DKCA2
MCID: DYS143
MIFTS: 37

Dyskeratosis Congenita, Autosomal Dominant 2 (DKCA2)

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 2

MalaCards integrated aliases for Dyskeratosis Congenita, Autosomal Dominant 2:

Name: Dyskeratosis Congenita, Autosomal Dominant 2 56 13
Dyskeratosis Congenita, Autosomal Recessive, 4 73 29 6 71
Dyskeratosis Congenita, Autosomal Dominant, 2 73 29 6 71
Dkca2 56 12 73
Dkcb4 12 73
Dyskeratosis Congenita, Autosomal Dominant, Type 2 39
Dyskeratosis Congenita, Autosomal Recessive 4 56
Autosomal Recessive Dyskeratosis Congenita 4 12
Autosomal Dominant Dyskeratosis Congenita 2 12
Dyskeratosis Congenita Scoggins Type 73

Characteristics:

OMIM:

56
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 : 73 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 and dyskeratosis congenita, autosomal dominant 1. 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 : 56 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)

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 abnormality of the dentition 31 HP:0000164
4 short stature 31 HP:0004322
5 microcephaly 31 HP:0000252
6 osteoporosis 31 HP:0000939
7 pulmonary fibrosis 31 HP:0002206
8 bone marrow hypocellularity 31 HP:0005528
9 aplastic anemia 31 HP:0001915
10 nail dystrophy 31 HP:0008404
11 thrombocytopenia 31 HP:0001873
12 dilated cardiomyopathy 31 HP:0001644
13 premature graying of hair 31 HP:0002216
14 cerebellar hypoplasia 31 HP:0001321
15 chronic diarrhea 31 HP:0002028
16 nail dysplasia 31 HP:0002164
17 leukopenia 31 HP:0001882
18 palmoplantar hyperkeratosis 31 HP:0000972
19 urethral stricture 31 HP:0012227
20 reticulated skin pigmentation 31 HP:0007427
21 esophageal stricture 31 HP:0002043
22 avascular necrosis 31 HP:0010885

Symptoms via clinical synopsis from OMIM:

56
Growth Height:
short stature

Respiratory Lung:
pulmonary fibrosis

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

Hematology:
pancytopenia
aplastic anemia
thrombocytopenia
leukopenia
bone marrow failure

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

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, Skin, Tongue

Publications for Dyskeratosis Congenita, Autosomal Dominant 2

Articles related to Dyskeratosis Congenita, Autosomal Dominant 2:

# Title Authors PMID Year
1
Expanding the clinical phenotype of autosomal dominant dyskeratosis congenita caused by TERT mutations. 56 6
18460650 2008
2
Complex inheritance pattern of dyskeratosis congenita in two families with 2 different mutations in the telomerase reverse transcriptase gene. 6 56
18042801 2008
3
Telomerase reverse-transcriptase homozygous mutations in autosomal recessive dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. 56 6
17785587 2007
4
Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita. 6 56
16247010 2005
5
Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells. 56
21602826 2011
6
Dyskeratosis Congenita 6
20301779 2009
7
Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. 6
15814878 2005

Variations for Dyskeratosis Congenita, Autosomal Dominant 2

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

6 (show top 50) (show all 544) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TERT NM_198253.2(TERT):c.2706G>C (p.Lys902Asn)SNV Pathogenic 12735 rs121918665 5:1264656-1264656 5:1264541-1264541
2 TERT NM_198253.2(TERT):c.1892G>A (p.Arg631Gln)SNV Pathogenic 29899 rs199422294 5:1280331-1280331 5:1280216-1280216
3 TERT NM_198253.2(TERT):c.2431C>T (p.Arg811Cys)SNV Pathogenic 29900 rs199422301 5:1271271-1271271 5:1271156-1271156
4 TERT NM_198253.2(TERT):c.2098C>T (p.Gln700Ter)SNV Pathogenic 242222 rs878855300 5:1279438-1279438 5:1279323-1279323
5 TERT NM_198253.2(TERT):c.336dup (p.Glu113fs)duplication Pathogenic 410651 rs1060502990 5:1294665-1294665 5:1294550-1294550
6 TERT NM_198253.2(TERT):c.2320C>T (p.Arg774Ter)SNV Pathogenic 446373 rs770066110 5:1272362-1272362 5:1272247-1272247
7 TERT NM_001193376.2(TERT):c.2919_2920CT[1] (p.Ile973_Ser974insTer)short repeat Pathogenic 539193 rs1554038257 5:1255448-1255449 5:1255333-1255334
8 TERT NM_198253.2(TERT):c.180G>A (p.Trp60Ter)SNV Pathogenic 568038 rs1554043139 5:1294925-1294925 5:1294810-1294810
9 TERT NM_001193376.2(TERT):c.1044_1045CT[2] (p.Leu350fs)short repeat Pathogenic 539192 rs1554042899 5:1293952-1293953 5:1293837-1293838
10 TERT NC_000005.9:g.(?_1280267)_(1280459_?)deldeletion Pathogenic 584005 5:1280267-1280459 5:1280152-1280344
11 TERT NM_198253.2(TERT):c.1685_1686del (p.Tyr562fs)deletion Pathogenic 664605 5:1282627-1282628 5:1282513-1282514
12 TERT NM_198253.2(TERT):c.1450G>T (p.Glu484Ter)SNV Pathogenic 656696 5:1293551-1293551 5:1293436-1293436
13 TERT NM_198253.2(TERT):c.688C>T (p.Arg230Ter)SNV Pathogenic 645232 5:1294313-1294313 5:1294198-1294198
14 TERT NC_000005.9:g.(?_1280263)_(1280463_?)deldeletion Pathogenic 654662 5:1280263-1280463 5:1280148-1280348
15 TERT NM_198253.2(TERT):c.2936G>A (p.Arg979Gln)SNV Conflicting interpretations of pathogenicity 506255 rs765566930 5:1260623-1260623 5:1260508-1260508
16 TERT NM_198253.2(TERT):c.2301A>G (p.Thr767=)SNV Conflicting interpretations of pathogenicity 436978 rs374592280 5:1272381-1272381 5:1272266-1272266
17 TERT NM_198253.2(TERT):c.2051A>G (p.Asp684Gly)SNV Conflicting interpretations of pathogenicity 446372 rs776981958 5:1279485-1279485 5:1279370-1279370
18 TERT NM_198253.2(TERT):c.2582+7C>ASNV Conflicting interpretations of pathogenicity 416309 rs766415474 5:1268628-1268628 5:1268513-1268513
19 TERT NM_198253.2(TERT):c.2130+10G>ASNV Conflicting interpretations of pathogenicity 416290 rs373879259 5:1279396-1279396 5:1279281-1279281
20 TERT NM_198253.2(TERT):c.663G>T (p.Ala221=)SNV Conflicting interpretations of pathogenicity 350803 rs35837567 5:1294338-1294338 5:1294223-1294223
21 TERT NM_198253.2(TERT):c.1269C>A (p.Ala423=)SNV Conflicting interpretations of pathogenicity 242213 rs190411812 5:1293732-1293732 5:1293617-1293617
22 TERT NM_198253.2(TERT):c.2455C>T (p.Arg819Cys)SNV Conflicting interpretations of pathogenicity 265268 rs746621306 5:1271247-1271247 5:1271132-1271132
23 TERT NM_198253.2(TERT):c.2654+10G>ASNV Conflicting interpretations of pathogenicity 350633 rs375473823 5:1266569-1266569 5:1266454-1266454
24 TERT NM_198253.2(TERT):c.3150G>C (p.Lys1050Asn)SNV Conflicting interpretations of pathogenicity 350518 rs373400596 5:1255409-1255409 5:1255294-1255294
25 TERT NM_198253.2(TERT):c.604G>A (p.Ala202Thr)SNV Conflicting interpretations of pathogenicity 12729 rs121918661 5:1294397-1294397 5:1294282-1294282
26 TERT NM_198253.2(TERT):c.2110C>T (p.Pro704Ser)SNV Conflicting interpretations of pathogenicity 39108 rs199422297 5:1279426-1279426 5:1279311-1279311
27 TERT NM_198253.2(TERT):c.3184G>A (p.Ala1062Thr)SNV Conflicting interpretations of pathogenicity 39121 rs35719940 5:1254594-1254594 5:1254479-1254479
28 TERT NM_198253.2(TERT):c.1990G>C (p.Val664Leu)SNV Conflicting interpretations of pathogenicity 212400 rs797046042 5:1279546-1279546 5:1279431-1279431
29 TERT NM_001193376.2(TERT):c.1317_1319GGA[2] (p.Glu441del)short repeat Conflicting interpretations of pathogenicity 212398 rs377639087 5:1293676-1293678 5:1293561-1293563
30 TERT NM_198253.2(TERT):c.2775C>T (p.His925=)SNV Conflicting interpretations of pathogenicity 242230 rs34528119 5:1264587-1264587 5:1264472-1264472
31 TERT NM_198253.2(TERT):c.2769G>A (p.Pro923=)SNV Conflicting interpretations of pathogenicity 242229 rs200174990 5:1264593-1264593 5:1264478-1264478
32 TERT NM_198253.2(TERT):c.3257G>A (p.Arg1086His)SNV Uncertain significance 242237 rs200288187 5:1254521-1254521 5:1254406-1254406
33 TERT NM_198253.2(TERT):c.3065A>T (p.His1022Leu)SNV Uncertain significance 242236 rs878855304 5:1255494-1255494 5:1255379-1255379
34 TERT NM_198253.2(TERT):c.3329C>T (p.Thr1110Met)SNV Uncertain significance 39122 rs199422306 5:1253913-1253913 5:1253798-1253798
35 TERT NM_198253.2(TERT):c.3268G>A (p.Val1090Met)SNV Uncertain significance 12733 rs121918664 5:1254510-1254510 5:1254395-1254395
36 TERT NM_198253.2(TERT):c.2935C>T (p.Arg979Trp)SNV Uncertain significance 39118 rs199422305 5:1260624-1260624 5:1260509-1260509
37 TERT NM_198253.2(TERT):c.2177C>T (p.Thr726Met)SNV Uncertain significance 39111 rs149566858 5:1278865-1278865 5:1278750-1278750
38 TERT NM_198253.2(TERT):c.2701C>T (p.Arg901Trp)SNV Uncertain significance 29901 rs199422304 5:1264661-1264661 5:1264546-1264546
39 TERT NM_198253.2(TERT):c.2371G>A (p.Val791Ile)SNV Uncertain significance 242228 rs141425941 5:1272311-1272311 5:1272196-1272196
40 TERT NM_198253.2(TERT):c.508G>A (p.Val170Met)SNV Uncertain significance 36947 rs387907248 5:1294493-1294493 5:1294378-1294378
41 TERT NM_001193376.2(TERT):c.887A>C (p.His296Pro)SNV Uncertain significance 268080 rs778187343 5:1294114-1294114 5:1293999-1293999
42 TERT NM_198253.2(TERT):c.150G>A (p.Leu50=)SNV Uncertain significance 289326 rs886044153 5:1294955-1294955 5:1294840-1294840
43 TERT NM_198253.2(TERT):c.2843+6C>TSNV Uncertain significance 242231 rs372086160 5:1264513-1264513 5:1264398-1264398
44 TERT NM_198253.2(TERT):c.-57A>CSNV Uncertain significance 242210 rs878855297 5:1295161-1295161 5:1295046-1295046
45 TERT NM_198253.2(TERT):c.1336C>A (p.Arg446Ser)SNV Uncertain significance 242216 rs567650961 5:1293665-1293665 5:1293550-1293550
46 TERT NM_198253.2(TERT):c.1331A>G (p.Asp444Gly)SNV Uncertain significance 242215 rs878855299 5:1293670-1293670 5:1293555-1293555
47 TERT NM_198253.2(TERT):c.1328C>G (p.Thr443Arg)SNV Uncertain significance 242214 rs772257175 5:1293673-1293673 5:1293558-1293558
48 TERT NM_198253.2(TERT):c.970G>A (p.Val324Met)SNV Uncertain significance 242247 rs878855307 5:1294031-1294031 5:1293916-1293916
49 TERT NM_198253.2(TERT):c.800A>G (p.Asp267Gly)SNV Uncertain significance 242244 rs878855306 5:1294201-1294201 5:1294086-1294086
50 TERT NM_198253.2(TERT):c.544A>T (p.Thr182Ser)SNV Uncertain significance 242243 rs878855305 5:1294457-1294457 5:1294342-1294342

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

73
# 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

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