MCID: DYS149
MIFTS: 35

Dyskeratosis Congenita, Autosomal Recessive 1

Categories: Genetic diseases, Skin diseases, Blood diseases, Rare diseases, Neuronal diseases, Eye diseases, Fetal diseases, Immune 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 75
Dyskeratosis Congenita, Autosomal Recessive, 1 75 73
Dyskeratosis Congenita Autosomal Recessive 1 29 6
Dyskeratosis Congenita, Autosomal Recessive, Type 1 40
Autosomal Recessive Dyskeratosis Congenita 1 12

Characteristics:

OMIM:

57
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:

32
dyskeratosis congenita, autosomal recessive 1:
Onset and clinical course phenotypic variability
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)

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

UniProtKB/Swiss-Prot : 75 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.

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

Related Diseases for Dyskeratosis Congenita, Autosomal Recessive 1

Symptoms & Phenotypes for Dyskeratosis Congenita, Autosomal Recessive 1

Symptoms via clinical synopsis from OMIM:

57
Hematology:
pancytopenia
aplastic anemia
thrombocytopenia
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
nail dystrophy (classic feature, nola3 patient)
longitudinal ridges
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

Human phenotypes related to Dyskeratosis Congenita, Autosomal Recessive 1:

32 (show all 21)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 32 HP:0001249
2 carious teeth 32 HP:0000670
3 microcephaly 32 HP:0000252
4 osteoporosis 32 HP:0000939
5 pulmonary fibrosis 32 HP:0002206
6 bone marrow hypocellularity 32 HP:0005528
7 aplastic anemia 32 HP:0001915
8 nail dystrophy 32 HP:0008404
9 microdontia 32 HP:0000691
10 hepatic fibrosis 32 HP:0001395
11 thrombocytopenia 32 HP:0001873
12 small nail 32 HP:0001792
13 sparse scalp hair 32 HP:0002209
14 nasolacrimal duct obstruction 32 HP:0000579
15 nail dysplasia 32 HP:0002164
16 oral leukoplakia 32 HP:0002745
17 sparse eyelashes 32 HP:0000653
18 hyperpigmentation of the skin 32 HP:0000953
19 esophageal stricture 32 HP:0002043
20 epiphora 32 HP:0009926
21 pterygium of nails 32 HP:0002165

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:

41
Skin, Bone, Bone Marrow, Liver, Tongue

Publications for Dyskeratosis Congenita, Autosomal Recessive 1

Variations for Dyskeratosis Congenita, Autosomal Recessive 1

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

75
# Symbol AA change Variation ID SNP ID
1 NOP10 p.Arg34Trp VAR_043725 rs121908092

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

6
(show all 20)
# Gene Variation Type Significance SNP ID Assembly Location
1 NOP10 NM_018648.3(NOP10): c.100C> T (p.Arg34Trp) single nucleotide variant Pathogenic rs121908092 GRCh37 Chromosome 15, 34634264: 34634264
2 NOP10 NM_018648.3(NOP10): c.100C> T (p.Arg34Trp) single nucleotide variant Pathogenic rs121908092 GRCh38 Chromosome 15, 34342063: 34342063
3 NHP2 NM_017838.3(NHP2): c.415T> C (p.Tyr139His) single nucleotide variant Pathogenic rs121908089 GRCh37 Chromosome 5, 177576761: 177576761
4 NHP2 NM_017838.3(NHP2): c.415T> C (p.Tyr139His) single nucleotide variant Pathogenic rs121908089 GRCh38 Chromosome 5, 178149760: 178149760
5 NHP2 NM_017838.3(NHP2): c.376G> A (p.Val126Met) single nucleotide variant Pathogenic rs121908090 GRCh37 Chromosome 5, 177576800: 177576800
6 NHP2 NM_017838.3(NHP2): c.376G> A (p.Val126Met) single nucleotide variant Pathogenic rs121908090 GRCh38 Chromosome 5, 178149799: 178149799
7 NHP2 NM_017838.3(NHP2): c.460T> A (p.Ter154Arg) single nucleotide variant Pathogenic rs121908091 GRCh37 Chromosome 5, 177576716: 177576716
8 NHP2 NM_017838.3(NHP2): c.460T> A (p.Ter154Arg) single nucleotide variant Pathogenic rs121908091 GRCh38 Chromosome 5, 178149715: 178149715
9 TERT NM_198253.2(TERT): c.2431C> T (p.Arg811Cys) single nucleotide variant Pathogenic rs199422301 GRCh37 Chromosome 5, 1271271: 1271271
10 TERT NM_198253.2(TERT): c.2431C> T (p.Arg811Cys) single nucleotide variant Pathogenic rs199422301 GRCh38 Chromosome 5, 1271156: 1271156
11 TERT NM_198253.2(TERT): c.2701C> T (p.Arg901Trp) single nucleotide variant Pathogenic rs199422304 GRCh37 Chromosome 5, 1264661: 1264661
12 TERT NM_198253.2(TERT): c.2701C> T (p.Arg901Trp) single nucleotide variant Pathogenic rs199422304 GRCh38 Chromosome 5, 1264546: 1264546
13 NOP10 NM_018648.3(NOP10): c.34G> C (p.Asp12His) single nucleotide variant Benign/Likely benign rs146261631 GRCh37 Chromosome 15, 34635241: 34635241
14 NOP10 NM_018648.3(NOP10): c.34G> C (p.Asp12His) single nucleotide variant Benign/Likely benign rs146261631 GRCh38 Chromosome 15, 34343040: 34343040
15 NOP10 NM_018648.3(NOP10): c.55-9C> T single nucleotide variant Conflicting interpretations of pathogenicity rs72720799 GRCh38 Chromosome 15, 34342117: 34342117
16 NOP10 NM_018648.3(NOP10): c.55-9C> T single nucleotide variant Conflicting interpretations of pathogenicity rs72720799 GRCh37 Chromosome 15, 34634318: 34634318
17 NOP10 NM_018648.3(NOP10): c.55-10C> A single nucleotide variant Benign rs200017156 GRCh38 Chromosome 15, 34342118: 34342118
18 NOP10 NM_018648.3(NOP10): c.55-10C> A single nucleotide variant Benign rs200017156 GRCh37 Chromosome 15, 34634319: 34634319
19 NOP10 NM_018648.3(NOP10): c.179C> T (p.Pro60Leu) single nucleotide variant Uncertain significance rs765367178 GRCh38 Chromosome 15, 34341984: 34341984
20 NOP10 NM_018648.3(NOP10): c.179C> T (p.Pro60Leu) single nucleotide variant Uncertain significance rs765367178 GRCh37 Chromosome 15, 34634185: 34634185

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
Show member pathways
11.49 NHP2 TERT
2 10.64 NHP2 NOP10

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 nucleolus GO:0005730 9.61 NHP2 NOP10 TERT
2 nuclear chromosome, telomeric region GO:0000784 9.4 NHP2 TERT
3 Cajal body GO:0015030 9.37 NHP2 NOP10
4 small nucleolar ribonucleoprotein complex GO:0005732 9.32 NHP2 NOP10
5 box H/ACA snoRNP complex GO:0031429 9.26 NHP2 NOP10
6 box H/ACA telomerase RNP complex GO:0090661 9.16 NHP2 NOP10
7 box H/ACA scaRNP complex GO:0072589 8.96 NHP2 NOP10
8 telomerase holoenzyme complex GO:0005697 8.8 NHP2 NOP10 TERT

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 NHP2 NOP10
2 ribosome biogenesis GO:0042254 9.32 NHP2 NOP10
3 positive regulation of telomerase RNA localization to Cajal body GO:1904874 9.26 NHP2 NOP10
4 rRNA pseudouridine synthesis GO:0031118 9.16 NHP2 NOP10
5 snRNA pseudouridine synthesis GO:0031120 8.96 NHP2 NOP10
6 telomere maintenance via telomerase GO:0007004 8.8 NHP2 NOP10 TERT

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

# Name GO ID Score Top Affiliating Genes
1 RNA binding GO:0003723 9.43 NHP2 NOP10 TERT
2 snoRNA binding GO:0030515 9.16 NHP2 NOP10
3 box H/ACA snoRNA binding GO:0034513 8.96 NHP2 NOP10
4 telomerase RNA binding GO:0070034 8.8 NHP2 NOP10 TERT

Sources for Dyskeratosis Congenita, Autosomal Recessive 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
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50 NCIt
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55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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