MCID: DYS149
MIFTS: 35

Dyskeratosis Congenita, Autosomal Recessive 1

Categories: Genetic diseases, Rare diseases, Skin diseases, Blood diseases, Fetal diseases, Eye diseases, Neuronal 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 53 13
Dyskeratosis Congenita, Autosomal Recessive, 1 71 69
Dkcb1 53 71
Dyskeratosis Congenita Autosomal Recessive 1 28

Characteristics:

OMIM:

53
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:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Dyskeratosis Congenita, Autosomal Recessive 1

OMIM : 53 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 dyskeratosis congenita, autosomal recessive, 1, is related to pulmonary fibrosis, idiopathic and dyskeratosis congenita autosomal recessive, and has symptoms including intellectual disability, carious teeth and microcephaly. 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.

UniProtKB/Swiss-Prot : 71 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

Symptoms & Phenotypes for Dyskeratosis Congenita, Autosomal Recessive 1

Symptoms via clinical synopsis from OMIM:

53
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 Gastroin testinal:
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:

31 (show all 21)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 HP:0001249
2 carious teeth 31 HP:0000670
3 microcephaly 31 HP:0000252
4 osteoporosis 31 HP:0000939
5 pulmonary fibrosis 31 HP:0002206
6 bone marrow hypocellularity 31 HP:0005528
7 aplastic anemia 31 HP:0001915
8 nail dystrophy 31 HP:0008404
9 microdontia 31 HP:0000691
10 hepatic fibrosis 31 HP:0001395
11 thrombocytopenia 31 HP:0001873
12 small nail 31 HP:0001792
13 sparse scalp hair 31 HP:0002209
14 nasolacrimal duct obstruction 31 HP:0000579
15 nail dysplasia 31 HP:0002164
16 oral leukoplakia 31 HP:0002745
17 sparse eyelashes 31 HP:0000653
18 hyperpigmentation of the skin 31 HP:0000953
19 esophageal stricture 31 HP:0002043
20 epiphora 31 HP:0009926
21 pterygium of nails 31 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 28 NHP2 NOP10

Anatomical Context for Dyskeratosis Congenita, Autosomal Recessive 1

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

38
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:

71
# 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
# Gene Variation Type Significance SNP ID Assembly Location
1 TERT NM_198253.2(TERT): c.2431C> T (p.Arg811Cys) single nucleotide variant Pathogenic rs199422301 GRCh37 Chromosome 5, 1271271: 1271271
2 TERT NM_198253.2(TERT): c.2701C> T (p.Arg901Trp) single nucleotide variant Pathogenic rs199422304 GRCh37 Chromosome 5, 1264661: 1264661
3 NOP10 NM_018648.3(NOP10): c.100C> T (p.Arg34Trp) single nucleotide variant Pathogenic rs121908092 GRCh37 Chromosome 15, 34634264: 34634264
4 NHP2 NM_017838.3(NHP2): c.415T> C (p.Tyr139His) single nucleotide variant Pathogenic rs121908089 GRCh37 Chromosome 5, 177576761: 177576761
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.460T> A (p.Ter154Arg) single nucleotide variant Pathogenic rs121908091 GRCh37 Chromosome 5, 177576716: 177576716

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 10.65 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 intracellular ribonucleoprotein complex GO:0030529 9.54 NHP2 NOP10 TERT
3 nuclear chromosome, telomeric region GO:0000784 9.46 NHP2 TERT
4 Cajal body GO:0015030 9.4 NHP2 NOP10
5 small nucleolar ribonucleoprotein complex GO:0005732 9.32 NHP2 NOP10
6 box H/ACA snoRNP complex GO:0031429 9.26 NHP2 NOP10
7 box H/ACA scaRNP complex GO:0072589 9.16 NHP2 NOP10
8 box H/ACA telomerase RNP complex GO:0090661 8.96 NHP2 NOP10
9 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
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....