IBMFS: mechanisms and mutations
| Disorder . | Pathophysiology . | Genes . |
|---|---|---|
| Pancytopenia (trilineage cytopenias) | ||
| Fanconi anemia | Faulty DNA crosslink repair | FANCA, FANCB, FANCC, FANCD1 (BRCA2), FANCD2, FANCE, FANCF, FANCG (XRCC9), FANCI, FANCJ (BRIP1), FANCL, FANCM, FANCN (PALB2), FANCO (RAD51C), FANCP (SLX4), FANCQ (ERCC4), FANCR (RAD51), FANCS (BRCA1), FANCT (UBE2T), FANCU (XRCC2), FANCV (MAD2L2) |
| Dyskeratosis congenita | Defective telomere maintenance | DKC1, TINF2, TERC, TERT, RTEL1, CTC1, NOP10 (NOLA3), NHP2 (NOLA2), PARN, ACD, WRAP53 (TCAB1) |
| Single-lineage cytopenias | ||
| Red cells | ||
| DBA | Abnormal ribosome biosynthesis/rRNA processing | RPS7, RPS10, RPS15A, RPS17, RPS19, RPS20, RPS24, RPS26, RPS27, RPS28, RPS29, RPS31, RPL5, RPL11, RPL15, RPL18, RPL26, RPL27, RPL35, RPL35A, TSR2 |
| Defective transcription | GATA1 | |
| Cytokine dysfunction | EPO (erythropoietin) | |
| Neutrophils | ||
| SCN | Misfolded protein response | ELANE |
| Cytokine receptor dysfunction | CSF3R (GCSF receptor) | |
| Kostmann syndrome | Proapoptosis | HAX1 |
| Shwachman-Diamond syndrome | Ribosome assembly | SBDS, DNAJC21 |
| Others | Varied | (GFI1, WAS, G6PC3, CSF3R, CXCR4, etc) |
| Megakaryocytes/platelets | ||
| AT | Cytokine | THPO (thrombopoietin) |
| Cytokine receptor dysfunction | c-mpl (thrombopoietin receptor) | |
| TAR syndrome | Exon-junction complex defect (mRNA-processing defect) | RBM8A |
| Disorder . | Pathophysiology . | Genes . |
|---|---|---|
| Pancytopenia (trilineage cytopenias) | ||
| Fanconi anemia | Faulty DNA crosslink repair | FANCA, FANCB, FANCC, FANCD1 (BRCA2), FANCD2, FANCE, FANCF, FANCG (XRCC9), FANCI, FANCJ (BRIP1), FANCL, FANCM, FANCN (PALB2), FANCO (RAD51C), FANCP (SLX4), FANCQ (ERCC4), FANCR (RAD51), FANCS (BRCA1), FANCT (UBE2T), FANCU (XRCC2), FANCV (MAD2L2) |
| Dyskeratosis congenita | Defective telomere maintenance | DKC1, TINF2, TERC, TERT, RTEL1, CTC1, NOP10 (NOLA3), NHP2 (NOLA2), PARN, ACD, WRAP53 (TCAB1) |
| Single-lineage cytopenias | ||
| Red cells | ||
| DBA | Abnormal ribosome biosynthesis/rRNA processing | RPS7, RPS10, RPS15A, RPS17, RPS19, RPS20, RPS24, RPS26, RPS27, RPS28, RPS29, RPS31, RPL5, RPL11, RPL15, RPL18, RPL26, RPL27, RPL35, RPL35A, TSR2 |
| Defective transcription | GATA1 | |
| Cytokine dysfunction | EPO (erythropoietin) | |
| Neutrophils | ||
| SCN | Misfolded protein response | ELANE |
| Cytokine receptor dysfunction | CSF3R (GCSF receptor) | |
| Kostmann syndrome | Proapoptosis | HAX1 |
| Shwachman-Diamond syndrome | Ribosome assembly | SBDS, DNAJC21 |
| Others | Varied | (GFI1, WAS, G6PC3, CSF3R, CXCR4, etc) |
| Megakaryocytes/platelets | ||
| AT | Cytokine | THPO (thrombopoietin) |
| Cytokine receptor dysfunction | c-mpl (thrombopoietin receptor) | |
| TAR syndrome | Exon-junction complex defect (mRNA-processing defect) | RBM8A |
mRNA, messenger RNA; rRNA, ribosomal RNA.