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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