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Table 1 Classification of SCID.

From: Genetics of SCID

Prevalent mechanisms/Disease T/B/NK Gene Locus Heredity Protein §§ Nonimmunological manifestations
Impaired cytokine-mediated signaling       
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  
IL-7Rα chain defect T-B+NK+ IL7RA 5p13 AR IL-7 and TSLP receptor α chain  
Defects of the pre-T cell receptor       
Defects in V(D)J recombination       
RAG1 defect T-B-NK+ RAG1 11p13 AR RAG1  
RAG2 defect T-B-NK+ RAG2 11p13 AR RAG2  
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       
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)  
ZAP-70 defect T+B+NK+ ZAP70 2q11.2 AR ZAP-70  
  CD4+ CD8-      
p56lck defect T-B+NK+ LCK 1p35.1 AR p56lck  
Increased lymphocyte apoptosis       
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       
Nude/SCID Syndrome T-B+NK+ WHN 17q11.2 AR FOXN1 alopecia; embryonic neural tube defects
Complete DiGeorge Anomaly       
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+      congenital heart disease, gut and kidney malformations, neural tube defects, sacral agenesis, holoprosencephaly, neonatal hypoglycemia
Impaired calcium flux       
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       
Coronin-1A defect T-B+NK+ CORO1A 16p11.2 AR Coronin-1A  
MHC Class II defect T+B+NK+ CIITA 16p13.13 AR CIITA  
  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