MCID: DNL001
MIFTS: 39

Dna Ligase Iv Deficiency malady

Genetic diseases, Blood diseases, Cancer diseases, Rare diseases, Immune diseases categories
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Summaries for Dna Ligase Iv Deficiency

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Disease Ontology:8 A combined t cell and b cell immunodeficiency that is caused by a mutatino in the lig4 gene, a dna ligase, encoding a protein essential for v(d)j recombination and dna double-strand break (dsb) repair through nonhomologous end joining (nhej). patients present with immunodeficiency and developmental and growth delay.

MalaCards based summary: Dna Ligase Iv Deficiency, also known as lig4 syndrome, is related to nijmegen breakage syndrome and severe combined immunodeficiency, and has symptoms including microcephaly, immunodeficiency/increased susceptibility to infections/recurrent infections and autosomal recessive inheritance. An important gene associated with Dna Ligase Iv Deficiency is LIG4 (ligase IV, DNA, ATP-dependent), and among its related pathways is Non-homologous end-joining. Affiliated tissues include b cells, t cells and skin, and related mouse phenotype tumorigenesis.

Description from OMIM:46 606593

Aliases & Classifications for Dna Ligase Iv Deficiency

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Sources:
8Disease Ontology, 10DISEASES, 48Orphanet, 9diseasecard, 20GeneTests, 22GTR, 46OMIM, 44Novoseek, 62UMLS, 26ICD10 via Orphanet
See all sources

Dna Ligase Iv Deficiency, Aliases & Descriptions:

Name: Dna Ligase Iv Deficiency 8 10 48
Lig4 Syndrome 8 9 20 22 46 44 48 62
 
Ligase 4 Syndrome 48


Classifications:



Characteristics (Orphanet epidemiological data):

48
lig4 syndrome:
Inheritance: Autosomal recessive; Prevalence: <1/1000000; Age of onset: Neonatal/infancy; Age of death: Young adult


External Ids:

Disease Ontology8 DOID:0060021
OMIM46 606593
ICD10 via Orphanet26 D81.1

Related Diseases for Dna Ligase Iv Deficiency

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Diseases related to Dna Ligase Iv Deficiency via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

idRelated DiseaseScoreTop Affiliating Genes
1nijmegen breakage syndrome29.7LIG4, NHEJ1
2severe combined immunodeficiency10.1LIG4
3b-cell lymphomas10.1
4seckel syndrome10.1

Symptoms for Dna Ligase Iv Deficiency

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Clinical features from OMIM:

606593

Symptoms:

48 (show all 34)
  • microcephaly
  • immunodeficiency/increased susceptibility to infections/recurrent infections
  • autosomal recessive inheritance
  • chromosome breakage
  • failure to thrive/difficulties for feeding in infancy/growth delay
  • brachycephaly/flat occiput
  • narrow forehead
  • low hair line-front
  • upslanted palpebral fissures/mongoloid slanting palpebral fissures
  • micrognathia/retrognathia/micrognathism/retrognathism
  • epicanthic folds
  • telecanthus/canthal dystopy
  • long/large/bulbous nose
  • broad nasal root
  • thin/retracted lips
  • anomalies of skin, subcutaneous tissue and mucosae
  • skin photosensitivity
  • erythema/erythematous lesions/erythroderma/polymorphous erythema
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • bone marrow failure/pancytopenia
  • lymphoma
  • acute leukemia
  • clinodactyly of fifth finger
  • telangiectasiae of the skin
  • malabsorption/chronic diarrhea/steatorrhea
  • hepatomegaly/liver enlargement (excluding storage disease)
  • lymphadenopathy/polyadenopathies
  • micropenis/small penis/agenesis
  • undescended/ectopic testes/cryptorchidia/unfixed testes
  • hypothyroidy
  • insulin-independent/type 2 diabetes
  • anomalies of bones/skeletal anomalies
  • severe combined immune deficiency syndrome/scid
  • hyperleukocytosis/leukocytosis

HPO human phenotypes related to Dna Ligase Iv Deficiency:

(show all 28)
id Description Frequency HPO Source Accession
1 microcephaly hallmark (90%) HP:0000252
2 abnormality of chromosome stability hallmark (90%) HP:0003220
3 thin vermilion border typical (50%) HP:0000233
4 epicanthus typical (50%) HP:0000286
5 low anterior hairline typical (50%) HP:0000294
6 narrow forehead typical (50%) HP:0000341
7 micrognathia typical (50%) HP:0000347
8 wide nasal bridge typical (50%) HP:0000431
9 telecanthus typical (50%) HP:0000506
10 upslanted palpebral fissure typical (50%) HP:0000582
11 cutaneous photosensitivity typical (50%) HP:0000992
12 acute leukemia typical (50%) HP:0002488
13 abnormality of calvarial morphology typical (50%) HP:0002648
14 lymphoma typical (50%) HP:0002665
15 abnormal nasal morphology typical (50%) HP:0005105
16 bone marrow hypocellularity typical (50%) HP:0005528
17 cognitive impairment typical (50%) HP:0100543
18 cryptorchidism occasional (7.5%) HP:0000028
19 hypothyroidism occasional (7.5%) HP:0000821
20 leukocytosis occasional (7.5%) HP:0001974
21 malabsorption occasional (7.5%) HP:0002024
22 hepatomegaly occasional (7.5%) HP:0002240
23 lymphadenopathy occasional (7.5%) HP:0002716
24 clinodactyly of the 5th finger occasional (7.5%) HP:0004209
25 severe combined immunodeficiency occasional (7.5%) HP:0004430
26 type ii diabetes mellitus occasional (7.5%) HP:0005978
27 hypoplasia of penis occasional (7.5%) HP:0008736
28 teleangiectasia of the skin occasional (7.5%) HP:0100585

Drugs & Therapeutics for Dna Ligase Iv Deficiency

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Drug clinical trials:

Search ClinicalTrials for Dna Ligase Iv Deficiency

Search NIH Clinical Center for Dna Ligase Iv Deficiency

Genetic Tests for Dna Ligase Iv Deficiency

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Genetic tests related to Dna Ligase Iv Deficiency:

id Genetic test Affiliating Genes
1 Lig4 Syndrome20 22 LIG4

Anatomical Context for Dna Ligase Iv Deficiency

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MalaCards organs/tissues related to Dna Ligase Iv Deficiency:

32
B cells, T cells, Skin, Bone, Testes, Bone marrow, Liver

Animal Models for Dna Ligase Iv Deficiency or affiliated genes

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MGI Mouse Phenotypes related to Dna Ligase Iv Deficiency:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00020069.1LIG4, NHEJ1

Publications for Dna Ligase Iv Deficiency

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Articles related to Dna Ligase Iv Deficiency:

idTitleAuthorsYear
1
A novel mutation in a family with DNA ligase IV deficiency syndrome. (19418549)
2009
2
Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure. (17224058)
2007
3
Ku80- and DNA ligase IV-deficient plants are sensitive to ionizing radiation and defective in T-DNA integration. (12753583)
2003
4
The embryonic lethality in DNA ligase IV-deficient mice is rescued by deletion of Ku: implications for unifying the heterogeneous phenotypes of NHEJ mutants. (12531011)
2002
5
DNA ligase IV deficiency in mice leads to defective neurogenesis and embryonic lethality via the p53 pathway. (10911993)
2000

Variations for Dna Ligase Iv Deficiency

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UniProtKB/Swiss-Prot genetic disease variations for Dna Ligase Iv Deficiency:

64
id Symbol AA change Variation ID SNP ID
1LIG4p.Arg278HisVAR_012774
2LIG4p.Gly469GluVAR_012775

Clinvar genetic disease variations for Dna Ligase Iv Deficiency:

6
id Gene Name Type Significance SNP ID Assembly Location
1LIG4NM_002312.3(LIG4): c.1738C> T (p.Arg580Ter)single nucleotide variantPathogenicrs104894418GRCh37Chr 13, 108861879: 108861879
2LIG4NM_002312.3(LIG4): c.2440C> T (p.Arg814Ter)single nucleotide variantPathogenicrs104894419GRCh37Chr 13, 108861177: 108861177
3LIG4NM_002312.3(LIG4): c.1406G> A (p.Gly469Glu)single nucleotide variantPathogenicrs104894420GRCh37Chr 13, 108862211: 108862211
4LIG4NM_002312.3(LIG4): c.833G> A (p.Arg278His)single nucleotide variantPathogenicrs104894421GRCh37Chr 13, 108862784: 108862784
5LIG4NM_002312.3(LIG4): c.1298_1300delAAC (p.Gln433del)deletionPathogenicGRCh37Chr 13, 108862317: 108862319

Expression for genes affiliated with Dna Ligase Iv Deficiency

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Expression patterns in normal tissues for genes affiliated with Dna Ligase Iv Deficiency

Search GEO for disease gene expression data for Dna Ligase Iv Deficiency.

Pathways for genes affiliated with Dna Ligase Iv Deficiency

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Pathways related to Dna Ligase Iv Deficiency according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
Non-homologous end joining37
DNA damage NHEJ mechanisms of DSBs repair60
9.1LIG4, NHEJ1

Compounds for genes affiliated with Dna Ligase Iv Deficiency

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GO Terms for genes affiliated with Dna Ligase Iv Deficiency

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Cellular components related to Dna Ligase Iv Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1nonhomologous end joining complexGO:0704199.1LIG4, NHEJ1

Biological processes related to Dna Ligase Iv Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1central nervous system developmentGO:0074179.1LIG4, NHEJ1
2double-strand break repair via nonhomologous end joiningGO:0063038.8LIG4, NHEJ1

Molecular functions related to Dna Ligase Iv Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1DNA bindingGO:0036779.1LIG4, NHEJ1

Products for genes affiliated with Dna Ligase Iv Deficiency

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  • Antibodies
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Sources for Dna Ligase Iv Deficiency

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet