From: Genetics of SCID
Prevalent mechanisms/Disease | T/B/NK | Gene | Locus | Heredity | Protein §§ | Nonimmunological manifestations |
---|---|---|---|---|---|---|
Impaired cytokine-mediated signaling | Â | Â | Â | Â | Â | Â |
Common γ chain defect | T-B+NK- | IL2RG | Xq13.1 | XL | Common γ chain |  |
JAK3 defect | T-B+NK- | JAK3 | 19p13.1 | AR | Janus kinase 3 | Â |
IL-7Rα chain defect | T-B+NK+ | IL7RA | 5p13 | AR | IL-7 and TSLP receptor α chain |  |
Defects of the pre-T cell receptor | Â | Â | Â | Â | Â | Â |
Defects in V(D)J recombination | Â | Â | Â | Â | Â | Â |
RAG1 defect | T-B-NK+ | RAG1 | 11p13 | AR | RAG1 | Â |
RAG2 defect | T-B-NK+ | RAG2 | 11p13 | AR | RAG2 | Â |
Artemis defect | T-B-NK+ | DCLRE1C | 10p13 | AR | Artemis | radiosensitivity |
DNA-PKcs defect | T-B-NK+ | PRKDC | 8q11.21 | AR | DNA-PKcs | radiosensitivity |
DNA ligasi IV defect | T-B-NK+ | LIG4 | 13q33.3 | AR | DNA ligasi IV | radiosensitivity, dysmorphic facies, microcephaly, growth retardation, psychomotor delay |
Cernunnos/XLF defect | T-B-NK+ | NHEJ1 | 2q35 | AR | Cernunnos/XLF | radiosensitivity, dysmorphic facies, microcephaly, growth retardation, psychomotor delay |
Impaired signaling through the pre-T cell receptor | Â | Â | Â | Â | Â | Â |
CD3δ defect | T-B+NK+ | CD3D | 11q23 | AR | CD3δ |  |
CD3ε defect | T-B+NK+ | CD3E | 11q23 | AR | CD3ε |  |
CD3ζ defect | T-B+NK+ | CD3Z | 1q24.2 | AR | CD3ζ |  |
CD3γ defect | T-B+NK+ | CD3G | 11q23 | AR | CD3γ |  |
CD45 | T-B+NK-/+ | PTPRC | 1q31.3 | AR | CD45 (LCA) | Â |
ZAP-70 defect | T+B+NK+ | ZAP70 | 2q11.2 | AR | ZAP-70 | Â |
 | CD4+ CD8- |  |  |  |  |  |
p56lck defect | T-B+NK+ | LCK | 1p35.1 | AR | p56lck | Â |
Increased lymphocyte apoptosis | Â | Â | Â | Â | Â | Â |
Reticular dysgenesis | T-B-NK- | AK2 | 1p34 | AR | Adenylate kinase 2 | aleukocytosis, sensorineural deafness |
ADA-SCID | T-B-NK- | ADA | 20q13.11 | AR | Adenosine deaminase | costochondral and skeletal alterations, neonatal hepatitis, sensorineural deafness, neurological problems |
PNP-SCID | T-B-NK- | PNP | 14q11.2 | AR | Purine nucleoside phosphorylase | neurological problems |
Defects in thymus embryogenesis | Â | Â | Â | Â | Â | Â |
Nude/SCID Syndrome | T-B+NK+ | WHN | 17q11.2 | AR | FOXN1 | alopecia; embryonic neural tube defects |
Complete DiGeorge Anomaly | Â | Â | Â | Â | Â | Â |
DiGeorge Syndrome (del22q11.2) | T-B+NK+ | > 35 genes | 22q11.2 | AD | TBX1, and others | dysmorphic facies, congenital heart disease and other malformations, neonatal hypocalcemia by absence of parathyroid glands |
CHARGE | T-B+NK+ | CHD7 | 8q12.1 | AD | CHD-7 | CHARGE association (coloboma, heart defects, atresia choanae, retardated growth and development, genital hypoplasia, ear anomalies/deafness) |
Diabetic mother embryopathy | T-B+NK+ | Â | Â | Â | Â | congenital heart disease, gut and kidney malformations, neural tube defects, sacral agenesis, holoprosencephaly, neonatal hypoglycemia |
Impaired calcium flux | Â | Â | Â | Â | Â | Â |
ORAI1 defect | T+B+NK+ | ORAI1 | 12q24 | AR | ORAI1 | myopathy, ectodermal dysplasia |
STIM1 defect | T+B+NK+ | STIM1 | 11p15.5 | AR | STIM1 | myopathy, ectodermal dysplasia |
Other mechanisms | Â | Â | Â | Â | Â | Â |
Coronin-1A defect | T-B+NK+ | CORO1A | 16p11.2 | AR | Coronin-1A | Â |
MHC Class II defect | T+B+NK+ | CIITA | 16p13.13 | AR | CIITA | Â |
 | CD4- CD8+ | RFXANK | 19p13.11 | AR | RFXANK |  |
 |  | RFX5 | 1q21.2 | AR | RFX5 |  |
 |  | RFXAP | 13q13.3 | AR | RFXAP |  |
CHH (Cartilage hair hypoplasia) | T-B+NK+ | RMRP | 9p13.3 | AR | §§ RNA of RNase MRP complex | short-limbed dwarfism, light-colored hypoplastic hair |
Hoyeraal-Hreidarsson Syndrome (HHS) | T+B-NK- | DKC1 | Xq28 | XL | Dyskerin | cerebellar hypoplasia, microcephaly, growth retardation, bone marrow failure, hypoplastic hair |
 |  | TERT | 5p15.33 | AR | TERT |  |
 |  | TINF2 | 14q12 | AD | TIN2 |  |
 |  | DCLRE1B | 1p13.2 | AD | Apollo |  |
Hereditary folate malabsorption (HFM) | T+B+NK+ | SLC46A1 | 17q11.2 | AR | PCFT | megaloblastic anemia, seizures, risk of severe neurodevelopmental defects |