DKCA1
MCID: DYS141
MIFTS: 42

Dyskeratosis Congenita, Autosomal Dominant 1 (DKCA1)

Categories: Blood diseases, Bone diseases, Cancer diseases, Eye diseases, Fetal diseases, Genetic diseases, Immune 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 57 29 13 6
Autosomal Dominant Dyskeratosis Congenita 1 12 15
Dyskeratosis Congenita, Scoggins Type 57 12
Dkca1 57 12
Dyskeratosis Congenita, Autosomal Dominant, Type 1 39
Dyskeratosis Congenita, Autosomal Dominant 71

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
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:

31
dyskeratosis congenita, autosomal dominant 1:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Dyskeratosis Congenita, Autosomal Dominant 1

OMIM® : 57 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) (Updated 05-Mar-2021)

MalaCards based summary : Dyskeratosis Congenita, Autosomal Dominant 1, also known as autosomal dominant dyskeratosis congenita 1, is related to dyskeratosis congenita, autosomal recessive 5 and dyskeratosis congenita, autosomal dominant 2. An important gene associated with Dyskeratosis Congenita, Autosomal Dominant 1 is TERC (Telomerase RNA Component), and among its related pathways/superpathways is Lung fibrosis. Affiliated tissues include bone marrow, skin and bone, 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 29)
# Related Disease Score Top Affiliating Genes
1 dyskeratosis congenita, autosomal recessive 5 31.5 RTEL1-TNFRSF6B RTEL1
2 dyskeratosis congenita, autosomal dominant 2 31.3 TERT LOC110806263
3 dyskeratosis congenita, x-linked 31.3 TINF2 TERT TERC
4 dyskeratosis congenita autosomal dominant 29.1 TINF2 TGM1 TERT TERC RTEL1-TNFRSF6B RTEL1
5 dyskeratosis congenita, autosomal recessive 1 10.9
6 dyskeratosis congenita, autosomal recessive 2 10.9
7 dyskeratosis congenita, autosomal recessive 3 10.9
8 dyskeratosis congenita, autosomal recessive 6 10.9
9 dyskeratosis congenita, autosomal dominant 6 10.9
10 bone marrow failure syndrome 3 10.9
11 pulmonary fibrosis and/or bone marrow failure, telomere-related, 2 10.2 TERC LOC110806306
12 pulmonary fibrosis and/or bone marrow failure, telomere-related, 3 10.2 RTEL1-TNFRSF6B RTEL1
13 inherited bone marrow failure syndromes 10.1 TERT TERC
14 postinflammatory pulmonary fibrosis 10.1 TERT TERC
15 dyskeratosis congenita autosomal recessive 10.0 TERT RTEL1-TNFRSF6B RTEL1
16 coats disease 10.0 TINF2 TERC RTEL1
17 cervical intraepithelial neoplasia 10.0 TERT TERC
18 shwachman-diamond syndrome 1 9.9 TINF2 TERT TERC
19 pulmonary fibrosis 9.8 TINF2 TERT TERC RTEL1
20 hoyeraal hreidarsson syndrome 9.8 TINF2 TERT TERC RTEL1
21 dyskeratosis congenita, autosomal dominant 3 9.8 TINF2 TGM1
22 melanoma, cutaneous malignant 1 9.8 TINF2 TERT TERC RTEL1
23 pulmonary fibrosis and/or bone marrow failure, telomere-related, 1 9.8 TERT RTEL1-TNFRSF6B RTEL1 LOC110806263
24 acute interstitial pneumonia 9.8 TERT TERC RTEL1-TNFRSF6B LOC110806263
25 revesz syndrome 9.5 TINF2 TGM1 TERT TERC RTEL1
26 myelodysplastic syndrome 9.5 TERT TERC RTEL1 MECOM
27 aplastic anemia 9.4 TINF2 TERT TERC RTEL1 LOC110806306 LOC110806263
28 pulmonary fibrosis, idiopathic 9.4 TINF2 TERT TERC RTEL1-TNFRSF6B RTEL1 LOC110806263
29 dyskeratosis congenita 8.0 TINF2 TGM1 TERT TERC RTEL1-TNFRSF6B RTEL1

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:

31 (show all 25)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 HP:0001251
2 carious teeth 31 HP:0000670
3 anemia 31 HP:0001903
4 osteoporosis 31 HP:0000939
5 specific learning disability 31 HP:0001328
6 alopecia 31 HP:0001596
7 cirrhosis 31 HP:0001394
8 thrombocytopenia 31 HP:0001873
9 pulmonary fibrosis 31 HP:0002206
10 myelodysplasia 31 HP:0002863
11 lymphopenia 31 HP:0001888
12 premature graying of hair 31 HP:0002216
13 cerebellar hypoplasia 31 HP:0001321
14 sparse hair 31 HP:0008070
15 squamous cell carcinoma of the skin 31 HP:0006739
16 ridged nail 31 HP:0001807
17 oral leukoplakia 31 HP:0002745
18 bone marrow hypocellularity 31 HP:0005528
19 nail dystrophy 31 HP:0008404
20 nail pits 31 HP:0001803
21 premature loss of teeth 31 HP:0006480
22 dermal atrophy 31 HP:0004334
23 reticular hyperpigmentation 31 HP:0007588
24 interstitial pneumonitis 31 HP:0006515
25 aplastic anemia 31 HP:0001915

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Hematology:
anemia
thrombocytopenia
lymphopenia
pancytopenia
aplastic anemia
more
Respiratory Lung:
pulmonary fibrosis
interstitial pneumonitis

Skin Nails Hair Nails:
nail dystrophy
nail pitting
nail ridging

Head And Neck Mouth:
leukoplakia

Skin Nails Hair Skin:
reticulate hyperpigmentation
skin atrophy

Skin Nails Hair Hair:
alopecia
sparse hair
hair loss
premature graying

Neoplasia:
squamous cell carcinoma of the skin

Head And Neck Teeth:
early tooth loss
dental caries

Abdomen Liver:
liver cirrhosis

Laboratory Abnormalities:
shortened telomeres

Clinical features from OMIM®:

127550 (Updated 05-Mar-2021)

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

Genetic tests related to Dyskeratosis Congenita, Autosomal Dominant 1:

# Genetic test Affiliating Genes
1 Dyskeratosis Congenita, Autosomal Dominant 1 29 TERC TERT TINF2

Anatomical Context for Dyskeratosis Congenita, Autosomal Dominant 1

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

40
Bone Marrow, Skin, Bone, Liver

Publications for Dyskeratosis Congenita, Autosomal Dominant 1

Articles related to Dyskeratosis Congenita, Autosomal Dominant 1:

(show all 15)
# Title Authors PMID Year
1
Revertant somatic mosaicism by mitotic recombination in dyskeratosis congenita. 57 6
22341970 2012
2
The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. 6 57
11574891 2001
3
Constitutional mutations in RTEL1 cause severe dyskeratosis congenita. 57
23453664 2013
4
Dyskeratosis congenita. 57
20493861 2010
5
Short telomeres are sufficient to cause the degenerative defects associated with aging. 57
19944403 2009
6
Engineered telomere degradation models dyskeratosis congenita. 57
18550783 2008
7
Characterization of primitive hematopoietic cells from patients with dyskeratosis congenita. 57
18310499 2008
8
Dyskeratosis congenita: a genetic disorder of many faces. 57
18005359 2008
9
Dysfunctional telomeres and dyskeratosis congenita. 57
17650438 2007
10
Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC. 57
15098033 2004
11
Dyskeratosis congenita with linear areas of severe cutaneous involvement. 57
9489792 1998
12
Segmental forms of autosomal dominant skin disorders: different types of severity reflect different states of zygosity. 57
8958340 1996
13
Cytogenetic studies of skin fibroblast cultures from a karyotypically normal female with dyskeratosis congenita. 57
1563086 1992
14
Dyskeratosis congenita. 57
3236366 1988
15
Dyskeratosis congenita: an autosomal dominant disorder. 57
7096665 1982

Variations for Dyskeratosis Congenita, Autosomal Dominant 1

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

6 (show top 50) (show all 203)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TERC NR_001566.1(TERC):n.374_1194del821 Deletion Pathogenic 7319 rs1553915517 3:169481651-169482471 3:169763863-169764683
2 TERC NR_001566.1(TERC):n.408C>G SNV Pathogenic 7320 rs199422284 3:169482441-169482441 3:169764653-169764653
3 TINF2 NM_001099274.3(TINF2):c.706C>T (p.Pro236Ser) SNV Pathogenic 38915 rs199422321 14:24709980-24709980 14:24240774-24240774
4 TINF2 NM_001099274.3(TINF2):c.734C>A (p.Ser245Tyr) SNV Pathogenic 38916 rs142777869 14:24709952-24709952 14:24240746-24240746
5 TINF2 NM_001099274.3(TINF2):c.838A>G (p.Lys280Glu) SNV Pathogenic 5624 rs121918543 14:24709848-24709848 14:24240642-24240642
6 TINF2 NM_001099274.3(TINF2):c.838A>T (p.Lys280Ter) SNV Pathogenic 38917 rs121918543 14:24709848-24709848 14:24240642-24240642
7 TGM1 NM_001099274.3(TINF2):c.841G>A (p.Glu281Lys) SNV Pathogenic 38918 rs199422322 14:24709845-24709845 14:24240639-24240639
8 TINF2 NM_001099274.3(TINF2):c.844C>A (p.Arg282Ser) SNV Pathogenic 5626 rs121918545 14:24709842-24709842 14:24240636-24240636
9 TINF2 NM_001099274.3(TINF2):c.844C>T (p.Arg282Cys) SNV Pathogenic 5627 rs121918545 14:24709842-24709842 14:24240636-24240636
10 TINF2 NM_001099274.3(TINF2):c.847C>G (p.Pro283Ala) SNV Pathogenic 38919 rs199422311 14:24709839-24709839 14:24240633-24240633
11 TINF2 NM_001099274.3(TINF2):c.847C>T (p.Pro283Ser) SNV Pathogenic 38920 rs199422311 14:24709839-24709839 14:24240633-24240633
12 TINF2 NM_001099274.3(TINF2):c.848C>A (p.Pro283His) SNV Pathogenic 38921 rs199422313 14:24709838-24709838 14:24240632-24240632
13 TINF2 NM_001099274.3(TINF2):c.849dup (p.Thr284fs) Duplication Pathogenic 38922 rs199422315 14:24709836-24709837 14:24240630-24240631
14 TINF2 NM_001099274.3(TINF2):c.850A>G (p.Thr284Ala) SNV Pathogenic 38923 rs199422314 14:24709836-24709836 14:24240630-24240630
15 TINF2 NM_001099274.3(TINF2):c.860T>C (p.Leu287Pro) SNV Pathogenic 38924 rs199422316 14:24709826-24709826 14:24240620-24240620
16 TINF2 NM_001099274.3(TINF2):c.865_866delinsAG (p.Pro289Ser) Indel Pathogenic 38926 rs199422318 14:24709820-24709821 14:24240614-24240615
17 TINF2 NM_001099274.3(TINF2):c.871A>G (p.Arg291Gly) SNV Pathogenic 38927 rs199422319 14:24709815-24709815 14:24240609-24240609
18 TINF2 NM_001099274.3(TINF2):c.892del (p.Gln298fs) Deletion Pathogenic 38928 rs199422320 14:24709794-24709794 14:24240588-24240588
19 TERT TERT:c.1710G>Y (p.Lys570Asn) SNV Pathogenic 39103 rs1554041299 5:1282603-1282603 5:1282488-1282488
20 TERT NM_198253.3(TERT):c.2029G>T (p.Gly677Cys) SNV Pathogenic 39105 rs199422296 5:1279507-1279507 5:1279392-1279392
21 TERT NM_198253.3(TERT):c.2045G>A (p.Gly682Asp) SNV Pathogenic 39106 rs199422295 5:1279491-1279491 5:1279376-1279376
22 TERT NM_198253.3(TERT):c.2110C>T (p.Pro704Ser) SNV Pathogenic 39108 rs199422297 5:1279426-1279426 5:1279311-1279311
23 TERT NM_198253.3(TERT):c.2162C>G (p.Pro721Arg) SNV Pathogenic 39110 rs199422299 5:1278880-1278880 5:1278765-1278765
24 TERT NM_198253.3(TERT):c.2177C>T (p.Thr726Met) SNV Pathogenic 39111 rs149566858 5:1278865-1278865 5:1278750-1278750
25 TERT NM_198253.2(TERT):c.2706G>C (p.Lys902Asn) SNV Pathogenic 12735 rs121918665 5:1264656-1264656 5:1264541-1264541
26 TERT NM_198253.3(TERT):c.2935C>T (p.Arg979Trp) SNV Pathogenic 39118 rs199422305 5:1260624-1260624 5:1260509-1260509
27 TERC NR_001566.1(TERC):n.100T>A SNV Pathogenic 39280 rs199422269 3:169482749-169482749 3:169764961-169764961
28 TERC NR_001566.1(TERC):n.116C>T SNV Pathogenic 7326 rs199422272 3:169482733-169482733 3:169764945-169764945
29 TERC NR_001566.1(TERC):n.143G>A SNV Pathogenic 39282 rs199422274 3:169482706-169482706 3:169764918-169764918
30 TERC NR_001566.1(TERC):n.204C>G SNV Pathogenic 7322 rs199422277 3:169482645-169482645 3:169764857-169764857
31 TERC NR_001566.1(TERC):n.216_229del Deletion Pathogenic 39285 rs199422278 3:169482620-169482633 3:169764832-169764845
32 TERC NR_001566.1(TERC):n.410C>G SNV Pathogenic 39295 rs199422286 3:169482439-169482439 3:169764651-169764651
33 LOC110806306 NR_001566.1(TERC):n.48A>G SNV Pathogenic 39297 rs199422262 3:169482801-169482801 3:169765013-169765013
34 LOC110806306 NR_001566.1(TERC):n.53_87del Deletion Pathogenic 39299 rs199422264 3:169482762-169482796 3:169764974-169765008
35 TERC NR_001566.1(TERC):n.79del Deletion Pathogenic 39300 rs199422266 3:169482770-169482770 3:169764982-169764982
36 TERC NR_001566.1(TERC):n.96_97del Deletion Pathogenic 39301 rs199422267 3:169482752-169482753 3:169764964-169764965
37 ACTRT3 NM_032487.4(ACTRT3):c.831_*2687del2976 Deletion Pathogenic 40977 3:169482529-169485504 3:169764741-169767716
38 LOC110806306 NR_001566.1(TERC):n.2G>C SNV Pathogenic 39288 rs199422257 3:169482847-169482847 3:169765059-169765059
39 LOC110806306 NR_001566.1(TERC):n.35C>T SNV Pathogenic 39292 rs199422260 3:169482814-169482814 3:169765026-169765026
40 TERC NR_001566.1(TERC):n.107_108delinsAG Indel Pathogenic 7321 rs199476393 3:169482741-169482742 3:169764953-169764954
41 LOC110806306 NR_001566.1(TERC):n.54_57del Deletion Pathogenic 30265 rs199422263 3:169482792-169482795 3:169765004-169765007
42 TERC NR_001566.1(TERC):n.-240_-239del Microsatellite Pathogenic 39279 rs199422255 3:169483087-169483088 3:169765299-169765300
43 TERC NR_001566.1(TERC):n.110_113del Deletion Pathogenic 7325 rs199422270 3:169482736-169482739 3:169764948-169764951
44 LOC110806306 NR_001566.1(TERC):n.67del Deletion Pathogenic 950972 3:169482782-169482782 3:169764994-169764994
45 TERC NC_000003.12:g.(?_169481351)_(169484227_?)del Deletion Likely pathogenic 972905 3:169481351-169484227
46 TERC NM_004991.4(MECOM):c.38-100973_38-100960del Deletion Likely pathogenic 972906 3:169200272-169200285 3:169482484-169482497
47 TERC NR_001566.1(TERC):n.443C>A SNV Likely pathogenic 436977 rs1553915577 3:169482406-169482406 3:169764618-169764618
48 TERC NR_001566.1(TERC):n.306T>G SNV Likely pathogenic 436976 rs1553915591 3:169482543-169482543 3:169764755-169764755
49 TERC NM_004991.4(MECOM):c.38-101211_38-101210del Deletion Likely pathogenic 916672 3:169200522-169200523 3:169482734-169482735
50 TERC NM_004991.4(MECOM):c.38-101210del Deletion Likely pathogenic 916673 3:169200522-169200522 3:169482734-169482734

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

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

# Super pathways Score Top Affiliating Genes
1 10.42 TERT RTEL1

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 telomerase holoenzyme complex GO:0005697 9.26 TERT TERC
2 chromosome, telomeric region GO:0000781 9.26 TINF2 TERT TERC RTEL1
3 nuclear telomere cap complex GO:0000783 9.16 TINF2 TERT
4 telomerase catalytic core complex GO:0000333 8.62 TERT TERC

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

# Name GO ID Score Top Affiliating Genes
1 nucleobase-containing compound metabolic process GO:0006139 9.37 RTEL1-TNFRSF6B RTEL1
2 DNA biosynthetic process GO:0071897 9.32 TERT TERC
3 negative regulation of cellular senescence GO:2000773 9.26 TERT TERC
4 telomere maintenance via telomerase GO:0007004 9.16 TERT TERC
5 regulation of double-strand break repair via homologous recombination GO:0010569 8.96 RTEL1-TNFRSF6B RTEL1
6 telomere maintenance GO:0000723 8.8 TERT RTEL1-TNFRSF6B RTEL1

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

# Name GO ID Score Top Affiliating Genes
1 4 iron, 4 sulfur cluster binding GO:0051539 9.4 RTEL1-TNFRSF6B RTEL1
2 telomeric DNA binding GO:0042162 9.37 TINF2 TERT
3 DNA polymerase binding GO:0070182 9.32 TERC RTEL1
4 hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides GO:0016818 9.26 RTEL1-TNFRSF6B RTEL1
5 RNA-directed DNA polymerase activity GO:0003964 9.16 TERT TERC
6 telomerase activity GO:0003720 8.96 TERT TERC
7 telomerase RNA reverse transcriptase activity GO:0003721 8.62 TERT TERC

Sources for Dyskeratosis Congenita, Autosomal Dominant 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....