Bone marrow failure
| Disease . | Genetic defect . | Inheritance . | Gene OMIM . | T cells . | B cells . | Other affected cells . | Associated features . | Major category . | Subcategory . |
|---|---|---|---|---|---|---|---|---|---|
| 1. Bone marrow failure | |||||||||
| Fanconi anemia type A | FANCA | AR | 227650 | Normal to low | Normal to low | HSC | Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage | Bone marrow failure with immune deficiency | Fanconi anemia |
| Fanconi anemia type B | FANCB | XLR | 300514 | ||||||
| Fanconi anemia type C | FANCC | AR | 227645 | ||||||
| Fanconi anemia type D1 | BRCA2 | AR | 605724 | ||||||
| Fanconi anemia type D2 | FANCD2 | AR | 227646 | ||||||
| Fanconi anemia type E | FANCE | AR | 600901 | ||||||
| Fanconi anemia type F | FANCF | AR | 603467 | ||||||
| Fanconi anemia type G | FANCG/XRCC9 | AR | 614082 | ||||||
| Fanconi anemia type I | FANCI | AR | 609053 | ||||||
| Fanconi anemia type J | BRIP1 | AR | 609054 | ||||||
| Fanconi anemia type L | FANCL | AR | 614083 | ||||||
| Fanconi anemia type M | FANCM | AR | 618096 | ||||||
| Fanconi anemia type N | PALB2 | AR | 610832 | ||||||
| Fanconi anemia type O | RAD51C | AR | 613390 | ||||||
| Fanconi anemia type P | SLX4 | AR | 613951 | ||||||
| Fanconi anemia type Q | ERCC4 | AR | 615272 | ||||||
| Fanconi anemia type R | RAD51 | AR | 617244 | ||||||
| Fanconi anemia type S | BRCA1 | AR | 617883 | ||||||
| Fanconi anemia type T | UBE2T | AR | 616435 | ||||||
| Fanconi anemia type U | XRCC2 | AR | 617247 | ||||||
| Fanconi anemia type V | MAD2L2 | AR | 617243 | ||||||
| Fanconi anemia type W | RFWD3 | AR | 617784 | ||||||
| MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, enteropathy) | SAMD9 | AD GOF | 617053 | Not reported | Not reported | HSC, myeloid cells | Intrauterine growth retardation, gonadal abnormalities, adrenal failure, MDS with chromosome 7 aberrations, predisposition to infections, enteropathy, absent spleen | ||
| Ataxia–pancytopenia syndrome | SAMD9L | AD GOF | 611170 | Normal | Low | HSC, myeloid cells | MDS, neurological features | ||
| DKCX1 | DKC1 | XL | 305000 | Normal to low | Normal to low | HSC | Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay | Dyskeratosis congenita | |
| DKCA1 | TERC | AD | 127550 | ||||||
| DKCA2 | TERT | AD/AR | 187270 | ||||||
| DKCA3 | TINF2 | AD | 604319 | ||||||
| DKCA4 | RTEL1 | AD | 616373 | ||||||
| DKCA5 | TINF2 | AD | 268130 | ||||||
| DKCA6 | ACD | AD | 616553 | ||||||
| DKCB1 | NOP10/NOLA3 | AR | 224230 | ||||||
| DKCB2 | NHP2/NOLA2 | AR | 613987 | ||||||
| DKCB3 | WRAP53 | AR | 613988 | ||||||
| DKCB4 | TERT | AR | 613989 | ||||||
| DKCB5 | RTEL1 | AR | 615190 | Low | Nail dystrophy, leukoplakia, bone marrow failure, severe B-cell immunodeficiency, intrauterine growth retardation, growth retardation, microcephaly, cerebellar hypoplasia, and esophageal dysfunction | ||||
| DKCB6 | PARN | AR | 616353 | Normal to low | Developmental delay, microcephaly, and cerebellar hypoplasia | ||||
| DKCB7 | ACD | AR | 616553 | Normal to low | Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay | ||||
| BMFS1 (SRP72-deficiency) | SRP72 | AD | 602122 | NA | NA | Bone marrow failure and congenital nerve deafness | |||
| BMFS2 | ERCC6L2 | AR | 615667 | NA | NA | Bone marrow failure, learning difficulties, microcephaly | |||
| BMFS5 | TP53 | AD | 618165 | NA | Low B | Erythroid hypoplasia, B-cell deficiency | |||
| Coats plus syndrome | STN1 | AR | 613129 | Normal | Normal | Intrauterine growth retardation, premature aging, pancytopenia, hypocellular bone marrow, gastrointestinal hemorrhage due to vascular ectasia, intracranial calcification, abnormal telomeres | |||
| CTC1 | AR | 617053 | Not reported | Not reported | |||||
| MECOM deficiency | MECOM | AD | 616738 | Not reported | B-cell deficiency | Bone marrow failure, thrombocytopenia/pancytopenia, radioulnar synostosis, clinodactyly, cardiac, and renal malformations | |||
| Dyskeratosis congenita, Høyeraal–Hreidarsson syndrome | DCLRE1B | AR | 620133 | Normal to low, reduced CD45RA | B-cell deficiency | Low neutrophils in n:1 | Early-onset hypocellular bone marrow failure, B and NK lymphopenia, developmental anomalies, microcephaly, and/or intrauterine growth retardation | ||
| BMF, macrocytosis, leukemia | DUT | AR | 620044 | NA | NA | HSC, stromal cells | Diabetes, bone marrow failure | BMF | |
| Nijmegen breakage syndrome–like disorder | RAD50 | AR | 613078 | Low T-cell counts, normal T-cell proportions and proliferation | B-cell deficiency | Microcephaly, mental retardation, bird-like face, short stature | Progressive BMF and immunodeficiency | ||
| Disease . | Genetic defect . | Inheritance . | Gene OMIM . | T cells . | B cells . | Other affected cells . | Associated features . | Major category . | Subcategory . |
|---|---|---|---|---|---|---|---|---|---|
| 1. Bone marrow failure | |||||||||
| Fanconi anemia type A | FANCA | AR | 227650 | Normal to low | Normal to low | HSC | Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage | Bone marrow failure with immune deficiency | Fanconi anemia |
| Fanconi anemia type B | FANCB | XLR | 300514 | ||||||
| Fanconi anemia type C | FANCC | AR | 227645 | ||||||
| Fanconi anemia type D1 | BRCA2 | AR | 605724 | ||||||
| Fanconi anemia type D2 | FANCD2 | AR | 227646 | ||||||
| Fanconi anemia type E | FANCE | AR | 600901 | ||||||
| Fanconi anemia type F | FANCF | AR | 603467 | ||||||
| Fanconi anemia type G | FANCG/XRCC9 | AR | 614082 | ||||||
| Fanconi anemia type I | FANCI | AR | 609053 | ||||||
| Fanconi anemia type J | BRIP1 | AR | 609054 | ||||||
| Fanconi anemia type L | FANCL | AR | 614083 | ||||||
| Fanconi anemia type M | FANCM | AR | 618096 | ||||||
| Fanconi anemia type N | PALB2 | AR | 610832 | ||||||
| Fanconi anemia type O | RAD51C | AR | 613390 | ||||||
| Fanconi anemia type P | SLX4 | AR | 613951 | ||||||
| Fanconi anemia type Q | ERCC4 | AR | 615272 | ||||||
| Fanconi anemia type R | RAD51 | AR | 617244 | ||||||
| Fanconi anemia type S | BRCA1 | AR | 617883 | ||||||
| Fanconi anemia type T | UBE2T | AR | 616435 | ||||||
| Fanconi anemia type U | XRCC2 | AR | 617247 | ||||||
| Fanconi anemia type V | MAD2L2 | AR | 617243 | ||||||
| Fanconi anemia type W | RFWD3 | AR | 617784 | ||||||
| MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, enteropathy) | SAMD9 | AD GOF | 617053 | Not reported | Not reported | HSC, myeloid cells | Intrauterine growth retardation, gonadal abnormalities, adrenal failure, MDS with chromosome 7 aberrations, predisposition to infections, enteropathy, absent spleen | ||
| Ataxia–pancytopenia syndrome | SAMD9L | AD GOF | 611170 | Normal | Low | HSC, myeloid cells | MDS, neurological features | ||
| DKCX1 | DKC1 | XL | 305000 | Normal to low | Normal to low | HSC | Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay | Dyskeratosis congenita | |
| DKCA1 | TERC | AD | 127550 | ||||||
| DKCA2 | TERT | AD/AR | 187270 | ||||||
| DKCA3 | TINF2 | AD | 604319 | ||||||
| DKCA4 | RTEL1 | AD | 616373 | ||||||
| DKCA5 | TINF2 | AD | 268130 | ||||||
| DKCA6 | ACD | AD | 616553 | ||||||
| DKCB1 | NOP10/NOLA3 | AR | 224230 | ||||||
| DKCB2 | NHP2/NOLA2 | AR | 613987 | ||||||
| DKCB3 | WRAP53 | AR | 613988 | ||||||
| DKCB4 | TERT | AR | 613989 | ||||||
| DKCB5 | RTEL1 | AR | 615190 | Low | Nail dystrophy, leukoplakia, bone marrow failure, severe B-cell immunodeficiency, intrauterine growth retardation, growth retardation, microcephaly, cerebellar hypoplasia, and esophageal dysfunction | ||||
| DKCB6 | PARN | AR | 616353 | Normal to low | Developmental delay, microcephaly, and cerebellar hypoplasia | ||||
| DKCB7 | ACD | AR | 616553 | Normal to low | Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay | ||||
| BMFS1 (SRP72-deficiency) | SRP72 | AD | 602122 | NA | NA | Bone marrow failure and congenital nerve deafness | |||
| BMFS2 | ERCC6L2 | AR | 615667 | NA | NA | Bone marrow failure, learning difficulties, microcephaly | |||
| BMFS5 | TP53 | AD | 618165 | NA | Low B | Erythroid hypoplasia, B-cell deficiency | |||
| Coats plus syndrome | STN1 | AR | 613129 | Normal | Normal | Intrauterine growth retardation, premature aging, pancytopenia, hypocellular bone marrow, gastrointestinal hemorrhage due to vascular ectasia, intracranial calcification, abnormal telomeres | |||
| CTC1 | AR | 617053 | Not reported | Not reported | |||||
| MECOM deficiency | MECOM | AD | 616738 | Not reported | B-cell deficiency | Bone marrow failure, thrombocytopenia/pancytopenia, radioulnar synostosis, clinodactyly, cardiac, and renal malformations | |||
| Dyskeratosis congenita, Høyeraal–Hreidarsson syndrome | DCLRE1B | AR | 620133 | Normal to low, reduced CD45RA | B-cell deficiency | Low neutrophils in n:1 | Early-onset hypocellular bone marrow failure, B and NK lymphopenia, developmental anomalies, microcephaly, and/or intrauterine growth retardation | ||
| BMF, macrocytosis, leukemia | DUT | AR | 620044 | NA | NA | HSC, stromal cells | Diabetes, bone marrow failure | BMF | |
| Nijmegen breakage syndrome–like disorder | RAD50 | AR | 613078 | Low T-cell counts, normal T-cell proportions and proliferation | B-cell deficiency | Microcephaly, mental retardation, bird-like face, short stature | Progressive BMF and immunodeficiency | ||
HSC, hematopoietic stem cell; NK, natural killer; CNS, central nervous system; GI, gastrointestinal, MDS, myelodysplastic syndrome; DKCX: X-linked dyskeratosis congenital; DKCA, autosomal dominant dyskeratosis congenita; DKCB, autosomal recessive dyskeratosis congenita; BMFS, bone marrow failure syndrome.
Total number of mutant genes in Table 9: 47.
New IEIs: 3, DCLRE1B (Apollo), DUT, and RAD50 (99, 121, 122).