IEIs affecting central B cell development
| Disease . | Genetic defect . | Inheritance . | Effect . | OMIM . | Stage affected . | Reference . |
|---|---|---|---|---|---|---|
| AIOLOS deficiency | IKZF3 | AD | DN | 606221 | Small pre-B/immature B | (19) |
| E47 transcription factor deficiency | TCF3 | AD | DN | 147141 | CLP | (20) |
| E47 transcription factor deficiency | TCF3 | AR | LOF | 147141 | CLP | (21) |
| FLT3L deficiency | FLT3LG | AR | LOF | 600007 | CLP/pro-B | (22) |
| Ikaros deficiency | IKZF1 | AD | DN | - | CLP | (23) |
| IKAROS haploinsufficiency | IKZF1 | AD | LOF (HI) | 616873 | CLP | (24) |
| PAX5 deficiency | PAX5 | AR | LOF | - | Late pro-B/large pre-B | (25) |
| Pu.1 deficiency | SPI1 | AD | LOF (HI) | 165170 | Late pro-B/large pre-B | (26) |
| Ataxia-telangiectasia | ATM | AR | LOF | 607585 | Early pro-B | (27) |
| Cernunnos/XLF deficiency | NHEJ1 | AR | LOF | 611290 | Early pro-B | (28) |
| DCLRE1C (Artemis) deficiency | DCLRE1C | AR | LOF | 605988 | Early pro-B | (29) |
| DNA ligase IV deficiency | LIG4 | AR | LOF | 601837 | Early pro-B | (30) |
| DNA PKcs deficiency | PRKDC | AR | LOF | 600899 | Early pro-B | (31) |
| Nijmegen breakage syndrome | NBN | AR | LOF | 602667 | Large pre-B/small pre-B | (32) |
| NUDCD3 deficiency | NUDCD3 | AR | LOF | - | Early pro-B | (33) |
| PSMB10-associated Omenn syndrome | PSMB10 | AD | DN* | 176847 | Early pro-B | (34) |
| RAD50 deficiency | RAD50 | AR | LOF | 613078 | Late pro-B/large pre-B | (35) |
| RAG1 deficiency | RAG1 | AR | LOF | 179615 | Early pro-B | (36) |
| RAG2 deficiency | RAG2 | AR | LOF | 179616 | Early pro-B | (36) |
| Tricho-hepato-enteric syndrome due to SKIV2L mutations | SKIV2L | AR | LOF | 614602 | Early pro-B | (37) |
| BLNK deficiency | BLNK | AR | LOF | 604515 | Late pro-B/large pre-B | (38) |
| BTK deficiency, X-linked agammaglobulinemia | BTK | XL | LOF | 300300 | Late pro-B/large pre-B | (39) |
| Igα deficiency | CD79A | AR | LOF | 112205 | Late pro-B | (40) |
| Igβ deficiency | CD79B | AR | LOF | 147245 | Late pro-B | (41) |
| λ5 deficiency | IGLL1 | AR | LOF | 146770 | Late pro-B | (42) |
| μ heavy chain deficiency | IGHM | AR | LOF | 147020 | Late pro-B | (43) |
| PIK3CD mutation (GOF) APDS1 | PIK3CD | AD | GOF | 602839 | Late pro-B/large pre-B | (44) |
| PIK3R1 deficiency | PIK3R1 | AR | LOF | 171833 | N/A | (45) |
| PIK3R1 deficiency (LOF) APDS2 | PIK3R1 | AD | LOF | 171833 | Late pro-B/large pre-B | (44) |
| SLC39A7 (ZIP7) deficiency | SLC39A7 | AR | LOF | 601416 | Late pro-B/large pre-B | (46) |
| Hoffman syndrome/TOP2B deficiency | TOP2B | AD | DN | 126431 | CLP/pro-B | (47, 48) |
| POLE1 (Polymerase ε subunit 1) deficiency (IMAGe-1) | POLE1 | AR | LOF | 174762 | N/A | (49) |
| POLE2 (Polymerase ε subunit 2) deficiency | POLE2 | AR | LOF | 602670 | Small pre-B/immature B | (50) |
| Polymerase δ 1 deficiency | POLD1 | AR | LOF | 174761 | Small pre-B/immature B | (51) |
| FNIP1 deficiency | FNIP1 | AR | LOF | 610594 | Large pre-B | (52) |
| TRNT1 deficiency | TRNT1 | AR | LOF | 612907 | Large pre-B | (53) |
| Disease . | Genetic defect . | Inheritance . | Effect . | OMIM . | Stage affected . | Reference . |
|---|---|---|---|---|---|---|
| AIOLOS deficiency | IKZF3 | AD | DN | 606221 | Small pre-B/immature B | (19) |
| E47 transcription factor deficiency | TCF3 | AD | DN | 147141 | CLP | (20) |
| E47 transcription factor deficiency | TCF3 | AR | LOF | 147141 | CLP | (21) |
| FLT3L deficiency | FLT3LG | AR | LOF | 600007 | CLP/pro-B | (22) |
| Ikaros deficiency | IKZF1 | AD | DN | - | CLP | (23) |
| IKAROS haploinsufficiency | IKZF1 | AD | LOF (HI) | 616873 | CLP | (24) |
| PAX5 deficiency | PAX5 | AR | LOF | - | Late pro-B/large pre-B | (25) |
| Pu.1 deficiency | SPI1 | AD | LOF (HI) | 165170 | Late pro-B/large pre-B | (26) |
| Ataxia-telangiectasia | ATM | AR | LOF | 607585 | Early pro-B | (27) |
| Cernunnos/XLF deficiency | NHEJ1 | AR | LOF | 611290 | Early pro-B | (28) |
| DCLRE1C (Artemis) deficiency | DCLRE1C | AR | LOF | 605988 | Early pro-B | (29) |
| DNA ligase IV deficiency | LIG4 | AR | LOF | 601837 | Early pro-B | (30) |
| DNA PKcs deficiency | PRKDC | AR | LOF | 600899 | Early pro-B | (31) |
| Nijmegen breakage syndrome | NBN | AR | LOF | 602667 | Large pre-B/small pre-B | (32) |
| NUDCD3 deficiency | NUDCD3 | AR | LOF | - | Early pro-B | (33) |
| PSMB10-associated Omenn syndrome | PSMB10 | AD | DN* | 176847 | Early pro-B | (34) |
| RAD50 deficiency | RAD50 | AR | LOF | 613078 | Late pro-B/large pre-B | (35) |
| RAG1 deficiency | RAG1 | AR | LOF | 179615 | Early pro-B | (36) |
| RAG2 deficiency | RAG2 | AR | LOF | 179616 | Early pro-B | (36) |
| Tricho-hepato-enteric syndrome due to SKIV2L mutations | SKIV2L | AR | LOF | 614602 | Early pro-B | (37) |
| BLNK deficiency | BLNK | AR | LOF | 604515 | Late pro-B/large pre-B | (38) |
| BTK deficiency, X-linked agammaglobulinemia | BTK | XL | LOF | 300300 | Late pro-B/large pre-B | (39) |
| Igα deficiency | CD79A | AR | LOF | 112205 | Late pro-B | (40) |
| Igβ deficiency | CD79B | AR | LOF | 147245 | Late pro-B | (41) |
| λ5 deficiency | IGLL1 | AR | LOF | 146770 | Late pro-B | (42) |
| μ heavy chain deficiency | IGHM | AR | LOF | 147020 | Late pro-B | (43) |
| PIK3CD mutation (GOF) APDS1 | PIK3CD | AD | GOF | 602839 | Late pro-B/large pre-B | (44) |
| PIK3R1 deficiency | PIK3R1 | AR | LOF | 171833 | N/A | (45) |
| PIK3R1 deficiency (LOF) APDS2 | PIK3R1 | AD | LOF | 171833 | Late pro-B/large pre-B | (44) |
| SLC39A7 (ZIP7) deficiency | SLC39A7 | AR | LOF | 601416 | Late pro-B/large pre-B | (46) |
| Hoffman syndrome/TOP2B deficiency | TOP2B | AD | DN | 126431 | CLP/pro-B | (47, 48) |
| POLE1 (Polymerase ε subunit 1) deficiency (IMAGe-1) | POLE1 | AR | LOF | 174762 | N/A | (49) |
| POLE2 (Polymerase ε subunit 2) deficiency | POLE2 | AR | LOF | 602670 | Small pre-B/immature B | (50) |
| Polymerase δ 1 deficiency | POLD1 | AR | LOF | 174761 | Small pre-B/immature B | (51) |
| FNIP1 deficiency | FNIP1 | AR | LOF | 610594 | Large pre-B | (52) |
| TRNT1 deficiency | TRNT1 | AR | LOF | 612907 | Large pre-B | (53) |
AR: autosomal recessive; DN: dominant negative; HI: haploinsufficient; XL: X-linked.