MCID: SVR010
MIFTS: 38

Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation

Categories: Genetic diseases, Rare diseases, Blood diseases, Immune diseases

Aliases & Classifications for Severe Combined Immunodeficiency with Sensitivity to Ionizing...

MalaCards integrated aliases for Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation:

Name: Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation 57 12 53 75 29 13 6 40 73
Severe Combined Immunodeficiency, Athabascan Type 57 12 59
Scid, Autosomal Recessive, T Cell-Negative, B Cell-Negative, Nk Cell-Positive, with Sensitivity to Ionizing Radiation 57 53
Severe Combined Immunodeficiency Due to Artemis Deficiency 12 59
Severe Combined Immunodeficiency Due to Dclre1c Deficiency 12 59
Severe Combined Immunodeficiency, Athabaskan Type 12 59
Scid Due to Artemis Deficiency 12 59
Scid Due to Dclre1c Deficiency 12 59
Scid, Athabascan Type 12 59
Scid, Athabaskan Type 12 59
Rs-Scid 57 53
Severe Combined Immunodeficiency Autosomal Recessive T-Cell-Negative/b-Cell-Negative/nk-Cell-Positive with Sensitivity to Ionizing Radiation 75
Severe Combined Immunodeficiency, Athabascan-Type 6
Severe Combined Immunodeficiency, Athabaskan-Type 73
Severe Combined Immunodeficiency Athabaskan Type 75
Athabascan Scid 75
Rsscid 75
Scida 75

Characteristics:

Orphanet epidemiological data:

59
severe combined immunodeficiency due to dclre1c deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype
onset in early childhood
some patients may present with isolated antibody deficiency


HPO:

32
severe combined immunodeficiency with sensitivity to ionizing radiation:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare immunological diseases


External Ids:

OMIM 57 602450
Disease Ontology 12 DOID:0090012
ICD10 33 D81.1
Orphanet 59 ORPHA275
ICD10 via Orphanet 34 D81.1
UMLS via Orphanet 74 C1865372
MeSH 44 D016511

Summaries for Severe Combined Immunodeficiency with Sensitivity to Ionizing...

UniProtKB/Swiss-Prot : 75 Severe combined immunodeficiency Athabaskan type: A variety of SCID with sensitivity to ionizing radiation. A founder mutation has been detected in Athabascan-speaking native Americans, being inherited as an autosomal recessive trait. Affected individuals exhibit clinical symptoms and defects in DNA repair comparable to those seen in RS-SCID. Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive with sensitivity to ionizing radiation: A form of severe combined immunodeficiency, a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. Individuals affected by RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J recombination. A subset of cells from such patients show increased radiosensitivity.

MalaCards based summary : Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation, also known as severe combined immunodeficiency, athabascan type, is related to lig4 syndrome and seckel syndrome, and has symptoms including diarrhea An important gene associated with Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation is DCLRE1C (DNA Cross-Link Repair 1C), and among its related pathways/superpathways are DNA Double-Strand Break Repair and DNA Damage. Affiliated tissues include b cells, t cells and nk cells, and related phenotypes are failure to thrive and recurrent upper respiratory tract infections

Disease Ontology : 12 A severe combined immunodeficiency characterized by being T cell-negative, B cell-negative and natural killer cell-positive with sensitivity to ionizing radiation and that has material basis in mutation in the DCLRE1C gene on chromosome 10p13.

Description from OMIM: 602450

Related Diseases for Severe Combined Immunodeficiency with Sensitivity to Ionizing...

Diseases related to Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 lig4 syndrome 28.0 DCLRE1C LIG4 NHEJ1
2 seckel syndrome 9.9
3 artemis deficiency 9.1 DCLRE1C LIG4
4 omenn syndrome 8.9 DCLRE1C LIG4
5 combined immunodeficiency, x-linked 8.7 DCLRE1C LIG4 NHEJ1
6 severe combined immunodeficiency 8.6 DCLRE1C LIG4 NHEJ1

Graphical network of the top 20 diseases related to Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation:



Diseases related to Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation

Symptoms & Phenotypes for Severe Combined Immunodeficiency with Sensitivity to Ionizing...

Symptoms via clinical synopsis from OMIM:

57
Growth Other:
failure to thrive

Abdomen Gastrointestinal:
diarrhea

Respiratory Lung:
pneumonia

Immunology:
hypogammaglobulinemia
decreased numbers of b cells
absent thymus
small lymph nodes
reduced/absent cd3+ t cells
more
Genitourinary External Genitalia Male:
genital ulcers

Respiratory Airways:
recurrent upper respiratory tract infections

Head And Neck Ears:
otitis media

Respiratory Nasopharynx:
absent tonsils

Head And Neck Mouth:
oral ulcers

Genitourinary External Genitalia Female:
genital ulcers


Clinical features from OMIM:

602450

Human phenotypes related to Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation:

32 (show all 12)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 recurrent upper respiratory tract infections 32 HP:0002788
3 diarrhea 32 HP:0002014
4 otitis media 32 HP:0000388
5 pneumonia 32 HP:0002090
6 oral ulcer 32 HP:0000155
7 severe combined immunodeficiency 32 HP:0004430
8 panhypogammaglobulinemia 32 HP:0003139
9 aplasia of the thymus 32 HP:0005359
10 absent tonsils 32 HP:0030813
11 genital ulcers 32 HP:0003249
12 lymph node hypoplasia 32 HP:0002732

UMLS symptoms related to Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation:


diarrhea

GenomeRNAi Phenotypes related to Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 9.56 LIG4
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-145 9.56 DCLRE1C
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-204 9.56 DCLRE1C
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 9.56 LIG4 DCLRE1C
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-26 9.56 DCLRE1C
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 9.56 LIG4
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-87 9.56 DCLRE1C
8 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-3 8.8 DCLRE1C LIG4 NHEJ1

MGI Mouse Phenotypes related to Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 8.8 DCLRE1C LIG4 NHEJ1

Drugs & Therapeutics for Severe Combined Immunodeficiency with Sensitivity to Ionizing...

Search Clinical Trials , NIH Clinical Center for Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation

Genetic Tests for Severe Combined Immunodeficiency with Sensitivity to Ionizing...

Genetic tests related to Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation:

# Genetic test Affiliating Genes
1 Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation 29 DCLRE1C

Anatomical Context for Severe Combined Immunodeficiency with Sensitivity to Ionizing...

MalaCards organs/tissues related to Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation:

41
B Cells, T Cells, Nk Cells, Lymph Node, Thymus, Tonsil

Publications for Severe Combined Immunodeficiency with Sensitivity to Ionizing...

Variations for Severe Combined Immunodeficiency with Sensitivity to Ionizing...

UniProtKB/Swiss-Prot genetic disease variations for Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation:

75
# Symbol AA change Variation ID SNP ID
1 DCLRE1C p.Gly118Val VAR_023078
2 DCLRE1C p.Gly135Glu VAR_023079

ClinVar genetic disease variations for Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation:

6
(show top 50) (show all 183)
# Gene Variation Type Significance SNP ID Assembly Location
1 DCLRE1C NM_001033855.2(DCLRE1C): c.241C> T (p.Arg81Ter) single nucleotide variant Pathogenic rs121908156 GRCh37 Chromosome 10, 14987109: 14987109
2 DCLRE1C NM_001033855.2(DCLRE1C): c.241C> T (p.Arg81Ter) single nucleotide variant Pathogenic rs121908156 GRCh38 Chromosome 10, 14945110: 14945110
3 DCLRE1C DCLRE1C, EX1-4DEL deletion Pathogenic
4 DCLRE1C DCLRE1C, EX5-6DEL deletion Pathogenic
5 DCLRE1C DCLRE1C, IVS11DS, G-C, +1 single nucleotide variant Pathogenic
6 DCLRE1C DCLRE1C, IVS10DS, G-A, +1 single nucleotide variant Pathogenic
7 DCLRE1C DCLRE1C, IVS5DS, G-T, +1 single nucleotide variant Pathogenic
8 DCLRE1C NM_022487.3(DCLRE1C): c.435delG (p.Ala146Glnfs) deletion Pathogenic rs786205074 GRCh37 Chromosome 10, 14974853: 14974853
9 DCLRE1C NM_022487.3(DCLRE1C): c.435delG (p.Ala146Glnfs) deletion Pathogenic rs786205074 GRCh38 Chromosome 10, 14932854: 14932854
10 DCLRE1C DCLRE1C, EX5-8DEL deletion Pathogenic
11 DCLRE1C NM_001033855.2(DCLRE1C): c.597C> A (p.Tyr199Ter) single nucleotide variant Pathogenic rs121908157 GRCh37 Chromosome 10, 14976460: 14976460
12 DCLRE1C NM_001033855.2(DCLRE1C): c.597C> A (p.Tyr199Ter) single nucleotide variant Pathogenic rs121908157 GRCh38 Chromosome 10, 14934461: 14934461
13 DCLRE1C NM_001033855.2(DCLRE1C): c.1346_1352delTTGTAGA (p.Asp451Lysfs) deletion Pathogenic rs786200884 GRCh37 Chromosome 10, 14951134: 14951140
14 DCLRE1C NM_001033855.2(DCLRE1C): c.1346_1352delTTGTAGA (p.Asp451Lysfs) deletion Pathogenic rs786200884 GRCh38 Chromosome 10, 14909135: 14909141
15 LIG4 NM_002312.3(LIG4): c.8C> T (p.Ala3Val) single nucleotide variant protective rs1805389 GRCh37 Chromosome 13, 108863609: 108863609
16 LIG4 NM_002312.3(LIG4): c.8C> T (p.Ala3Val) single nucleotide variant protective rs1805389 GRCh38 Chromosome 13, 108211261: 108211261
17 DCLRE1C NM_001033855.2(DCLRE1C): c.2001A> G (p.Leu667=) single nucleotide variant Conflicting interpretations of pathogenicity rs61749163 GRCh37 Chromosome 10, 14950485: 14950485
18 DCLRE1C NM_001033855.2(DCLRE1C): c.2001A> G (p.Leu667=) single nucleotide variant Conflicting interpretations of pathogenicity rs61749163 GRCh38 Chromosome 10, 14908486: 14908486
19 LIG4 NM_002312.3(LIG4): c.513T> C (p.Leu171=) single nucleotide variant Conflicting interpretations of pathogenicity rs3093764 GRCh37 Chromosome 13, 108863104: 108863104
20 LIG4 NM_002312.3(LIG4): c.513T> C (p.Leu171=) single nucleotide variant Conflicting interpretations of pathogenicity rs3093764 GRCh38 Chromosome 13, 108210756: 108210756
21 DCLRE1C NM_001033855.2(DCLRE1C): c.1669_1670insA (p.Thr557Asnfs) insertion Pathogenic rs886037924 GRCh38 Chromosome 10, 14908818: 14908818
22 DCLRE1C NM_001033855.2(DCLRE1C): c.1669_1670insA (p.Thr557Asnfs) insertion Pathogenic rs886037924 GRCh37 Chromosome 10, 14950817: 14950817
23 DCLRE1C NM_001033855.2(DCLRE1C): c.194C> T (p.Thr65Ile) single nucleotide variant Pathogenic rs886037925 GRCh37 Chromosome 10, 14987156: 14987156
24 DCLRE1C NM_001033855.2(DCLRE1C): c.194C> T (p.Thr65Ile) single nucleotide variant Pathogenic rs886037925 GRCh38 Chromosome 10, 14945157: 14945157
25 DCLRE1C NM_001033855.2(DCLRE1C): c.1284A> C (p.Lys428Asn) single nucleotide variant Likely benign rs113870881 GRCh37 Chromosome 10, 14951202: 14951202
26 DCLRE1C NM_001033855.2(DCLRE1C): c.1284A> C (p.Lys428Asn) single nucleotide variant Likely benign rs113870881 GRCh38 Chromosome 10, 14909203: 14909203
27 LIG4 NM_002312.3(LIG4): c.*1035G> A single nucleotide variant Likely benign rs10131 GRCh38 Chromosome 13, 108207498: 108207498
28 LIG4 NM_002312.3(LIG4): c.*1035G> A single nucleotide variant Likely benign rs10131 GRCh37 Chromosome 13, 108859846: 108859846
29 LIG4 NM_002312.3(LIG4): c.*855_*856insTTTT insertion Likely benign rs146506306 GRCh38 Chromosome 13, 108207677: 108207678
30 LIG4 NM_002312.3(LIG4): c.*855_*856insTTTT insertion Likely benign rs146506306 GRCh37 Chromosome 13, 108860025: 108860026
31 LIG4 NM_002312.3(LIG4): c.*599_*602delCTTA deletion Likely benign rs3093770 GRCh38 Chromosome 13, 108207931: 108207934
32 LIG4 NM_002312.3(LIG4): c.*599_*602delCTTA deletion Likely benign rs3093770 GRCh37 Chromosome 13, 108860279: 108860282
33 LIG4 NM_002312.3(LIG4): c.*562_*563insAAT insertion Likely benign rs112171260 GRCh38 Chromosome 13, 108207970: 108207971
34 LIG4 NM_002312.3(LIG4): c.*562_*563insAAT insertion Likely benign rs112171260 GRCh37 Chromosome 13, 108860318: 108860319
35 LIG4 NM_002312.3(LIG4): c.*486A> G single nucleotide variant Uncertain significance rs543340651 GRCh37 Chromosome 13, 108860395: 108860395
36 LIG4 NM_002312.3(LIG4): c.*486A> G single nucleotide variant Uncertain significance rs543340651 GRCh38 Chromosome 13, 108208047: 108208047
37 LIG4 NM_002312.3(LIG4): c.*352A> C single nucleotide variant Uncertain significance rs886049944 GRCh38 Chromosome 13, 108208181: 108208181
38 LIG4 NM_002312.3(LIG4): c.*352A> C single nucleotide variant Uncertain significance rs886049944 GRCh37 Chromosome 13, 108860529: 108860529
39 LIG4 NM_002312.3(LIG4): c.*306A> G single nucleotide variant Uncertain significance rs886049945 GRCh38 Chromosome 13, 108208227: 108208227
40 LIG4 NM_002312.3(LIG4): c.*306A> G single nucleotide variant Uncertain significance rs886049945 GRCh37 Chromosome 13, 108860575: 108860575
41 LIG4 NM_002312.3(LIG4): c.*242A> G single nucleotide variant Uncertain significance rs886049946 GRCh38 Chromosome 13, 108208291: 108208291
42 LIG4 NM_002312.3(LIG4): c.*242A> G single nucleotide variant Uncertain significance rs886049946 GRCh37 Chromosome 13, 108860639: 108860639
43 LIG4 NM_002312.3(LIG4): c.*166G> C single nucleotide variant Uncertain significance rs538355612 GRCh38 Chromosome 13, 108208367: 108208367
44 LIG4 NM_002312.3(LIG4): c.*166G> C single nucleotide variant Uncertain significance rs538355612 GRCh37 Chromosome 13, 108860715: 108860715
45 LIG4 NM_002312.3(LIG4): c.*56G> C single nucleotide variant Uncertain significance rs886049947 GRCh38 Chromosome 13, 108208477: 108208477
46 LIG4 NM_002312.3(LIG4): c.*56G> C single nucleotide variant Uncertain significance rs886049947 GRCh37 Chromosome 13, 108860825: 108860825
47 LIG4 NM_002312.3(LIG4): c.2518A> G (p.Ile840Val) single nucleotide variant Uncertain significance rs200369995 GRCh38 Chromosome 13, 108208751: 108208751
48 LIG4 NM_002312.3(LIG4): c.2518A> G (p.Ile840Val) single nucleotide variant Uncertain significance rs200369995 GRCh37 Chromosome 13, 108861099: 108861099
49 LIG4 NM_002312.3(LIG4): c.2274T> C (p.Tyr758=) single nucleotide variant Uncertain significance rs529756815 GRCh37 Chromosome 13, 108861343: 108861343
50 LIG4 NM_002312.3(LIG4): c.2274T> C (p.Tyr758=) single nucleotide variant Uncertain significance rs529756815 GRCh38 Chromosome 13, 108208995: 108208995

Expression for Severe Combined Immunodeficiency with Sensitivity to Ionizing...

Search GEO for disease gene expression data for Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation.

Pathways for Severe Combined Immunodeficiency with Sensitivity to Ionizing...

GO Terms for Severe Combined Immunodeficiency with Sensitivity to Ionizing...

Cellular components related to Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear chromosome, telomeric region GO:0000784 9.16 DCLRE1C LIG4
2 DNA ligase IV complex GO:0032807 8.96 LIG4 NHEJ1
3 nonhomologous end joining complex GO:0070419 8.8 DCLRE1C LIG4 NHEJ1

Biological processes related to Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to DNA damage stimulus GO:0006974 9.61 DCLRE1C LIG4 NHEJ1
2 DNA repair GO:0006281 9.54 DCLRE1C LIG4 NHEJ1
3 central nervous system development GO:0007417 9.48 LIG4 NHEJ1
4 B cell differentiation GO:0030183 9.46 DCLRE1C NHEJ1
5 DNA recombination GO:0006310 9.43 DCLRE1C LIG4 NHEJ1
6 chromosome organization GO:0051276 9.4 DCLRE1C LIG4
7 double-strand break repair via nonhomologous end joining GO:0006303 9.33 DCLRE1C LIG4 NHEJ1
8 V(D)J recombination GO:0033151 9.32 DCLRE1C LIG4
9 double-strand break repair GO:0006302 9.13 DCLRE1C LIG4 NHEJ1
10 response to ionizing radiation GO:0010212 8.8 DCLRE1C LIG4 NHEJ1

Sources for Severe Combined Immunodeficiency with Sensitivity to Ionizing...

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