DKCA1
MCID: DYS141
MIFTS: 38

Dyskeratosis Congenita, Autosomal Dominant 1 (DKCA1)

Categories: Blood diseases, Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Immune diseases, Liver diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Dyskeratosis Congenita, Autosomal Dominant 1

MalaCards integrated aliases for Dyskeratosis Congenita, Autosomal Dominant 1:

Name: Dyskeratosis Congenita, Autosomal Dominant 1 58 13
Dyskeratosis Congenita, Scoggins Type 58 12
Dkca1 58 12
Dyskeratosis Congenita, Autosomal Dominant, Type 1 41
Autosomal Dominant Dyskeratosis Congenita 1 12
Dyskeratosis Congenita, Autosomal Dominant 74

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
highly variable phenotype
variable penetrance and expressivity
genetic anticipation associated with progressive telomere shortening
skin manifestations may not be present
median age of diagnosis is 28 years
median survival is > 50 years


HPO:

33
dyskeratosis congenita, autosomal dominant 1:
Onset and clinical course phenotypic variability
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Dyskeratosis Congenita, Autosomal Dominant 1

OMIM : 58 Dyskeratosis congenita is a rare multisystem disorder caused by defective telomere maintenance. Clinical features are highly variable and include bone marrow failure, predisposition to malignancy, and pulmonary and hepatic fibrosis. The classic clinical triad of abnormal skin pigmentation, leukoplakia, and nail dystrophy is not always observed. Other features include premature graying of the hair, osteoporosis, epiphora, dental abnormalities and testicular atrophy, among others (review by Bessler et al., 2007 and Bessler et al., 2010). Hoyeraal-Hreidarsson syndrome (HHS) refers to a clinically severe variant of DKC that is characterized by multisystem involvement and early onset in utero. Patients with HHS show intrauterine growth retardation, microcephaly, delayed development, bone marrow failure resulting in immunodeficiency, cerebellar hypoplasia, and sometimes enteropathy. Death often occurs in childhood (summary by Walne et al., 2013). (127550)

MalaCards based summary : Dyskeratosis Congenita, Autosomal Dominant 1, also known as dyskeratosis congenita, scoggins type, is related to dyskeratosis congenita, x-linked and dyskeratosis congenita autosomal dominant. An important gene associated with Dyskeratosis Congenita, Autosomal Dominant 1 is TERC (Telomerase RNA Component), and among its related pathways/superpathways are Cell Cycle, Mitotic and Chromosome Maintenance. Affiliated tissues include skin, bone and bone marrow, and related phenotypes are ataxia and carious teeth

Disease Ontology : 12 A dyskeratosis congenita that has material basis in an autosomal dominant mutation of TERC on chromosome 3q26.2.

Related Diseases for Dyskeratosis Congenita, Autosomal Dominant 1

Diseases in the Dyskeratosis Congenita family:

Dyskeratosis Congenita, Autosomal Dominant 1 Dyskeratosis Congenita, Autosomal Recessive 1
Dyskeratosis Congenita, Autosomal Recessive 2 Dyskeratosis Congenita, Autosomal Recessive 3
Dyskeratosis Congenita, Autosomal Dominant 2 Dyskeratosis Congenita, Autosomal Dominant 3
Dyskeratosis Congenita, Autosomal Recessive 5 Dyskeratosis Congenita, Autosomal Recessive 6
Dyskeratosis Congenita, Autosomal Dominant 6 Dyskeratosis Congenita Autosomal Dominant
Dyskeratosis Congenita Autosomal Recessive

Diseases related to Dyskeratosis Congenita, Autosomal Dominant 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 21)
# Related Disease Score Top Affiliating Genes
1 dyskeratosis congenita, x-linked 31.4 TERC DKC1
2 dyskeratosis congenita autosomal dominant 31.4 TINF2 TERT TERC
3 dyskeratosis congenita, autosomal recessive 1 11.0
4 dyskeratosis congenita, autosomal recessive 2 11.0
5 dyskeratosis congenita, autosomal recessive 3 11.0
6 dyskeratosis congenita, autosomal dominant 2 11.0
7 dyskeratosis congenita, autosomal recessive 5 11.0
8 dyskeratosis congenita, autosomal recessive 6 11.0
9 dyskeratosis congenita, autosomal dominant 6 11.0
10 bone marrow failure syndrome 3 11.0
11 congenital intrauterine infection-like syndrome 10.0 TERC DKC1
12 torch syndrome 9.9 TERC DKC1
13 inherited bone marrow failure syndromes 9.9 TERT TERC
14 cervical intraepithelial neoplasia 9.8 TERT TERC
15 pancytopenia 9.8 TERT DKC1
16 pulmonary fibrosis, idiopathic 9.7 TERT TERC
17 fanconi anemia, complementation group a 9.7 TERC DKC1
18 pulmonary fibrosis 9.4 TINF2 TERT TERC
19 dyskeratosis congenita 9.2 TINF2 TERT TERC DKC1
20 revesz syndrome 9.2 TINF2 TERT TERC DKC1
21 aplastic anemia 9.1 TINF2 TERT TERC DKC1

Graphical network of the top 20 diseases related to Dyskeratosis Congenita, Autosomal Dominant 1:



Diseases related to Dyskeratosis Congenita, Autosomal Dominant 1

Symptoms & Phenotypes for Dyskeratosis Congenita, Autosomal Dominant 1

Human phenotypes related to Dyskeratosis Congenita, Autosomal Dominant 1:

33 (show all 25)
# Description HPO Frequency HPO Source Accession
1 ataxia 33 HP:0001251
2 carious teeth 33 HP:0000670
3 osteoporosis 33 HP:0000939
4 pulmonary fibrosis 33 HP:0002206
5 anemia 33 HP:0001903
6 bone marrow hypocellularity 33 HP:0005528
7 aplastic anemia 33 HP:0001915
8 myelodysplasia 33 HP:0002863
9 nail dystrophy 33 HP:0008404
10 specific learning disability 33 HP:0001328
11 alopecia 33 HP:0001596
12 cirrhosis 33 HP:0001394
13 thrombocytopenia 33 HP:0001873
14 premature graying of hair 33 HP:0002216
15 cerebellar hypoplasia 33 HP:0001321
16 lymphopenia 33 HP:0001888
17 sparse hair 33 HP:0008070
18 nail pits 33 HP:0001803
19 ridged nail 33 HP:0001807
20 oral leukoplakia 33 HP:0002745
21 squamous cell carcinoma of the skin 33 HP:0006739
22 interstitial pneumonitis 33 HP:0006515
23 dermal atrophy 33 HP:0004334
24 reticular hyperpigmentation 33 HP:0007588
25 premature loss of teeth 33 HP:0006480

Symptoms via clinical synopsis from OMIM:

58
Respiratory Lung:
pulmonary fibrosis
interstitial pneumonitis

Skin Nails Hair Nails:
nail dystrophy
nail pitting
nail ridging

Neoplasia:
squamous cell carcinoma of the skin

Head And Neck Mouth:
leukoplakia

Skin Nails Hair Skin:
reticulate hyperpigmentation
skin atrophy

Hematology:
anemia
pancytopenia
aplastic anemia
thrombocytopenia
lymphopenia
more
Skin Nails Hair Hair:
alopecia
sparse hair
hair loss
premature graying

Head And Neck Teeth:
early tooth loss
dental caries

Abdomen Liver:
liver cirrhosis

Laboratory Abnormalities:
shortened telomeres

Clinical features from OMIM:

127550

Drugs & Therapeutics for Dyskeratosis Congenita, Autosomal Dominant 1

Search Clinical Trials , NIH Clinical Center for Dyskeratosis Congenita, Autosomal Dominant 1

Genetic Tests for Dyskeratosis Congenita, Autosomal Dominant 1

Anatomical Context for Dyskeratosis Congenita, Autosomal Dominant 1

MalaCards organs/tissues related to Dyskeratosis Congenita, Autosomal Dominant 1:

42
Skin, Bone, Bone Marrow, Liver

Publications for Dyskeratosis Congenita, Autosomal Dominant 1

Variations for Dyskeratosis Congenita, Autosomal Dominant 1

ClinVar genetic disease variations for Dyskeratosis Congenita, Autosomal Dominant 1:

6 (show top 50) (show all 181)
# Gene Variation Type Significance SNP ID Assembly Location
1 TINF2 NM_001099274.2(TINF2): c.838A> G (p.Lys280Glu) single nucleotide variant Pathogenic rs121918543 GRCh37 Chromosome 14, 24709848: 24709848
2 TINF2 NM_001099274.2(TINF2): c.838A> G (p.Lys280Glu) single nucleotide variant Pathogenic rs121918543 GRCh38 Chromosome 14, 24240642: 24240642
3 TINF2 NM_001099274.2(TINF2): c.844C> A (p.Arg282Ser) single nucleotide variant Pathogenic rs121918545 GRCh37 Chromosome 14, 24709842: 24709842
4 TINF2 NM_001099274.2(TINF2): c.844C> A (p.Arg282Ser) single nucleotide variant Pathogenic rs121918545 GRCh38 Chromosome 14, 24240636: 24240636
5 TINF2 NM_001099274.2(TINF2): c.844C> T (p.Arg282Cys) single nucleotide variant Pathogenic rs121918545 GRCh37 Chromosome 14, 24709842: 24709842
6 TINF2 NM_001099274.2(TINF2): c.844C> T (p.Arg282Cys) single nucleotide variant Pathogenic rs121918545 GRCh38 Chromosome 14, 24240636: 24240636
7 TERC NR_001566.1(TERC): n.374_1194del821 deletion Pathogenic rs1553915517 GRCh37 Chromosome 3, 169481655: 169482475
8 TERC NR_001566.1(TERC): n.374_1194del821 deletion Pathogenic rs1553915517 GRCh38 Chromosome 3, 169763867: 169764687
9 TERC NR_001566.1(TERC): n.408C> G single nucleotide variant Pathogenic rs199422284 GRCh37 Chromosome 3, 169482441: 169482441
10 TERC NR_001566.1(TERC): n.408C> G single nucleotide variant Pathogenic rs199422284 GRCh38 Chromosome 3, 169764653: 169764653
11 TERC NR_001566.1(TERC): n.107_108delGCinsAG indel Pathogenic rs199476393 GRCh37 Chromosome 3, 169482741: 169482742
12 TERC NR_001566.1(TERC): n.107_108delGCinsAG indel Pathogenic rs199476393 GRCh38 Chromosome 3, 169764953: 169764954
13 TERC NR_001566.1(TERC): n.204C> G single nucleotide variant Pathogenic rs199422277 GRCh37 Chromosome 3, 169482645: 169482645
14 TERC NR_001566.1(TERC): n.204C> G single nucleotide variant Pathogenic rs199422277 GRCh38 Chromosome 3, 169764857: 169764857
15 TERC NR_001566.1(TERC): n.58G> A single nucleotide variant Benign rs113487931 GRCh37 Chromosome 3, 169482791: 169482791
16 TERC NR_001566.1(TERC): n.58G> A single nucleotide variant Benign rs113487931 GRCh38 Chromosome 3, 169765003: 169765003
17 TERC NR_001566.1(TERC): n.116C> T single nucleotide variant Pathogenic rs199422272 GRCh37 Chromosome 3, 169482733: 169482733
18 TERC NR_001566.1(TERC): n.116C> T single nucleotide variant Pathogenic rs199422272 GRCh38 Chromosome 3, 169764945: 169764945
19 TERT NM_198253.2(TERT): c.2706G> C (p.Lys902Asn) single nucleotide variant Pathogenic rs121918665 GRCh37 Chromosome 5, 1264656: 1264656
20 TERT NM_198253.2(TERT): c.2706G> C (p.Lys902Asn) single nucleotide variant Pathogenic rs121918665 GRCh38 Chromosome 5, 1264541: 1264541
21 TERC NR_001566.1(TERC): n.54_57delAACT deletion Pathogenic rs199422263 GRCh37 Chromosome 3, 169482792: 169482795
22 TERC NR_001566.1(TERC): n.54_57delAACT deletion Pathogenic rs199422263 GRCh38 Chromosome 3, 169765004: 169765007
23 TINF2 NM_001099274.2(TINF2): c.706C> T (p.Pro236Ser) single nucleotide variant Likely benign rs199422321 GRCh37 Chromosome 14, 24709980: 24709980
24 TINF2 NM_001099274.2(TINF2): c.706C> T (p.Pro236Ser) single nucleotide variant Likely benign rs199422321 GRCh38 Chromosome 14, 24240774: 24240774
25 TINF2 NM_001099274.2(TINF2): c.734C> A (p.Ser245Tyr) single nucleotide variant Conflicting interpretations of pathogenicity rs142777869 GRCh37 Chromosome 14, 24709952: 24709952
26 TINF2 NM_001099274.2(TINF2): c.734C> A (p.Ser245Tyr) single nucleotide variant Conflicting interpretations of pathogenicity rs142777869 GRCh38 Chromosome 14, 24240746: 24240746
27 TINF2 NM_001099274.2(TINF2): c.838A> T (p.Lys280Ter) single nucleotide variant Pathogenic rs121918543 GRCh37 Chromosome 14, 24709848: 24709848
28 TINF2 NM_001099274.2(TINF2): c.838A> T (p.Lys280Ter) single nucleotide variant Pathogenic rs121918543 GRCh38 Chromosome 14, 24240642: 24240642
29 TINF2 NM_001099274.2(TINF2): c.841G> A (p.Glu281Lys) single nucleotide variant Likely benign rs199422322 GRCh37 Chromosome 14, 24709845: 24709845
30 TINF2 NM_001099274.2(TINF2): c.841G> A (p.Glu281Lys) single nucleotide variant Likely benign rs199422322 GRCh38 Chromosome 14, 24240639: 24240639
31 TINF2 NM_001099274.2(TINF2): c.847C> G (p.Pro283Ala) single nucleotide variant Pathogenic rs199422311 GRCh37 Chromosome 14, 24709839: 24709839
32 TINF2 NM_001099274.2(TINF2): c.847C> G (p.Pro283Ala) single nucleotide variant Pathogenic rs199422311 GRCh38 Chromosome 14, 24240633: 24240633
33 TINF2 NM_001099274.2(TINF2): c.847C> T (p.Pro283Ser) single nucleotide variant Pathogenic rs199422311 GRCh37 Chromosome 14, 24709839: 24709839
34 TINF2 NM_001099274.2(TINF2): c.847C> T (p.Pro283Ser) single nucleotide variant Pathogenic rs199422311 GRCh38 Chromosome 14, 24240633: 24240633
35 TINF2 NM_001099274.2(TINF2): c.848C> A (p.Pro283His) single nucleotide variant Pathogenic rs199422313 GRCh37 Chromosome 14, 24709838: 24709838
36 TINF2 NM_001099274.2(TINF2): c.848C> A (p.Pro283His) single nucleotide variant Pathogenic rs199422313 GRCh38 Chromosome 14, 24240632: 24240632
37 TINF2 NM_001099274.1(TINF2): c.849dupC (p.Thr284Hisfs) duplication Pathogenic rs199422315 GRCh37 Chromosome 14, 24709837: 24709837
38 TINF2 NM_001099274.1(TINF2): c.849dupC (p.Thr284Hisfs) duplication Pathogenic rs199422315 GRCh38 Chromosome 14, 24240631: 24240631
39 TINF2 NM_001099274.2(TINF2): c.850A> G (p.Thr284Ala) single nucleotide variant Pathogenic rs199422314 GRCh37 Chromosome 14, 24709836: 24709836
40 TINF2 NM_001099274.2(TINF2): c.850A> G (p.Thr284Ala) single nucleotide variant Pathogenic rs199422314 GRCh38 Chromosome 14, 24240630: 24240630
41 TINF2 NM_001099274.2(TINF2): c.860T> C (p.Leu287Pro) single nucleotide variant Pathogenic rs199422316 GRCh37 Chromosome 14, 24709826: 24709826
42 TINF2 NM_001099274.2(TINF2): c.860T> C (p.Leu287Pro) single nucleotide variant Pathogenic rs199422316 GRCh38 Chromosome 14, 24240620: 24240620
43 TINF2 NM_001099274.2(TINF2): c.865_866delCCinsAG (p.Pro289Ser) indel Pathogenic rs199422318 GRCh37 Chromosome 14, 24709820: 24709821
44 TINF2 NM_001099274.2(TINF2): c.865_866delCCinsAG (p.Pro289Ser) indel Pathogenic rs199422318 GRCh38 Chromosome 14, 24240614: 24240615
45 TINF2 NM_001099274.2(TINF2): c.871A> G (p.Arg291Gly) single nucleotide variant Pathogenic rs199422319 GRCh37 Chromosome 14, 24709815: 24709815
46 TINF2 NM_001099274.2(TINF2): c.871A> G (p.Arg291Gly) single nucleotide variant Pathogenic rs199422319 GRCh38 Chromosome 14, 24240609: 24240609
47 TINF2 NM_001099274.1(TINF2): c.892delC (p.Gln298Argfs) deletion Pathogenic rs199422320 GRCh37 Chromosome 14, 24709794: 24709794
48 TINF2 NM_001099274.1(TINF2): c.892delC (p.Gln298Argfs) deletion Pathogenic rs199422320 GRCh38 Chromosome 14, 24240588: 24240588
49 TERT NM_198253.2(TERT): c.1378_1380delCAG (p.Gln460del) deletion Benign rs199422292 GRCh37 Chromosome 5, 1293621: 1293623
50 TERT NM_198253.2(TERT): c.1378_1380delCAG (p.Gln460del) deletion Benign rs199422292 GRCh38 Chromosome 5, 1293506: 1293508

Expression for Dyskeratosis Congenita, Autosomal Dominant 1

Search GEO for disease gene expression data for Dyskeratosis Congenita, Autosomal Dominant 1.

Pathways for Dyskeratosis Congenita, Autosomal Dominant 1

GO Terms for Dyskeratosis Congenita, Autosomal Dominant 1

Cellular components related to Dyskeratosis Congenita, Autosomal Dominant 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear chromosome, telomeric region GO:0000784 9.4 TERT TINF2
2 Cajal body GO:0015030 9.37 DKC1 TERC
3 chromosome, telomeric region GO:0000781 9.33 TERC TERT TINF2
4 nuclear telomere cap complex GO:0000783 9.32 TERT TINF2
5 box H/ACA telomerase RNP complex GO:0090661 9.26 DKC1 TERC
6 telomerase catalytic core complex GO:0000333 8.96 TERC TERT
7 telomerase holoenzyme complex GO:0005697 8.8 DKC1 TERC TERT

Biological processes related to Dyskeratosis Congenita, Autosomal Dominant 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to hypoxia GO:0071456 9.26 TERC TERT
2 DNA biosynthetic process GO:0071897 9.16 TERC TERT
3 negative regulation of cellular senescence GO:2000773 8.96 TERC TERT
4 telomere maintenance via telomerase GO:0007004 8.8 DKC1 TERC TERT

Molecular functions related to Dyskeratosis Congenita, Autosomal Dominant 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 telomeric DNA binding GO:0042162 9.32 TERT TINF2
2 telomerase RNA binding GO:0070034 9.26 DKC1 TERT
3 RNA-directed DNA polymerase activity GO:0003964 9.16 TERC TERT
4 telomerase RNA reverse transcriptase activity GO:0003721 8.96 TERC TERT
5 telomerase activity GO:0003720 8.8 DKC1 TERC TERT

Sources for Dyskeratosis Congenita, Autosomal Dominant 1

3 CDC
7 CNVD
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10 dbSNP
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17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
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45 MeSH
46 MESH via Orphanet
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58 OMIM
59 OMIM via Orphanet
63 PubMed
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70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
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75 UMLS via Orphanet
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