DKCB1
MCID: DYS149
MIFTS: 39

Dyskeratosis Congenita, Autosomal Recessive 1 (DKCB1)

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 Recessive 1

MalaCards integrated aliases for Dyskeratosis Congenita, Autosomal Recessive 1:

Name: Dyskeratosis Congenita, Autosomal Recessive 1 57 13
Dkcb1 57 12 72
Dyskeratosis Congenita, Autosomal Recessive, 1 72 70
Dyskeratosis Congenita Autosomal Recessive 1 29 6
Dyskeratosis Congenita, Autosomal Recessive, Type 1 39
Autosomal Recessive Dyskeratosis Congenita 1 12

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype
classic triad consists of nail dystrophy, skin hyperpigmentation, and mucosal leukoplakia
median age of diagnosis - 15 years
mutation in nola3 found in 1 consanguineous saudi family (as of may 2011)


HPO:

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


Classifications:



Summaries for Dyskeratosis Congenita, Autosomal Recessive 1

OMIM® : 57 Dyskeratosis congenita is a bone marrow failure syndrome classically characterized by the triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa. Progressive bone marrow failure occurs in over 80% of cases and is the main cause of early mortality. The phenotype is highly variable, and affected individuals may have multiple additional features, including pulmonary fibrosis, liver cirrhosis, premature hair loss and/or graying, osteoporosis, atresia of the lacrimal ducts, and learning difficulties. Predisposition to malignancy is an important feature. The disorder is caused by defects in the maintenance of telomeres (summary by Kirwan and Dokal, 2008). For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (127550). (224230) (Updated 20-May-2021)

MalaCards based summary : Dyskeratosis Congenita, Autosomal Recessive 1, also known as dkcb1, is related to retinal telangiectasia and dyskeratosis congenita, autosomal recessive 2. An important gene associated with Dyskeratosis Congenita, Autosomal Recessive 1 is NOP10 (NOP10 Ribonucleoprotein), and among its related pathways/superpathways is Ribosome biogenesis in eukaryotes. Affiliated tissues include bone marrow, eye and skin, and related phenotypes are intellectual disability and carious teeth

Disease Ontology : 12 A dyskeratosis congenita that has material basis in an autosomal recessive mutation of NOLA3 on chromosome 15q14.

UniProtKB/Swiss-Prot : 72 Dyskeratosis congenita, autosomal recessive, 1: 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.

Related Diseases for Dyskeratosis Congenita, Autosomal Recessive 1

Graphical network of the top 20 diseases related to Dyskeratosis Congenita, Autosomal Recessive 1:



Diseases related to Dyskeratosis Congenita, Autosomal Recessive 1

Symptoms & Phenotypes for Dyskeratosis Congenita, Autosomal Recessive 1

Human phenotypes related to Dyskeratosis Congenita, Autosomal Recessive 1:

31 (show all 22)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 HP:0001249
2 carious teeth 31 HP:0000670
3 microcephaly 31 HP:0000252
4 microdontia 31 HP:0000691
5 osteoporosis 31 HP:0000939
6 hepatic fibrosis 31 HP:0001395
7 thrombocytopenia 31 HP:0001873
8 pulmonary fibrosis 31 HP:0002206
9 sparse scalp hair 31 HP:0002209
10 nasolacrimal duct obstruction 31 HP:0000579
11 nail dysplasia 31 HP:0002164
12 pterygium 31 HP:0001059
13 oral leukoplakia 31 HP:0002745
14 bone marrow hypocellularity 31 HP:0005528
15 nail dystrophy 31 HP:0008404
16 sparse eyelashes 31 HP:0000653
17 small nail 31 HP:0001792
18 esophageal stricture 31 HP:0002043
19 hyperpigmentation of the skin 31 HP:0000953
20 epiphora 31 HP:0009926
21 aplastic anemia 31 HP:0001915
22 pterygium of nails 31 HP:0002165

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Hematology:
thrombocytopenia
pancytopenia
aplastic anemia
bone marrow failure (classic feature, nola3 patient)

Head And Neck Head:
microcephaly (classic feature)

Skin Nails Hair Hair:
sparse eyelashes (classic feature)
sparse scalp hair (classic feature)

Head And Neck Teeth:
abnormal dentition (classic features, nola3 patient)
small teeth (classic feature)
dental caries (classic feature)

Abdomen Liver:
hepatic fibrosis (classic feature)

Skeletal:
osteoporosis (classic feature)

Neurologic:
learning difficulties (classic feature)
mental retardation (classic feature)

Laboratory Abnormalities:
shortened telomeres (classic feature, nola3 patient)

Skin Nails Hair Nails:
hypoplastic nails
longitudinal ridges
nail dystrophy (classic feature, nola3 patient)
pterygium formation

Head And Neck Eyes:
sparse eyelashes (classic feature)
epiphora (classic feature)
nasolacrimal duct obstruction (classic feature)

Head And Neck Mouth:
leukoplakia (classic feature)
purple tongue discoloration (classic feature)

Respiratory Lung:
pulmonary fibrosis (classic feature)

Abdomen Gastrointestinal:
esophageal stricture (classic feature)

Skin Nails Hair Skin:
reticular skin pigmentation (classic feature, nola3 patient)
thickening of the skin over the palms and soles (nola3 patient)

Neoplasia:
increased risk of malignancy (classic feature)

Clinical features from OMIM®:

224230 (Updated 20-May-2021)

Drugs & Therapeutics for Dyskeratosis Congenita, Autosomal Recessive 1

Search Clinical Trials , NIH Clinical Center for Dyskeratosis Congenita, Autosomal Recessive 1

Genetic Tests for Dyskeratosis Congenita, Autosomal Recessive 1

Genetic tests related to Dyskeratosis Congenita, Autosomal Recessive 1:

# Genetic test Affiliating Genes
1 Dyskeratosis Congenita Autosomal Recessive 1 29 NHP2 NOP10

Anatomical Context for Dyskeratosis Congenita, Autosomal Recessive 1

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

40
Bone Marrow, Eye, Skin, Bone, Tongue, T Cells

Publications for Dyskeratosis Congenita, Autosomal Recessive 1

Articles related to Dyskeratosis Congenita, Autosomal Recessive 1:

# Title Authors PMID Year
1
Genetic heterogeneity in autosomal recessive dyskeratosis congenita with one subtype due to mutations in the telomerase-associated protein NOP10. 57 6
17507419 2007
2
Dyskeratosis congenita: a genetic disorder of many faces. 57
18005359 2008
3
Dyskeratosis congenita: an autosomal recessive variant. 57
10096592 1999
4
Dyskeratosis congenita: clinical and genetic heterogeneity. Report of a new case and review of the literature. 57
1456394 1992
5
Etiologic heterogeneity in dyskeratosis congenita. 57
2705484 1989
6
Abnormality of platelet size and T-lymphocyte proliferation in an autosomal recessive form of dyskeratosis congenita. 57
3500870 1987
7
Active and suppressor T cells: diminution in a patient with dyskeratosis congenita and in first-degree relatives. 57
313356 1979
8
THE ASSOCIATION OF DYSKERATOSIS CONGENITA AND FANCONI'S ANAEMIA. 57
14312691 1965
9
DYSKERATOSIS CONGENITA. FIRST REPORT OF ITS OCCURRENCE IN A FEMALE AND A REVIEW OF THE LITERATURE. 57
14043629 1963

Variations for Dyskeratosis Congenita, Autosomal Recessive 1

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

6 (show all 41)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NOP10 NM_018648.3(NOP10):c.100C>T (p.Arg34Trp) SNV Pathogenic 4279 rs121908092 GRCh37: 15:34634264-34634264
GRCh38: 15:34342063-34342063
2 NOP10 NM_018648.3(NOP10):c.122_135delinsCACC (p.Tyr41fs) Indel Pathogenic 651009 rs1595604667 GRCh37: 15:34634229-34634242
GRCh38: 15:34342028-34342041
3 NHP2 , RMND5B NM_022762.5(RMND5B):c.*1767C>T SNV Pathogenic 4281 rs121908090 GRCh37: 5:177576800-177576800
GRCh38: 5:178149799-178149799
4 NHP2 , RMND5B NM_022762.5(RMND5B):c.*1728A>G SNV Pathogenic 4280 rs121908089 GRCh37: 5:177576761-177576761
GRCh38: 5:178149760-178149760
5 NHP2 , RMND5B NM_022762.5(RMND5B):c.*1683A>T SNV Pathogenic 4282 rs121908091 GRCh37: 5:177576716-177576716
GRCh38: 5:178149715-178149715
6 TERT NM_198253.2(TERT):c.2431C>T (p.Arg811Cys) SNV Pathogenic 29900 rs199422301 GRCh37: 5:1271271-1271271
GRCh38: 5:1271156-1271156
7 TERT NM_198253.2(TERT):c.2701C>T (p.Arg901Trp) SNV Pathogenic 29901 rs199422304 GRCh37: 5:1264661-1264661
GRCh38: 5:1264546-1264546
8 NOP10 NM_018648.3(NOP10):c.55-9C>T SNV Conflicting interpretations of pathogenicity 315637 rs72720799 GRCh37: 15:34634318-34634318
GRCh38: 15:34342117-34342117
9 NOP10 NM_018648.4(NOP10):c.*184A>G SNV Uncertain significance 886695 GRCh37: 15:34633985-34633985
GRCh38: 15:34341784-34341784
10 NOP10 NM_018648.4(NOP10):c.*132T>G SNV Uncertain significance 887949 GRCh37: 15:34634037-34634037
GRCh38: 15:34341836-34341836
11 NOP10 NM_018648.4(NOP10):c.*108T>C SNV Uncertain significance 887950 GRCh37: 15:34634061-34634061
GRCh38: 15:34341860-34341860
12 NOP10 NM_018648.4(NOP10):c.*80C>T SNV Uncertain significance 887951 GRCh37: 15:34634089-34634089
GRCh38: 15:34341888-34341888
13 NOP10 NM_018648.3(NOP10):c.27G>T (p.Glu9Asp) SNV Uncertain significance 644541 rs373678744 GRCh37: 15:34635248-34635248
GRCh38: 15:34343047-34343047
14 NOP10 NC_000015.10:g.34343161T>C SNV Uncertain significance 885736 GRCh37: 15:34635362-34635362
GRCh38: 15:34343161-34343161
15 NOP10 NC_000015.10:g.34343174G>C SNV Uncertain significance 885737 GRCh37: 15:34635375-34635375
GRCh38: 15:34343174-34343174
16 NOP10 NM_018648.3(NOP10):c.6del (p.Leu3fs) Deletion Uncertain significance 315639 rs756134994 GRCh37: 15:34635269-34635269
GRCh38: 15:34343068-34343068
17 NOP10 NM_018648.3(NOP10):c.179C>T (p.Pro60Leu) SNV Uncertain significance 466306 rs765367178 GRCh37: 15:34634185-34634185
GRCh38: 15:34341984-34341984
18 NOP10 NC_000015.10:g.(?_34341948)_(34343093_?)dup Duplication Uncertain significance 830917 GRCh37: 15:34634149-34635294
GRCh38:
19 NOP10 NM_018648.3(NOP10):c.-57C>T SNV Uncertain significance 315642 rs775092898 GRCh37: 15:34635331-34635331
GRCh38: 15:34343130-34343130
20 NOP10 NM_018648.3(NOP10):c.-38C>T SNV Uncertain significance 315640 rs112556317 GRCh37: 15:34635312-34635312
GRCh38: 15:34343111-34343111
21 NOP10 NM_018648.3(NOP10):c.*172T>G SNV Uncertain significance 315629 rs886051058 GRCh37: 15:34633997-34633997
GRCh38: 15:34341796-34341796
22 NOP10 NM_018648.3(NOP10):c.51G>C (p.Leu17=) SNV Uncertain significance 315638 rs761222362 GRCh37: 15:34635224-34635224
GRCh38: 15:34343023-34343023
23 NOP10 NM_018648.4(NOP10):c.31G>A (p.Gly11Arg) SNV Uncertain significance 1054213 GRCh37: 15:34635244-34635244
GRCh38: 15:34343043-34343043
24 NOP10 NM_018648.4(NOP10):c.156C>G (p.Phe52Leu) SNV Uncertain significance 1054241 GRCh37: 15:34634208-34634208
GRCh38: 15:34342007-34342007
25 NOP10 NM_018648.4(NOP10):c.92A>G (p.His31Arg) SNV Uncertain significance 1059000 GRCh37: 15:34634272-34634272
GRCh38: 15:34342071-34342071
26 NOP10 NM_018648.4(NOP10):c.89C>G (p.Ala30Gly) SNV Uncertain significance 857255 GRCh37: 15:34634275-34634275
GRCh38: 15:34342074-34342074
27 NOP10 NC_000015.9:g.(?_34634149)_(34635294_?)del Deletion Uncertain significance 1000345 GRCh37: 15:34634149-34635294
GRCh38:
28 NOP10 NM_018648.4(NOP10):c.89C>A (p.Ala30Asp) SNV Uncertain significance 1018359 GRCh37: 15:34634275-34634275
GRCh38: 15:34342074-34342074
29 NOP10 NM_018648.4(NOP10):c.141dup (p.Ile48fs) Duplication Uncertain significance 1036993 GRCh37: 15:34634222-34634223
GRCh38: 15:34342021-34342022
30 NOP10 NM_018648.4(NOP10):c.127C>G (p.Arg43Gly) SNV Uncertain significance 1047758 GRCh37: 15:34634237-34634237
GRCh38: 15:34342036-34342036
31 NOP10 NM_018648.3(NOP10):c.55-11T>C SNV Likely benign 436023 rs141981162 GRCh37: 15:34634320-34634320
GRCh38: 15:34342119-34342119
32 NOP10 NM_018648.4(NOP10):c.24C>T (p.Asn8=) SNV Likely benign 698096 rs756047969 GRCh37: 15:34635251-34635251
GRCh38: 15:34343050-34343050
33 NOP10 NM_018648.3(NOP10):c.34G>C (p.Asp12His) SNV Benign 235529 rs146261631 GRCh37: 15:34635241-34635241
GRCh38: 15:34343040-34343040
34 NOP10 NM_018648.3(NOP10):c.*31C>T SNV Benign 315635 rs1045204 GRCh37: 15:34634138-34634138
GRCh38: 15:34341937-34341937
35 NOP10 NM_018648.3(NOP10):c.*45G>C SNV Benign 315633 rs1045238 GRCh37: 15:34634124-34634124
GRCh38: 15:34341923-34341923
36 NOP10 NM_018648.3(NOP10):c.*30A>G SNV Benign 315636 rs1045194 GRCh37: 15:34634139-34634139
GRCh38: 15:34341938-34341938
37 NOP10 NM_018648.3(NOP10):c.55-10C>A SNV Benign 466307 rs200017156 GRCh37: 15:34634319-34634319
GRCh38: 15:34342118-34342118
38 NOP10 NM_018648.4(NOP10):c.55-15G>C SNV Benign 261036 rs422388 GRCh37: 15:34634324-34634324
GRCh38: 15:34342123-34342123
39 SLC12A6 , NOP10 NM_018648.3(NOP10):c.*149G>A SNV Benign 315630 rs7173 GRCh37: 15:34634020-34634020
GRCh38: 15:34341819-34341819
40 SLC12A6 , NOP10 NM_018648.3(NOP10):c.*136T>C SNV Benign 315631 rs3063 GRCh37: 15:34634033-34634033
GRCh38: 15:34341832-34341832
41 SLC12A6 , NOP10 NM_018648.3(NOP10):c.*129G>A SNV Benign 315632 rs115413508 GRCh37: 15:34634040-34634040
GRCh38: 15:34341839-34341839

UniProtKB/Swiss-Prot genetic disease variations for Dyskeratosis Congenita, Autosomal Recessive 1:

72
# Symbol AA change Variation ID SNP ID
1 NOP10 p.Arg34Trp VAR_043725 rs121908092

Expression for Dyskeratosis Congenita, Autosomal Recessive 1

Search GEO for disease gene expression data for Dyskeratosis Congenita, Autosomal Recessive 1.

Pathways for Dyskeratosis Congenita, Autosomal Recessive 1

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

# Super pathways Score Top Affiliating Genes
1 10.66 NOP10 NHP2

GO Terms for Dyskeratosis Congenita, Autosomal Recessive 1

Cellular components related to Dyskeratosis Congenita, Autosomal Recessive 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromosome, telomeric region GO:0000781 9.4 TERT NHP2
2 Cajal body GO:0015030 9.37 NOP10 NHP2
3 small nucleolar ribonucleoprotein complex GO:0005732 9.32 NOP10 NHP2
4 box H/ACA telomerase RNP complex GO:0090661 9.26 NOP10 NHP2
5 box H/ACA snoRNP complex GO:0031429 9.16 NOP10 NHP2
6 box H/ACA scaRNP complex GO:0072589 8.96 NOP10 NHP2
7 telomerase holoenzyme complex GO:0005697 8.8 TERT NOP10 NHP2

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

# Name GO ID Score Top Affiliating Genes
1 rRNA processing GO:0006364 9.37 NOP10 NHP2
2 ribosome biogenesis GO:0042254 9.32 NOP10 NHP2
3 positive regulation of telomerase RNA localization to Cajal body GO:1904874 9.26 NOP10 NHP2
4 rRNA pseudouridine synthesis GO:0031118 9.16 NOP10 NHP2
5 snRNA pseudouridine synthesis GO:0031120 8.96 NOP10 NHP2
6 telomere maintenance via telomerase GO:0007004 8.8 TERT NOP10 NHP2

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

# Name GO ID Score Top Affiliating Genes
1 box H/ACA snoRNA binding GO:0034513 8.96 NOP10 NHP2
2 telomerase RNA binding GO:0070034 8.8 TERT NOP10 NHP2

Sources for Dyskeratosis Congenita, Autosomal Recessive 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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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