DKCA2
MCID: DYS143
MIFTS: 39

Dyskeratosis Congenita, Autosomal Dominant 2 (DKCA2)

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 2

MalaCards integrated aliases for Dyskeratosis Congenita, Autosomal Dominant 2:

Name: Dyskeratosis Congenita, Autosomal Dominant 2 57 13
Dyskeratosis Congenita, Autosomal Recessive, 4 72 29 6 70
Dyskeratosis Congenita, Autosomal Dominant, 2 72 29 6 70
Dkca2 57 12 72
Dkcb4 12 72
Dyskeratosis Congenita, Autosomal Dominant, Type 2 39
Dyskeratosis Congenita, Autosomal Recessive 4 57
Autosomal Recessive Dyskeratosis Congenita 4 12
Autosomal Dominant Dyskeratosis Congenita 2 12
Dyskeratosis Congenita Scoggins Type 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Miscellaneous:
genetic anticipation
variable penetrance and expressivity
two autosomal dominant families have been reported (as of may 2011)
highly variable phenotype and severity, even within families
age at onset ranges from childhood to adulthood
patients with the autosomal recessive disorder have a more severe phenotype

Inheritance:
autosomal recessive
autosomal dominant


HPO:

31
dyskeratosis congenita, autosomal dominant 2:
Inheritance autosomal dominant inheritance autosomal recessive inheritance genetic anticipation


Classifications:



Summaries for Dyskeratosis Congenita, Autosomal Dominant 2

UniProtKB/Swiss-Prot : 72 Dyskeratosis congenita, autosomal dominant, 2: A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.
Dyskeratosis congenita, autosomal recessive, 4: A severe form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.

MalaCards based summary : Dyskeratosis Congenita, Autosomal Dominant 2, also known as dyskeratosis congenita, autosomal recessive, 4, is related to dyskeratosis congenita, autosomal dominant 1 and dyskeratosis congenita autosomal dominant. An important gene associated with Dyskeratosis Congenita, Autosomal Dominant 2 is TERT (Telomerase Reverse Transcriptase). Affiliated tissues include bone marrow, bone and liver, and related phenotypes are failure to thrive and global developmental delay

Disease Ontology : 12 A dyskeratosis congenita that has material basis in an autosomal dominant mutation of TERT on chromosome 5p15.33.

OMIM® : 57 Dyskeratosis congenita is a multisystem disorder caused by defective telomere maintenance. Features are variable and include bone marrow failure, pulmonary and liver fibrosis, and premature graying of the hair (summary by Armanios et al., 2005). For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (127550). (613989) (Updated 20-May-2021)

Related Diseases for Dyskeratosis Congenita, Autosomal Dominant 2

Graphical network of the top 20 diseases related to Dyskeratosis Congenita, Autosomal Dominant 2:



Diseases related to Dyskeratosis Congenita, Autosomal Dominant 2

Symptoms & Phenotypes for Dyskeratosis Congenita, Autosomal Dominant 2

Human phenotypes related to Dyskeratosis Congenita, Autosomal Dominant 2:

31 (show all 22)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 31 HP:0001508
2 global developmental delay 31 HP:0001263
3 avascular necrosis 31 HP:0010885
4 abnormality of the dentition 31 HP:0000164
5 microcephaly 31 HP:0000252
6 short stature 31 HP:0004322
7 osteoporosis 31 HP:0000939
8 thrombocytopenia 31 HP:0001873
9 pulmonary fibrosis 31 HP:0002206
10 dilated cardiomyopathy 31 HP:0001644
11 premature graying of hair 31 HP:0002216
12 chronic diarrhea 31 HP:0002028
13 cerebellar hypoplasia 31 HP:0001321
14 nail dysplasia 31 HP:0002164
15 bone marrow hypocellularity 31 HP:0005528
16 nail dystrophy 31 HP:0008404
17 leukopenia 31 HP:0001882
18 palmoplantar hyperkeratosis 31 HP:0000972
19 urethral stricture 31 HP:0012227
20 esophageal stricture 31 HP:0002043
21 reticulated skin pigmentation 31 HP:0007427
22 aplastic anemia 31 HP:0001915

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Growth Height:
short stature

Hematology:
thrombocytopenia
pancytopenia
leukopenia
aplastic anemia
bone marrow failure

Cardiovascular Heart:
dilated cardiomyopathy
cardiac fibrosis

Skin Nails Hair Hair:
premature graying
gray forelock

Head And Neck Teeth:
abnormal dentition
tooth loss (seen in recessive form)

Growth Other:
failure to thrive (seen in recessive form)

Head And Neck Face:
elfin appearance (seen in recessive form)

Skin Nails Hair Skin:
leukoplakia (seen in recessive form)
reticulated pigmentation (seen in recessive form)
hyperkeratosis of the palms (seen in recessive form)

Skeletal Limbs:
avascular necrosis of the hip (seen in recessive form)

Neurologic Central Nervous System:
learning difficulties (seen in recessive form)
developmental delay (seen in recessive form)
cerebellar hypoplasia (seen in recessive form)

Skeletal:
osteoporosis

Respiratory Lung:
pulmonary fibrosis

Genitourinary Bladder:
urethral stricture

Laboratory Abnormalities:
shortened telomeres
decreased telomerase activity

Abdomen Liver:
liver fibrosis

Head And Neck Head:
microcephaly (seen in recessive form)

Head And Neck Mouth:
leukoplakia (seen in recessive form)
bluish discoloration of the tongue (seen in recessive form)

Abdomen Gastrointestinal:
esophageal stricture (seen in recessive form)
chronic diarrhea (seen in recessive form)

Skin Nails Hair Nails:
nail dystrophy (seen in recessive form)

Clinical features from OMIM®:

613989 (Updated 20-May-2021)

Drugs & Therapeutics for Dyskeratosis Congenita, Autosomal Dominant 2

Search Clinical Trials , NIH Clinical Center for Dyskeratosis Congenita, Autosomal Dominant 2

Genetic Tests for Dyskeratosis Congenita, Autosomal Dominant 2

Genetic tests related to Dyskeratosis Congenita, Autosomal Dominant 2:

# Genetic test Affiliating Genes
1 Dyskeratosis Congenita, Autosomal Dominant, 2 29 TERT
2 Dyskeratosis Congenita, Autosomal Recessive, 4 29

Anatomical Context for Dyskeratosis Congenita, Autosomal Dominant 2

MalaCards organs/tissues related to Dyskeratosis Congenita, Autosomal Dominant 2:

40
Bone Marrow, Bone, Liver, Eye, Tongue, Lung, Myeloid

Publications for Dyskeratosis Congenita, Autosomal Dominant 2

Articles related to Dyskeratosis Congenita, Autosomal Dominant 2:

(show all 15)
# Title Authors PMID Year
1
Expanding the clinical phenotype of autosomal dominant dyskeratosis congenita caused by TERT mutations. 6 57
18460650 2008
2
Complex inheritance pattern of dyskeratosis congenita in two families with 2 different mutations in the telomerase reverse transcriptase gene. 6 57
18042801 2008
3
Telomerase reverse-transcriptase homozygous mutations in autosomal recessive dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. 57 6
17785587 2007
4
Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita. 57 6
16247010 2005
5
Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes. 6
30995915 2019
6
Novel variants in Nordic patients referred for genetic testing of telomere-related disorders. 6
29483670 2018
7
Triallelic and epigenetic-like inheritance in human disorders of telomerase. 6
26024875 2015
8
Many disease-associated variants of hTERT retain high telomerase enzymatic activity. 6
23901009 2013
9
Telomerase gene mutations are associated with cirrhosis formation. 6
21520174 2011
10
Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells. 57
21602826 2011
11
Short telomeres resulting from heritable mutations in the telomerase reverse transcriptase gene predispose for a variety of malignancies. 6
19796246 2009
12
Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia. 6
19147845 2009
13
Adult-onset pulmonary fibrosis caused by mutations in telomerase. 6
17460043 2007
14
Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. 6
15814878 2005
15
Deletion of the telomerase reverse transcriptase gene and haploinsufficiency of telomere maintenance in Cri du chat syndrome. 6
12629597 2003

Variations for Dyskeratosis Congenita, Autosomal Dominant 2

ClinVar genetic disease variations for Dyskeratosis Congenita, Autosomal Dominant 2:

6 (show top 50) (show all 1089)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TERT NM_198253.3(TERT):c.2098C>T (p.Gln700Ter) SNV Pathogenic 242222 rs878855300 GRCh37: 5:1279438-1279438
GRCh38: 5:1279323-1279323
2 TERT NM_198253.3(TERT):c.1285G>T (p.Glu429Ter) SNV Pathogenic 973677 GRCh37: 5:1293716-1293716
GRCh38: 5:1293601-1293601
3 TERT NM_198253.3(TERT):c.1122_1134del (p.Thr375fs) Deletion Pathogenic 973897 GRCh37: 5:1293867-1293879
GRCh38: 5:1293752-1293764
4 TERT NM_198253.2(TERT):c.2706G>C (p.Lys902Asn) SNV Pathogenic 12735 rs121918665 GRCh37: 5:1264656-1264656
GRCh38: 5:1264541-1264541
5 TERT NM_198253.3(TERT):c.2286+1G>A SNV Pathogenic 1030450 GRCh37: 5:1278755-1278755
GRCh38: 5:1278640-1278640
6 TERT NM_198253.3(TERT):c.1892G>A (p.Arg631Gln) SNV Pathogenic 29899 rs199422294 GRCh37: 5:1280331-1280331
GRCh38: 5:1280216-1280216
7 TERT NM_198253.2(TERT):c.2431C>T (p.Arg811Cys) SNV Pathogenic 29900 rs199422301 GRCh37: 5:1271271-1271271
GRCh38: 5:1271156-1271156
8 TERT NM_198253.2(TERT):c.2701C>T (p.Arg901Trp) SNV Pathogenic 29901 rs199422304 GRCh37: 5:1264661-1264661
GRCh38: 5:1264546-1264546
9 TERT NM_198253.3(TERT):c.2110C>T (p.Pro704Ser) SNV Pathogenic 39108 rs199422297 GRCh37: 5:1279426-1279426
GRCh38: 5:1279311-1279311
10 TERT NM_198253.3(TERT):c.1234C>T (p.His412Tyr) SNV Pathogenic 12730 rs34094720 GRCh37: 5:1293767-1293767
GRCh38: 5:1293652-1293652
11 TERT NM_198253.3(TERT):c.336dup (p.Glu113fs) Duplication Pathogenic 410651 rs1060502990 GRCh37: 5:1294664-1294665
GRCh38: 5:1294549-1294550
12 TERT NM_198253.3(TERT):c.1044_1045CT[2] (p.Leu350fs) Microsatellite Pathogenic 539192 rs1554042899 GRCh37: 5:1293952-1293953
GRCh38: 5:1293837-1293838
13 TERT NM_198253.3(TERT):c.3108_3109CT[1] (p.Ile1036_Ser1037insTer) Microsatellite Pathogenic 539193 rs1554038257 GRCh37: 5:1255448-1255449
GRCh38: 5:1255333-1255334
14 LOC110806263 , TERT NM_198253.3(TERT):c.180G>A (p.Trp60Ter) SNV Pathogenic 568038 rs1554043139 GRCh37: 5:1294925-1294925
GRCh38: 5:1294810-1294810
15 TERT NM_198253.2(TERT):c.2320C>T (p.Arg774Ter) SNV Pathogenic 446373 rs770066110 GRCh37: 5:1272362-1272362
GRCh38: 5:1272247-1272247
16 TERT NC_000005.10:g.(?_1280152)_(1280344_?)del Deletion Pathogenic 584005 GRCh37: 5:1280267-1280459
GRCh38: 5:1280152-1280344
17 TERT NM_198253.3(TERT):c.688C>T (p.Arg230Ter) SNV Pathogenic 645232 rs989271195 GRCh37: 5:1294313-1294313
GRCh38: 5:1294198-1294198
18 TERT NC_000005.10:g.(?_1280148)_(1280348_?)del Deletion Pathogenic 654662 GRCh37: 5:1280263-1280463
GRCh38: 5:1280148-1280348
19 overlap with 17 genes NC_000005.10:g.(?_218349)_(1297373_?)del Deletion Pathogenic 831918 GRCh37: 5:218464-1297488
GRCh38:
20 overlap with 17 genes NC_000005.10:g.(?_218346)_(1295046_?)del Deletion Pathogenic 831255 GRCh37: 5:218461-1295161
GRCh38:
21 TERT NM_198253.3(TERT):c.1743G>A (p.Trp581Ter) SNV Pathogenic 842734 GRCh37: 5:1282570-1282570
GRCh38: 5:1282455-1282455
22 TERT NM_198253.3(TERT):c.1434G>A (p.Trp478Ter) SNV Pathogenic 843002 GRCh37: 5:1293567-1293567
GRCh38: 5:1293452-1293452
23 TERT NM_198253.3(TERT):c.2540dup (p.Asp848fs) Duplication Pathogenic 841032 GRCh37: 5:1268676-1268677
GRCh38: 5:1268561-1268562
24 TERT NM_198253.3(TERT):c.1156_1171del (p.Tyr386fs) Deletion Pathogenic 850129 GRCh37: 5:1293830-1293845
GRCh38: 5:1293715-1293730
25 TERT NM_198253.3(TERT):c.1712del (p.Asn571fs) Deletion Pathogenic 849023 GRCh37: 5:1282601-1282601
GRCh38: 5:1282486-1282486
26 TERT NM_198253.3(TERT):c.613dup (p.His205fs) Duplication Pathogenic 850035 GRCh37: 5:1294387-1294388
GRCh38: 5:1294272-1294273
27 TERT NM_198253.3(TERT):c.1685_1686del (p.Tyr562fs) Deletion Pathogenic 664605 rs1579580058 GRCh37: 5:1282627-1282628
GRCh38: 5:1282512-1282513
28 TERT NM_198253.3(TERT):c.1450G>T (p.Glu484Ter) SNV Pathogenic 656696 rs1561213355 GRCh37: 5:1293551-1293551
GRCh38: 5:1293436-1293436
29 TERT NM_198253.2(TERT):c.2320C>T (p.Arg774Ter) SNV Pathogenic 446373 rs770066110 GRCh37: 5:1272362-1272362
GRCh38: 5:1272247-1272247
30 TERT NM_198253.3(TERT):c.2704A>T (p.Lys902Ter) SNV Pathogenic 863437 GRCh37: 5:1264658-1264658
GRCh38: 5:1264543-1264543
31 TERT NM_198253.3(TERT):c.3211C>T (p.Gln1071Ter) SNV Pathogenic 937831 GRCh37: 5:1254567-1254567
GRCh38: 5:1254452-1254452
32 LOC110806263 , TERT NM_198253.3(TERT):c.162C>A (p.Cys54Ter) SNV Pathogenic 957034 GRCh37: 5:1294943-1294943
GRCh38: 5:1294828-1294828
33 TERT NM_198253.3(TERT):c.1574-1G>A SNV Likely pathogenic 952762 GRCh37: 5:1282740-1282740
GRCh38: 5:1282625-1282625
34 TERT NM_198253.3(TERT):c.2382+1G>C SNV Likely pathogenic 834313 GRCh37: 5:1272299-1272299
GRCh38: 5:1272184-1272184
35 TERT NM_198253.3(TERT):c.2936G>A (p.Arg979Gln) SNV Likely pathogenic 506255 rs765566930 GRCh37: 5:1260623-1260623
GRCh38: 5:1260508-1260508
36 LOC110806263 , TERT NM_198253.3(TERT):c.193C>G (p.Pro65Ala) SNV Likely pathogenic 471841 rs544215765 GRCh37: 5:1294912-1294912
GRCh38: 5:1294797-1294797
37 TERT NM_198253.3(TERT):c.2051A>G (p.Asp684Gly) SNV Likely pathogenic 446372 rs776981958 GRCh37: 5:1279485-1279485
GRCh38: 5:1279370-1279370
38 TERT NM_198253.3(TERT):c.1990G>C (p.Val664Leu) SNV Likely pathogenic 212400 rs797046042 GRCh37: 5:1279546-1279546
GRCh38: 5:1279431-1279431
39 TERT NM_198253.3(TERT):c.604G>A (p.Ala202Thr) SNV Conflicting interpretations of pathogenicity 12729 rs121918661 GRCh37: 5:1294397-1294397
GRCh38: 5:1294282-1294282
40 LOC110806263 , TERT NM_198253.3(TERT):c.159G>C (p.Gln53His) SNV Uncertain significance 410683 rs1060503006 GRCh37: 5:1294946-1294946
GRCh38: 5:1294831-1294831
41 LOC110806263 , TERT NM_198253.3(TERT):c.150G>A (p.Leu50=) SNV Uncertain significance 289326 rs886044153 GRCh37: 5:1294955-1294955
GRCh38: 5:1294840-1294840
42 TERT NM_198253.2(TERT):c.2287-5G>A SNV Uncertain significance 446374 rs561426406 GRCh37: 5:1272400-1272400
GRCh38: 5:1272285-1272285
43 TERT NM_198253.3(TERT):c.1393G>C (p.Val465Leu) SNV Uncertain significance 539202 rs758110675 GRCh37: 5:1293608-1293608
GRCh38: 5:1293493-1293493
44 TERT NM_198253.3(TERT):c.887A>C (p.His296Pro) SNV Uncertain significance 268080 rs778187343 GRCh37: 5:1294114-1294114
GRCh38: 5:1293999-1293999
45 TERT NM_198253.3(TERT):c.508G>A (p.Val170Met) SNV Uncertain significance 36947 rs387907248 GRCh37: 5:1294493-1294493
GRCh38: 5:1294378-1294378
46 TERT NM_198253.3(TERT):c.2221G>A (p.Val741Met) SNV Uncertain significance 471857 rs150819225 GRCh37: 5:1278821-1278821
GRCh38: 5:1278706-1278706
47 TERT NM_198253.3(TERT):c.1317_1319GGA[2] (p.Glu441del) Microsatellite Uncertain significance 212398 rs377639087 GRCh37: 5:1293676-1293678
GRCh38: 5:1293561-1293563
48 TERT and overlap with 2 gene(s) NC_000005.9:g.(?_1253837)_(1295110_?)dup Duplication Uncertain significance 539287 GRCh37: 5:1253837-1295110
GRCh38: 5:1253722-1294995
49 TERT and overlap with 2 gene(s) NC_000005.9:g.(?_1253833)_(1295161_?)dup Duplication Uncertain significance 584278 GRCh37: 5:1253833-1295161
GRCh38: 5:1253718-1295046
50 TERT NM_198253.3(TERT):c.1304T>A (p.Val435Glu) SNV Uncertain significance 565378 rs1561213530 GRCh37: 5:1293697-1293697
GRCh38: 5:1293582-1293582

UniProtKB/Swiss-Prot genetic disease variations for Dyskeratosis Congenita, Autosomal Dominant 2:

72
# Symbol AA change Variation ID SNP ID
1 TERT p.His412Tyr VAR_025149 rs34094720
2 TERT p.Lys902Asn VAR_036869 rs121918665
3 TERT p.Pro721Arg VAR_062538 rs199422299
4 TERT p.Arg811Cys VAR_062540 rs199422301
5 TERT p.Arg901Trp VAR_062541 rs199422304
6 TERT p.Arg979Trp VAR_062542 rs199422305
7 TERT p.Phe1127Leu VAR_062544 rs117627313
8 TERT p.Pro704Ser VAR_068793 rs199422297

Expression for Dyskeratosis Congenita, Autosomal Dominant 2

Search GEO for disease gene expression data for Dyskeratosis Congenita, Autosomal Dominant 2.

Pathways for Dyskeratosis Congenita, Autosomal Dominant 2

GO Terms for Dyskeratosis Congenita, Autosomal Dominant 2

Sources for Dyskeratosis Congenita, Autosomal Dominant 2

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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