DKCA6
MCID: DYS174
MIFTS: 37

Dyskeratosis Congenita, Autosomal Dominant 6 (DKCA6)

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 6

MalaCards integrated aliases for Dyskeratosis Congenita, Autosomal Dominant 6:

Name: Dyskeratosis Congenita, Autosomal Dominant 6 57 29 6
Dyskeratosis Congenita, Autosomal Recessive 7 57 29 6
Dkca6 57 12 72
Dyskeratosis Congenita, Autosomal Recessive, 7 72
Dyskeratosis Congenita, Autosomal Dominant, 6 72
Autosomal Dominant Dyskeratosis Congenita 6 12
Hereditary Isolated Aplastic Anemia 58
Dkcb7 72

Characteristics:

Orphanet epidemiological data:

58
hereditary isolated aplastic anemia
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
two unrelated families have been reported (last curated september 2015)
one family with autosomal dominant inheritance had only progressive bone marrow failure
one patient (patient b) with autosomal recessive inheritance had a more severe phenotype


HPO:

31
dyskeratosis congenita, autosomal dominant 6:
Inheritance autosomal dominant inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare haematological diseases


External Ids:

Disease Ontology 12 DOID:0070023
OMIM® 57 616553
OMIM Phenotypic Series 57 PS127550
MeSH 44 D019871
ICD10 via Orphanet 33 D61.0
Orphanet 58 ORPHA397692

Summaries for Dyskeratosis Congenita, Autosomal Dominant 6

UniProtKB/Swiss-Prot : 72 Dyskeratosis congenita, autosomal dominant, 6: A 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.
Dyskeratosis congenita, autosomal recessive, 7: A 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 6, also known as dyskeratosis congenita, autosomal recessive 7, is related to thrombocytopenia 3 and acquired thrombocytopenia. An important gene associated with Dyskeratosis Congenita, Autosomal Dominant 6 is ACD (ACD Shelterin Complex Subunit And Telomerase Recruitment Factor), and among its related pathways/superpathways are JAK-STAT signaling pathway and Visual Cycle in Retinal Rods. Affiliated tissues include bone marrow, bone and liver, and related phenotypes are abnormality of the dentition and global developmental delay

Disease Ontology : 12 A dyskeratosis congenita that has material basis in an autosomal dominant mutation of ACD on chromosome 16q22.1.

OMIM® : 57 Dyskeratosis congenita is a multisystem disorder caused by defective telomere maintenance. Features are variable and include bone marrow failure, nail dysplasia, oral leukoplakia, and increased risk of cancer (summary by Kocak et al., 2014). For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (127550). (616553) (Updated 05-Apr-2021)

Related Diseases for Dyskeratosis Congenita, Autosomal Dominant 6

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 6 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 33)
# Related Disease Score Top Affiliating Genes
1 thrombocytopenia 3 9.9 THPO MPL
2 acquired thrombocytopenia 9.9 THPO MPL
3 splenic sequestration 9.8 THPO MPL
4 thrombocythemia 1 9.8 THPO MPL
5 evans' syndrome 9.8 THPO MPL
6 amegakaryocytic thrombocytopenia, congenital 9.8 THPO MPL
7 primary thrombocytopenia 9.8 THPO MPL
8 thrombocytopenia-absent radius syndrome 9.8 THPO MPL
9 thrombocytopenia due to platelet alloimmunization 9.8 THPO MPL
10 autoimmune disease of blood 9.8 THPO MPL
11 thrombocytopenic purpura, autoimmune 9.8 THPO MPL
12 purpura 9.8 THPO MPL
13 myeloproliferative syndrome, transient 9.8 THPO MPL
14 thrombocytosis 9.8 THPO MPL
15 bernard-soulier syndrome 9.8 THPO MPL
16 paroxysmal nocturnal hemoglobinuria 9.8 THPO MPL
17 acute megakaryocytic leukemia 9.8 THPO MPL
18 polycythemia 9.8 THPO MPL
19 blood platelet disease 9.8 THPO MPL
20 blood coagulation disease 9.8 THPO MPL
21 pancytopenia 9.8 THPO MPL
22 bone marrow cancer 9.8 THPO MPL
23 polycythemia vera 9.8 THPO MPL
24 essential thrombocythemia 9.8 THPO MPL
25 myeloproliferative neoplasm 9.7 THPO MPL
26 hemorrhagic disease 9.7 THPO MPL
27 neutropenia 9.7 THPO MPL
28 acute leukemia 9.7 THPO MPL
29 myelofibrosis 9.7 THPO MPL
30 hematologic cancer 9.6 THPO MPL
31 diamond-blackfan anemia 9.6 THPO MPL
32 aplastic anemia 9.5 THPO MPL ACD
33 leukemia, chronic myeloid 9.5 THPO MPL

Graphical network of the top 20 diseases related to Dyskeratosis Congenita, Autosomal Dominant 6:



Diseases related to Dyskeratosis Congenita, Autosomal Dominant 6

Symptoms & Phenotypes for Dyskeratosis Congenita, Autosomal Dominant 6

Human phenotypes related to Dyskeratosis Congenita, Autosomal Dominant 6:

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 abnormality of the dentition 31 occasional (7.5%) HP:0000164
2 global developmental delay 31 HP:0001263
3 microcephaly 31 HP:0000252
4 intrauterine growth retardation 31 HP:0001511
5 cerebellar hypoplasia 31 HP:0001321
6 oral leukoplakia 31 HP:0002745
7 bone marrow hypocellularity 31 HP:0005528
8 nail dystrophy 31 HP:0008404
9 esophageal stenosis 31 HP:0010450
10 aplastic anemia 31 HP:0001915

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Hematology:
pancytopenia
aplastic anemia
bone marrow failure, progressive

Neoplasia:
increased susceptibility to cancer

Growth Other:
intrauterine growth retardation (patient b)

Head And Neck Mouth:
oral leukoplakia (patient b)

Skin Nails Hair Nails:
nail dystrophy (patient b)

Neurologic Central Nervous System:
delayed development (patient b)
cerebellar hypoplasia (patient b)

Laboratory Abnormalities:
shortened telomeres

Head And Neck Teeth:
dental abnormalities (in some patients)

Head And Neck Head:
microcephaly (patient b)

Abdomen Gastrointestinal:
esophageal stenosis (patient b)

Skin Nails Hair Hair:
premature gray hair (in some patients)

Clinical features from OMIM®:

616553 (Updated 05-Apr-2021)

Drugs & Therapeutics for Dyskeratosis Congenita, Autosomal Dominant 6

Search Clinical Trials , NIH Clinical Center for Dyskeratosis Congenita, Autosomal Dominant 6

Genetic Tests for Dyskeratosis Congenita, Autosomal Dominant 6

Genetic tests related to Dyskeratosis Congenita, Autosomal Dominant 6:

# Genetic test Affiliating Genes
1 Dyskeratosis Congenita, Autosomal Dominant 6 29 ACD
2 Dyskeratosis Congenita, Autosomal Recessive 7 29

Anatomical Context for Dyskeratosis Congenita, Autosomal Dominant 6

MalaCards organs/tissues related to Dyskeratosis Congenita, Autosomal Dominant 6:

40
Bone Marrow, Bone, Liver

Publications for Dyskeratosis Congenita, Autosomal Dominant 6

Articles related to Dyskeratosis Congenita, Autosomal Dominant 6:

# Title Authors PMID Year
1
Inherited bone marrow failure associated with germline mutation of ACD, the gene encoding telomere protein TPP1. 6 57
25205116 2014
2
Hoyeraal-Hreidarsson syndrome caused by a germline mutation in the TEL patch of the telomere protein TPP1. 57 6
25233904 2014

Variations for Dyskeratosis Congenita, Autosomal Dominant 6

ClinVar genetic disease variations for Dyskeratosis Congenita, Autosomal Dominant 6:

6 (show top 50) (show all 109)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ACD NM_001082486.2(ACD):c.545del (p.Gln182fs) Deletion Pathogenic 1033277 GRCh37: 16:67692931-67692931
GRCh38: 16:67659028-67659028
2 ACD NM_001082486.2(ACD):c.250_252del (p.Lys84del) Deletion Pathogenic 208983 rs797045144 GRCh37: 16:67693689-67693691
GRCh38: 16:67659786-67659788
3 ACD NM_001082486.2(ACD):c.250_252del (p.Lys84del) Deletion Pathogenic 208983 rs797045144 GRCh37: 16:67693689-67693691
GRCh38: 16:67659786-67659788
4 ACD NM_001082486.2(ACD):c.1213C>A (p.Pro405Thr) SNV Pathogenic 208984 rs201441120 GRCh37: 16:67691750-67691750
GRCh38: 16:67657847-67657847
5 ACD NG_042874.1(ACD)::g.5474del Deletion Conflicting interpretations of pathogenicity 542415 rs753666055 GRCh37: 16:67694245-67694245
GRCh38: 16:67660342-67660342
6 ACD NM_001082486.2(ACD):c.1306C>T (p.Pro436Ser) SNV Uncertain significance 542416 rs201926842 GRCh37: 16:67691580-67691580
GRCh38: 16:67657677-67657677
7 ACD NM_001082486.2(ACD):c.737C>A (p.Thr246Lys) SNV Uncertain significance 542417 rs1555542235 GRCh37: 16:67692628-67692628
GRCh38: 16:67658725-67658725
8 ACD NM_001082486.2(ACD):c.683G>A (p.Cys228Tyr) SNV Uncertain significance 1035262 GRCh37: 16:67692682-67692682
GRCh38: 16:67658779-67658779
9 ACD NM_001082486.2(ACD):c.18G>T (p.Arg6Ser) SNV Uncertain significance 1036684 GRCh37: 16:67694106-67694106
GRCh38: 16:67660203-67660203
10 ACD NM_001082486.2(ACD):c.799G>T (p.Ala267Ser) SNV Uncertain significance 1038926 GRCh37: 16:67692488-67692488
GRCh38: 16:67658585-67658585
11 ACD NM_001082486.2(ACD):c.1186C>T (p.Gln396Ter) SNV Uncertain significance 1040312 GRCh37: 16:67691909-67691909
GRCh38: 16:67658006-67658006
12 ACD NM_001082486.2(ACD):c.608_609del (p.Pro203fs) Deletion Uncertain significance 1041332 GRCh37: 16:67692867-67692868
GRCh38: 16:67658964-67658965
13 ACD NM_001082486.2(ACD):c.743-7C>A SNV Uncertain significance 1041334 GRCh37: 16:67692551-67692551
GRCh38: 16:67658648-67658648
14 ACD NC_000016.9:g.67694362C>G SNV Uncertain significance 1044004 GRCh37: 16:67694362-67694362
GRCh38: 16:67660459-67660459
15 ACD NC_000016.9:g.67694300_67694301insCCCGCTGGTCCAC Duplication Uncertain significance 1045472 GRCh37: 16:67694300-67694301
GRCh38: 16:67660397-67660398
16 ACD NC_000016.9:g.67694174C>T SNV Uncertain significance 1045596 GRCh37: 16:67694174-67694174
GRCh38: 16:67660271-67660271
17 ACD NC_000016.9:g.67694305C>G SNV Uncertain significance 1047168 GRCh37: 16:67694305-67694305
GRCh38: 16:67660402-67660402
18 ACD NM_001082486.2(ACD):c.741G>C (p.Gln247His) SNV Uncertain significance 567408 rs776468683 GRCh37: 16:67692624-67692624
GRCh38: 16:67658721-67658721
19 ACD NM_001082486.2(ACD):c.1025A>G (p.Gln342Arg) SNV Uncertain significance 568882 rs1567640107 GRCh37: 16:67692070-67692070
GRCh38: 16:67658167-67658167
20 ACD NM_001082486.2(ACD):c.974C>T (p.Thr325Ile) SNV Uncertain significance 572279 rs777812658 GRCh37: 16:67692121-67692121
GRCh38: 16:67658218-67658218
21 ACD NM_001082486.2(ACD):c.809C>T (p.Pro270Leu) SNV Uncertain significance 572998 rs1035052101 GRCh37: 16:67692478-67692478
GRCh38: 16:67658575-67658575
22 ACD NM_001082486.2(ACD):c.644C>T (p.Thr215Met) SNV Uncertain significance 575039 rs72547495 GRCh37: 16:67692832-67692832
GRCh38: 16:67658929-67658929
23 ACD NM_001082486.2(ACD):c.-188_-187inv (p.Trp24Ser) Inversion Uncertain significance 575071 GRCh37: 16:67694310-67694311
GRCh38: 16:67660407-67660408
24 ACD NM_001082486.2(ACD):c.997G>A (p.Ala333Thr) SNV Uncertain significance 434067 rs202104741 GRCh37: 16:67692098-67692098
GRCh38: 16:67658195-67658195
25 ACD NM_001082486.2(ACD):c.739C>A (p.Gln247Lys) SNV Uncertain significance 642162 rs1597770431 GRCh37: 16:67692626-67692626
GRCh38: 16:67658723-67658723
26 ACD NM_001082486.2(ACD):c.781C>G (p.Leu261Val) SNV Uncertain significance 643676 rs760404492 GRCh37: 16:67692506-67692506
GRCh38: 16:67658603-67658603
27 ACD NM_001082486.2(ACD):c.645G>A (p.Thr215=) SNV Uncertain significance 648536 rs571116752 GRCh37: 16:67692831-67692831
GRCh38: 16:67658928-67658928
28 ACD NM_001082486.2(ACD):c.734G>A (p.Arg245Lys) SNV Uncertain significance 649693 rs1048865744 GRCh37: 16:67692631-67692631
GRCh38: 16:67658728-67658728
29 ACD NM_001082486.2(ACD):c.1178G>A (p.Arg393Lys) SNV Uncertain significance 653471 rs531580930 GRCh37: 16:67691917-67691917
GRCh38: 16:67658014-67658014
30 ACD NM_001082486.2(ACD):c.350A>G (p.Tyr117Cys) SNV Uncertain significance 657744 rs775602659 GRCh37: 16:67693503-67693503
GRCh38: 16:67659600-67659600
31 ACD NM_001082486.2(ACD):c.830-1G>A SNV Uncertain significance 665605 rs1597769397 GRCh37: 16:67692266-67692266
GRCh38: 16:67658363-67658363
32 ACD NM_001082486.2(ACD):c.343G>C (p.Glu115Gln) SNV Uncertain significance 838956 GRCh37: 16:67693510-67693510
GRCh38: 16:67659607-67659607
33 ACD NM_001082486.2(ACD):c.793C>G (p.Leu265Val) SNV Uncertain significance 848065 GRCh37: 16:67692494-67692494
GRCh38: 16:67658591-67658591
34 ACD NG_042874.1:g.5456C>T SNV Uncertain significance 849856 GRCh37: 16:67694263-67694263
GRCh38: 16:67660360-67660360
35 ACD NM_001082486.2(ACD):c.1063C>T (p.Pro355Ser) SNV Uncertain significance 860243 GRCh37: 16:67692032-67692032
GRCh38: 16:67658129-67658129
36 ACD NM_001082486.2(ACD):c.590G>T (p.Gly197Val) SNV Uncertain significance 861384 GRCh37: 16:67692886-67692886
GRCh38: 16:67658983-67658983
37 ACD NM_001082486.2(ACD):c.602C>T (p.Ala201Val) SNV Uncertain significance 862640 GRCh37: 16:67692874-67692874
GRCh38: 16:67658971-67658971
38 ACD NM_001082486.2(ACD):c.527G>T (p.Arg176Leu) SNV Uncertain significance 863083 GRCh37: 16:67692949-67692949
GRCh38: 16:67659046-67659046
39 ACD NM_001082486.2(ACD):c.1052G>A (p.Arg351His) SNV Uncertain significance 937272 GRCh37: 16:67692043-67692043
GRCh38: 16:67658140-67658140
40 ACD NG_042874.1:g.5406_5418del Deletion Uncertain significance 964834 GRCh37: 16:67694301-67694313
GRCh38: 16:67660398-67660410
41 ACD NM_001082486.1(ACD):c.179T>G (p.Leu60Arg) SNV Uncertain significance 432482 rs753367228 GRCh37: 16:67694203-67694203
GRCh38: 16:67660300-67660300
42 ACD NM_001082486.2(ACD):c.100G>A (p.Val34Ile) SNV Uncertain significance 973878 GRCh37: 16:67693948-67693948
GRCh38: 16:67660045-67660045
43 ACD NM_001082486.2(ACD):c.399_400insAAG (p.Arg134_Val135insLys) Insertion Uncertain significance 835919 GRCh37: 16:67693453-67693454
GRCh38: 16:67659550-67659551
44 ACD NM_001082486.2(ACD):c.1148G>A (p.Arg383Gln) SNV Uncertain significance 838233 GRCh37: 16:67691947-67691947
GRCh38: 16:67658044-67658044
45 ACD NM_001082486.2(ACD):c.488A>G (p.Asn163Ser) SNV Uncertain significance 858372 GRCh37: 16:67693137-67693137
GRCh38: 16:67659234-67659234
46 ACD NM_001082486.2(ACD):c.-9G>T SNV Uncertain significance 860923 GRCh37: 16:67694132-67694132
GRCh38: 16:67660229-67660229
47 ACD NM_001082486.2(ACD):c.817_828del (p.Pro273_Ser276del) Deletion Uncertain significance 933916 GRCh37: 16:67692459-67692470
GRCh38: 16:67658556-67658567
48 ACD NM_001082486.2(ACD):c.608C>T (p.Pro203Leu) SNV Uncertain significance 944166 GRCh37: 16:67692868-67692868
GRCh38: 16:67658965-67658965
49 ACD NM_001082486.2(ACD):c.1334T>C (p.Phe445Ser) SNV Uncertain significance 946723 GRCh37: 16:67691552-67691552
GRCh38: 16:67657649-67657649
50 ACD NM_001082486.2(ACD):c.-20C>T SNV Uncertain significance 963062 GRCh37: 16:67694143-67694143
GRCh38: 16:67660240-67660240

UniProtKB/Swiss-Prot genetic disease variations for Dyskeratosis Congenita, Autosomal Dominant 6:

72
# Symbol AA change Variation ID SNP ID
1 ACD p.Pro405Thr VAR_075694 rs201441120

Expression for Dyskeratosis Congenita, Autosomal Dominant 6

Search GEO for disease gene expression data for Dyskeratosis Congenita, Autosomal Dominant 6.

Pathways for Dyskeratosis Congenita, Autosomal Dominant 6

GO Terms for Dyskeratosis Congenita, Autosomal Dominant 6

Biological processes related to Dyskeratosis Congenita, Autosomal Dominant 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 thrombopoietin-mediated signaling pathway GO:0038163 8.62 THPO MPL

Sources for Dyskeratosis Congenita, Autosomal Dominant 6

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