Klinisk Immulologisk Afdeling, Odense Universitetshospital
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Primær immundefekt, genetisk udredning (fuldgenomsekventering)
Analysekomponent
Primær immundefekt, genetisk udredning (fuldgenomsekventering).
IUPAC kode
Ikke defineret
Indikation
Formodning om primær immundefekt.
Prøvemateriale
Antikoaguleret fuldblod (EDTA)/celler/DNA
Opbevarin, holdbarhed og forsendelse
Ingen specifikke krav.
Indleveringsfrister
Udføres efter aftale.
Tlf. ved forespørgsler
2142 2696/5182 9948
Tolkning
Analysen er udført med fuldgenomsekventering (engelsk: whole genome sequencing, WGS). For singleton-analyser (kun probandens gener analyseres) bliver der filtreret, så der alene analyseres for varianter i 845 gener, der er associeret til primær immundefekt. For trio-analyser vil de novo, compound-heterozygote samt homozygote varianter hvor forældre er heterozygote i tillæg blive analyseret. I trioanalyser analyseres også gener, der ikke indgår i primær immundefekt-genpanelet. Ved fuldgenomsekventering vil der ikke være 100 % dækning af alle kodende regioner i alle gener. Middelsekventeringsdybden for hele genomet vil minimum være på 30 reads.
Varianter klassificeres som C1, C2, C3, C4 og C5 efter kriterier defineret i American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology's gældende guideline (Richards et al, 2015. PMID. 25741868). Varianter der anses for værende uden klinisk betydning vil ikke blive rapporteret.
Negative fund vil blive afrapporteret som en liste af gener, hvor de kodende regioner samt de flankerende 10 bp af introns er dækket 100%.
Primær immundefekt genpanel (845 gener):
ABCB1, ABCC6, ABCG5, ABCG8, ABI3, ACD, ACKR1, ACP5, ACTB, ACTN1, ADA, ADA2, ADAM17, ADAMTS13, ADAMTS2, ADAR, ADIPOQ, ADIPOR1, ADIPOR2, AGPAT2, AGPS, AGR2, AICDA, AIRE, AK2, ALPI, ALPK1, AMN, ANGPT1, ANKRD26, ANKZF1, ANO6, ANTXR2, AP1S3, AP3B1, AP3D1, APOL1, ARHGAP42, ARHGEF1, ARMC4, ARPC1B, ARPC5, ATAD3A, ATG4A, ATM, ATP6AP1, ATP6V0A2, ATP7A, ATP7B, B2M, BACH2, BCL10, BCL11B, BLM, BLNK, BLOC1S3, BLOC1S6, BRCA1, BRCA2, BTK, C11ORF70, C17ORF62, C1QA, C1QB, C1QBP, C1QC, C1R, C1S, C2, C21ORF59, C2orf69, C3, C3AR1, C4A, C4B, C4BPA, C4BPB, C5, C5AR1, C5AR2, C6, C7, C8A, C8B, C8G, C9, CAPG, CARD10, CARD11, CARD14, CARD8, CARD9, CARMIL2, CASP1, CASP10, CASP8, CBLB, CCBE1, CCDC103, CCDC114, CCDC151, CCDC39, CCDC40, CCDC65, CCNO, CD19, CD247, CD27, CD28, CD36, CD3D, CD3E, CD3G, CD4, CD40, CD40LG, CD46, CD55, CD59, CD70, CD79A, CD79B, CD81, CD8A, CD93, CDC42, CDCA7, CDK9, CEBPE, CECR1, CENPF, CFAP298, CFAP300, CFAP57, CFB, CFD, CFH, CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, CFI, CFP, CFTR, CHD7, CHUK, CIB1, CIITA, CLCN7, CLEC7A, CLPB, CLU, CNBP, COG6, COL1A1, COL1A2, COL3A1, COL4A3, COL4A4, COL4A5, COL5A1, COL5A2, COL7A1, COLEC11, COPA, COPG1, CORO1A, CR2, CRACR2A, CREBBP, CRP, CSF2, CSF2RA, CSF2RB, CSF3R, CSTA, CTC1, CTLA4, CTNNBL1, CTPS1, CTSC, CXCL10, CXCR2, CXCR4, CXorf36, CYBA, CYBB, CYBC1, CYCS, CYP27A1, DBR1, DCLRE1B, DCLRE1C, DDX41, DDX58, DEF6, DGAT1, DGKE, DIAPH1, DKC1, DNAH1, DNAH11, DNAH5, DNAH8, DNAH9, DNAI1, DNAI2, DNAJB13, DNAJC21, DNAL1, DNASE1L3, DNASE2, DNMT3B, DNAAF1, DNAAF11, DNAAF2, DNAAF3, DNAAF4, DNAAF5, DNAAF6, DOCK11, DOCK2, DOCK8, DRC1, DSG1, DTNBP1, DUOX2, DUT, DYX1C1, ECM1, EDA, EFEMP2, EFL1, EGFR, ELANE, ELF4, ELN, EPCAM, EPG5, ERBIN, ERCC2, ERCC3, ERCC4, ERCC6L2, ETV6, EXTL3, EZR, F12, F2R, F2RL3, FADD, FANCA, FANCF, FANCI, FANCM, FAS, FASLG, FAT4, FBF1, FBLN5, FBRS, FCGR1A, FCGR2A, FCGR2B, FCGR3A, FCGR3B, FCGRT, FCHO1, FCN1, FCN2, FCN3, FDPS, FERMT1, FERMT3, FGF23, FGL2, FLG, FLI1, FLI1 , FLNA, FLT4, FMNL2, FMO3, FNIP1, FOXC2, FOXI3, FOXJ1, FOXM1, FOXN1, FOXP3, FPR1, FPR2, FPR3, FYB, FYB1, FAAP24, G6PC, G6PC1, G6PC3, G6PD, GAD1, GALE, GALNT3, GAS2L2, GAS8, GATA1, GATA2, GBA, GFI1, GFI1B, GGCX, GIMAP5, GIMAP6, GINS1, GJA1, GJB3, GJB4, GNB1, GNE, GP1BA, GP1BB, GP6, GP9, GPI, GTF2H5, GUCY2C, HAVCR2, HAX1, HCK, HELLS, HMOX1, HOXA11, HPS1, HPS3, HPS4, HPS5, HPS6, HPS7, HPS8, HPS9, HS3ST6, HSPA1L, HTR1A, HTRA2, HYDIN, HYOU1, ICOS, ICOSLG, IFIH1, IFNAR1, IFNAR2, IFNG, IFNGR1, IFNGR2, IGHG2, IGHM, IGKC, IGLL1, IKBKB, IKBKG, IKZF1, IKZF2, IKZF3, IKZF5 , IL10, IL10RA, IL10RB, IL12B, IL12RB1, IL12RB2, IL17A, IL17F, IL17RA, IL17RB, IL17RC, IL18, IL18BP, IL1RN, IL21, IL21R, IL22, IL23A, IL23R, IL2RA, IL2RB, IL2RG, IL31RA, IL36RN, IL37, IL6, IL6R, IL6ST, IL7, IL7R, INAVA, INO80, INVS, IPO8, IRAK1, IRAK4, IRF2BP2, IRF3, IRF4, IRF7, IRF8, IRF9, IRGM, ISCA-37433-Loss, ISCA-37446-Loss, ISG15, ITCH, ITGA2, ITGA2B, ITGAM, ITGB2, ITGB3, ITK, ITPKB, ITPKC, IVNS1ABP, JAGN1, JAK1, JAK3, KCNA5, KDM6A, KDSR, KDSR , KIF23, KIT, KLF1, KMT2A, KMT2D, KRAS, KRT1, KRT10, LACC1, LAMTOR2, LAT, LCK, LCP2, LIG1, LIG4, LPIN2, LRBA, LRRC32, LRRC56, LRRC6, LRRC8A, LSM11, LTV1, LYN, LYST, LYZ, MAGT1, MALT1, MAN2B2, MAP1LC3B2, MAP3K14, MAPK8, MASP1, MASP2, MASTL, MAT2A, MBL2, MCIDAS, MCM10, MCM4, MCTS1, MECOM, MED13L, MEFV, MICA, MKL1, MLPH, MMACHC, MOGS, MPEG1, MPI, MPIG6B, MPL, MPO, MR1, MRE11, MRE11A, MS4A1, MS4A2, MSH6, MSN, MTHFD1, MTPAP, MVD, MVK, MYD88, MYH9, MYO5A, MYO5B, MYOF, MYSM1, NBAS, NBEA, NBEAL2, NBN, NCF1, NCF2, NCF4, NCKAP1L, NCSTN, NEK10, NFAT5, NFE2L2, NFKB1, NFKB2, NFKBIA, NFKBID, NHEJ1, NHP2, NLRC4, NLRP1, NLRP12, NLRP3, NLRP7, NME8, NOD2, NOP10, NOS2, NOX1, NPC1, NPM1, NRAS, NSDHL, NSMCE3, OAS1, OBFC1, ODAD1, ODAD2, ODAD3, ODAD4, ODC1, OFD1, OGFRL1, OPLAH, ORAI1, OSMR, OSTM1, OTULIN, P2RY1, P2RY12, PALB2, PARN, PARP1, PAX1, PCCA, PCCB, PDCD1, PEPD, PGM3, PI3K, PI4KA, PIGA, PIH1D3, PIK3CD, PIK3CG, PIK3R1, PLA2G4A, PLA2G7, PLAU, PLCG2, PLEKHM1, PLG, PMM2, PMS2, PNP, POLA1, POLD1, POLD2, POLD3, POLE, POLE2, POLR2C, POLR3A, POLR3C, POLR3F, POMP, POU2AF1, PRF1, PRG4, PRIM1, PRKACG, PRKCD, PRKDC, PRPS1, PSEN1, PSENEN, PSMA2, PSMA3, PSMB10, PSMB4, PSMB8, PSMB9, PSMG2, PSTPIP1, PTCRA, PTEN, PTGS1, PTPN11, PTPN2, PTPN22, PTPRC, PTX3, RAB27A, RAC2, RAD50, RAD51, RAD51C, RAG1, RAG2, RANBP2, RAP1B, RASGRP1, RASGRP2, RBCK1, RBM8A, RC3H1, RECQL4, REL, RELA, RELB, RELN, RET, RFWD3, RFX5, RFXANK, RFXAP, RGS10, RHBDF2, RHOG, RHOH, RIPK1, RLTPR, RMRP, RNASEH2A, RNASEH2B, RNASEH2C, RNF168, RNF31, RNU12, RNU4ATAC, RNU7-1, RORC, RPA1, RPGR, RPL11, RPL15, RPL18, RPL26, RPL27, RPL31, RPL35A, RPL5, RPL9, RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS27, RPS28, RPS29, RPS7, RPSA, RRAS, RSPH1, RSPH3, RSPH4A, RSPH9, RTEL1, RUNX1, SAMD3, SAMD9, SAMD9L, SAMHD1, SART3, SASH3, SBDS, SCGN, SEC23B, SEC61A1, SEMA3E, SERAC1, SERPING1, SFTPB, SGPL1, SH2D1A, SH3BP2, SH3KBP1, SH3PXD2B, SIRT1, SKIV2L, SLC13A4, SLC26A3, SLC29A3, SLC35C1, SLC37A4, SLC39A4, SLC39A7, SLC46A1, SLC7A4, SLC7A7, SLC9A3, SLCO2A1, SLFN14, SLX4, SMARCAL1, SMARCD2, SNORA31, SNX10, SOCS1, SP110, SPAG1, SPI1, SPINK5, SPPL2A, SRC, SRP19, SRP54, SRP72, SRPRA, STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6, STIM1, STING1, STK36, STK4, STN1, STX11, STXBP2, STXBP3, SYK, TAFAZZIN, TAP1, TAP2, TAPBP, TAZ, TBCE, TBK1, TBX1, TBX21, TBXA2R, TBXAS1 , TCF3, TCIRG1, TCN2, TERC, TERT, TET2, TFRC, TGFB1, TGFBR1, TGFBR2, THBD, THPO, TICAM1, TINF2, TIRAP, TLN1, TLR3, TLR7, TLR8, TMC6, TMC8, TMEM173, TNFAIP3, TNFRSF11A, TNFRSF13B, TNFRSF13C, TNFRSF1A, TNFRSF4, TNFRSF9, TNFSF11, TNFSF12, TNFSF13, TNIP1, TOM1, TOP2B, TP53, TPP2, TRAC, TRADD, TRAF2, TRAF3, TRAF3IP2, TRAP1, TREX1, TRIM22, TRNT1, TRPM7, TSPAN14, TSR2, TTC25, TTC37, TTC7A, TUBA4A, TUBA8, TUBB1, TUBGCP3, TYK2, UBA1, UBE2T, UNC119, UNC13D, UNC93B1, UNG, USB1, USP18, VAV1, VIPAS39, VPREB1, VPS13B, VPS33B, VPS45, VSIG4, VTN, VWF, WAS, WDR1, WIPF1, WRAP53, XIAP, XRCC2, XYLT2, ZAP70, ZBTB24, ZC3HC1, ZFP36, ZMYND10, ZNF34, ZNF341, ZNFX1.
Referenceinterval
Genome Reference Consortium Human Build 38 (hg38).
Måleområde
Ikke defineret
Referencer
OMIM, HGMD, Clinvar, gnomAD og andre relevante databaser over gener involveret i primær immundefekt.
Bemærkninger
Varianter rapporteres jf. HGVS Recommendations for the Description of Sequence Variants: 2016 Update. den Dunnen JT, Dalgleish R, Maglott DR, Hart RK, Greenblatt MS, McGowan-Jordan J, et al. Hum Mutat. 2016. PMID: 26931183
(https://hgvs-nomenclature.org/stable/).
Analysen er ikke akkrediteret.