DKCA2
MCID: DYS143
MIFTS: 30

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 57 13
Dyskeratosis Congenita, Autosomal Recessive, 4 75 29 6 73
Dyskeratosis Congenita, Autosomal Dominant, 2 75 29 6 73
Dkca2 57 12 75
Dkcb4 12 75
Dyskeratosis Congenita, Autosomal Dominant, Type 2 ) 40
Dyskeratosis Congenita, Autosomal Recessive 4 57
Autosomal Recessive Dyskeratosis Congenita 4 12
Autosomal Dominant Dyskeratosis Congenita 2 12
Dyskeratosis Congenita Scoggins Type 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive
autosomal dominant

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


HPO:

32
dyskeratosis congenita, autosomal dominant 2:
Inheritance genetic anticipation autosomal recessive inheritance autosomal dominant inheritance
Onset and clinical course phenotypic variability


Classifications:



Summaries for Dyskeratosis Congenita, Autosomal Dominant 2

UniProtKB/Swiss-Prot : 75 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, liver and bone marrow, 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)

Related Diseases for Dyskeratosis Congenita, Autosomal Dominant 2

Symptoms & Phenotypes for Dyskeratosis Congenita, Autosomal Dominant 2

Symptoms via clinical synopsis from OMIM:

57
Growth Height:
short stature

Respiratory Lung:
pulmonary fibrosis

Cardiovascular Heart:
dilated cardiomyopathy
cardiac fibrosis

Laboratory Abnormalities:
shortened telomeres
decreased telomerase activity

Abdomen Liver:
liver fibrosis

Head And Neck Head:
microcephaly (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

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 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

Human phenotypes related to Dyskeratosis Congenita, Autosomal Dominant 2:

32 (show all 22)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 global developmental delay 32 HP:0001263
3 aseptic necrosis 32 HP:0010885
4 abnormality of the dentition 32 HP:0000164
5 microcephaly 32 HP:0000252
6 short stature 32 HP:0004322
7 osteoporosis 32 HP:0000939
8 pulmonary fibrosis 32 HP:0002206
9 bone marrow hypocellularity 32 HP:0005528
10 aplastic anemia 32 HP:0001915
11 nail dystrophy 32 HP:0008404
12 thrombocytopenia 32 HP:0001873
13 dilated cardiomyopathy 32 HP:0001644
14 premature graying of hair 32 HP:0002216
15 cerebellar hypoplasia 32 HP:0001321
16 chronic diarrhea 32 HP:0002028
17 nail dysplasia 32 HP:0002164
18 leukopenia 32 HP:0001882
19 palmoplantar hyperkeratosis 32 HP:0000972
20 urethral stricture 32 HP:0012227
21 reticulated skin pigmentation 32 HP:0007427
22 esophageal stricture 32 HP:0002043

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:

41
Bone, Liver, Bone Marrow, Skin, Eye, Tongue

Publications for Dyskeratosis Congenita, Autosomal Dominant 2

Variations for Dyskeratosis Congenita, Autosomal Dominant 2

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

75
# 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
8 TERT p.Pro704Ser VAR_068793 rs199422297

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

6 (show top 50) (show all 879)
# Gene Variation Type Significance SNP ID Assembly Location
1 TERT NM_198253.2(TERT): c.604G> A (p.Ala202Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs121918661 GRCh37 Chromosome 5, 1294397: 1294397
2 TERT NM_198253.2(TERT): c.604G> A (p.Ala202Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs121918661 GRCh38 Chromosome 5, 1294282: 1294282
3 TERT NM_198253.2(TERT): c.1234C> T (p.His412Tyr) single nucleotide variant Conflicting interpretations of pathogenicity rs34094720 GRCh37 Chromosome 5, 1293767: 1293767
4 TERT NM_198253.2(TERT): c.1234C> T (p.His412Tyr) single nucleotide variant Conflicting interpretations of pathogenicity rs34094720 GRCh38 Chromosome 5, 1293652: 1293652
5 TERT NM_198253.2(TERT): c.3268G> A (p.Val1090Met) single nucleotide variant Uncertain significance rs121918664 GRCh37 Chromosome 5, 1254510: 1254510
6 TERT NM_198253.2(TERT): c.3268G> A (p.Val1090Met) single nucleotide variant Uncertain significance rs121918664 GRCh38 Chromosome 5, 1254395: 1254395
7 TERT NM_198253.2(TERT): c.2706G> C (p.Lys902Asn) single nucleotide variant Pathogenic rs121918665 GRCh37 Chromosome 5, 1264656: 1264656
8 TERT NM_198253.2(TERT): c.2706G> C (p.Lys902Asn) single nucleotide variant Pathogenic rs121918665 GRCh38 Chromosome 5, 1264541: 1264541
9 TERT NM_198253.2(TERT): c.1892G> A (p.Arg631Gln) single nucleotide variant Pathogenic rs199422294 GRCh37 Chromosome 5, 1280331: 1280331
10 TERT NM_198253.2(TERT): c.1892G> A (p.Arg631Gln) single nucleotide variant Pathogenic rs199422294 GRCh38 Chromosome 5, 1280216: 1280216
11 TERT NM_198253.2(TERT): c.2431C> T (p.Arg811Cys) single nucleotide variant Pathogenic rs199422301 GRCh37 Chromosome 5, 1271271: 1271271
12 TERT NM_198253.2(TERT): c.2431C> T (p.Arg811Cys) single nucleotide variant Pathogenic rs199422301 GRCh38 Chromosome 5, 1271156: 1271156
13 TERT NM_198253.2(TERT): c.2701C> T (p.Arg901Trp) single nucleotide variant Pathogenic rs199422304 GRCh37 Chromosome 5, 1264661: 1264661
14 TERT NM_198253.2(TERT): c.2701C> T (p.Arg901Trp) single nucleotide variant Pathogenic rs199422304 GRCh38 Chromosome 5, 1264546: 1264546
15 TERT NM_198253.2(TERT): c.2371G> A (p.Val791Ile) single nucleotide variant Uncertain significance rs141425941 GRCh37 Chromosome 5, 1272311: 1272311
16 TERT NM_198253.2(TERT): c.2371G> A (p.Val791Ile) single nucleotide variant Uncertain significance rs141425941 GRCh38 Chromosome 5, 1272196: 1272196
17 TERT NM_198253.2(TERT): c.508G> A (p.Val170Met) single nucleotide variant Uncertain significance rs387907248 GRCh37 Chromosome 5, 1294493: 1294493
18 TERT NM_198253.2(TERT): c.508G> A (p.Val170Met) single nucleotide variant Uncertain significance rs387907248 GRCh38 Chromosome 5, 1294378: 1294378
19 TERT NM_198253.2(TERT): c.2097C> T (p.Ala699=) single nucleotide variant Benign rs33963617 GRCh37 Chromosome 5, 1279439: 1279439
20 TERT NM_198253.2(TERT): c.2097C> T (p.Ala699=) single nucleotide variant Benign rs33963617 GRCh38 Chromosome 5, 1279324: 1279324
21 TERT NM_198253.2(TERT): c.2110C> T (p.Pro704Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs199422297 GRCh37 Chromosome 5, 1279426: 1279426
22 TERT NM_198253.2(TERT): c.2110C> T (p.Pro704Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs199422297 GRCh38 Chromosome 5, 1279311: 1279311
23 TERT NM_198253.2(TERT): c.2177C> T (p.Thr726Met) single nucleotide variant Uncertain significance rs149566858 GRCh37 Chromosome 5, 1278865: 1278865
24 TERT NM_198253.2(TERT): c.2177C> T (p.Thr726Met) single nucleotide variant Uncertain significance rs149566858 GRCh38 Chromosome 5, 1278750: 1278750
25 TERT NM_198253.2(TERT): c.2178G> A (p.Thr726=) single nucleotide variant Likely benign rs199422288 GRCh37 Chromosome 5, 1278864: 1278864
26 TERT NM_198253.2(TERT): c.2178G> A (p.Thr726=) single nucleotide variant Likely benign rs199422288 GRCh38 Chromosome 5, 1278749: 1278749
27 TERT NM_198253.2(TERT): c.2935C> T (p.Arg979Trp) single nucleotide variant Uncertain significance rs199422305 GRCh37 Chromosome 5, 1260624: 1260624
28 TERT NM_198253.2(TERT): c.2935C> T (p.Arg979Trp) single nucleotide variant Uncertain significance rs199422305 GRCh38 Chromosome 5, 1260509: 1260509
29 TERT NM_198253.2(TERT): c.3184G> A (p.Ala1062Thr) single nucleotide variant risk factor rs35719940 GRCh37 Chromosome 5, 1254594: 1254594
30 TERT NM_198253.2(TERT): c.3184G> A (p.Ala1062Thr) single nucleotide variant risk factor rs35719940 GRCh38 Chromosome 5, 1254479: 1254479
31 TERT NM_198253.2(TERT): c.3329C> T (p.Thr1110Met) single nucleotide variant Uncertain significance rs199422306 GRCh37 Chromosome 5, 1253913: 1253913
32 TERT NM_198253.2(TERT): c.3329C> T (p.Thr1110Met) single nucleotide variant Uncertain significance rs199422306 GRCh38 Chromosome 5, 1253798: 1253798
33 TERT NM_198253.2(TERT): c.835G> A (p.Ala279Thr) single nucleotide variant Benign rs61748181 GRCh37 Chromosome 5, 1294166: 1294166
34 TERT NM_198253.2(TERT): c.835G> A (p.Ala279Thr) single nucleotide variant Benign rs61748181 GRCh38 Chromosome 5, 1294051: 1294051
35 TERT NM_198253.2(TERT): c.3105C> T (p.Val1035=) single nucleotide variant Benign/Likely benign rs181612536 GRCh37 Chromosome 5, 1255454: 1255454
36 TERT NM_198253.2(TERT): c.3105C> T (p.Val1035=) single nucleotide variant Benign/Likely benign rs181612536 GRCh38 Chromosome 5, 1255339: 1255339
37 TERT NM_198253.2(TERT): c.1812A> G (p.Ala604=) single nucleotide variant Benign/Likely benign rs33959226 GRCh37 Chromosome 5, 1280411: 1280411
38 TERT NM_198253.2(TERT): c.1812A> G (p.Ala604=) single nucleotide variant Benign/Likely benign rs33959226 GRCh38 Chromosome 5, 1280296: 1280296
39 TERT NM_198253.2(TERT): c.3324G> A (p.Pro1108=) single nucleotide variant Benign rs35033501 GRCh37 Chromosome 5, 1253918: 1253918
40 TERT NM_198253.2(TERT): c.3324G> A (p.Pro1108=) single nucleotide variant Benign rs35033501 GRCh38 Chromosome 5, 1253803: 1253803
41 TERT NM_198253.2(TERT): c.3032+7C> T single nucleotide variant Likely benign rs371500615 GRCh37 Chromosome 5, 1258706: 1258706
42 TERT NM_198253.2(TERT): c.3032+7C> T single nucleotide variant Likely benign rs371500615 GRCh38 Chromosome 5, 1258591: 1258591
43 TERT NM_198253.2(TERT): c.969G> A (p.Pro323=) single nucleotide variant Benign rs148549782 GRCh37 Chromosome 5, 1294032: 1294032
44 TERT NM_198253.2(TERT): c.969G> A (p.Pro323=) single nucleotide variant Benign rs148549782 GRCh38 Chromosome 5, 1293917: 1293917
45 TERT NM_198253.2(TERT): c.1990G> C (p.Val664Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs797046042 GRCh38 Chromosome 5, 1279431: 1279431
46 TERT NM_198253.2(TERT): c.1990G> C (p.Val664Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs797046042 GRCh37 Chromosome 5, 1279546: 1279546
47 TERT NM_198253.2(TERT): c.1323_1325delGGA (p.Glu441del) deletion Conflicting interpretations of pathogenicity rs377639087 GRCh37 Chromosome 5, 1293676: 1293678
48 TERT NM_198253.2(TERT): c.1323_1325delGGA (p.Glu441del) deletion Conflicting interpretations of pathogenicity rs377639087 GRCh38 Chromosome 5, 1293561: 1293563
49 TERT NM_198253.2(TERT): c.1951-205G> A single nucleotide variant Benign rs10069690 GRCh38 Chromosome 5, 1279675: 1279675
50 TERT NM_198253.2(TERT): c.1951-205G> A single nucleotide variant Benign rs10069690 GRCh37 Chromosome 5, 1279790: 1279790

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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