and ZMYND10 |
The panel was expanded from 473 to 574 genes during the study, with the added genes denoted by underlining. Twenty-three patients (56%) underwent testing on the 574-gene panel.