DKCB5
MCID: DYS152
MIFTS: 34

Dyskeratosis Congenita, Autosomal Recessive 5 (DKCB5)

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 Recessive 5

MalaCards integrated aliases for Dyskeratosis Congenita, Autosomal Recessive 5:

Name: Dyskeratosis Congenita, Autosomal Recessive 5 57
Dyskeratosis Congenita, Autosomal Recessive, 5 75 29 13 6 73
Dyskeratosis Congenita, Autosomal Dominant, 4 75 29 6 73
Dkcb5 57 12 75
Dkca4 12 75
Dyskeratosis Congenita, Autosomal Recessive, Type 5 ) 40
Dyskeratosis Congenita, Autosomal Dominant 4 57
Autosomal Recessive Dyskeratosis Congenita 5 12
Autosomal Dominant Dyskeratosis Congenita 4 12

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
variable severity
onset in early childhood
some patients may be asymptomatic and have only short telomeres
affected individuals may have biallelic or heterozygous mutations


HPO:

32
dyskeratosis congenita, autosomal recessive 5:
Onset and clinical course variable expressivity
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Dyskeratosis Congenita, Autosomal Recessive 5

UniProtKB/Swiss-Prot : 75 Dyskeratosis congenita, autosomal dominant, 4: 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, 5: 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. DKCB5 is characterized by onset of bone marrow failure and immunodeficiency in early childhood. Most patients also have growth and developmental delay and cerebellar hypoplasia, consistent with a clinical diagnosis of Hoyeraal-Hreidarsson syndrome.

MalaCards based summary : Dyskeratosis Congenita, Autosomal Recessive 5, also known as dyskeratosis congenita, autosomal recessive, 5, is related to dyskeratosis congenita autosomal dominant and dyskeratosis congenita. An important gene associated with Dyskeratosis Congenita, Autosomal Recessive 5 is RTEL1 (Regulator Of Telomere Elongation Helicase 1). Affiliated tissues include bone, skin and bone marrow, and related phenotypes are global developmental delay and microcephaly

Disease Ontology : 12 A dyskeratosis congenita that has material basis in an autosomal recessive mutation of RTEL1 on chromosome 20q13.33.

OMIM : 57 Dyskeratosis congenita (DKC) is a bone marrow failure syndrome characterized by severely shortened telomeres and diverse clinical symptoms. The classic presentation of DKC includes nail dystrophy, abnormal skin pigmentation, and oral leukoplakia. Hoyeraal-Hreidarsson syndrome (HHS) is a severe clinical variant of DKC that is characterized by intrauterine growth failure, microcephaly, developmental delay, immunodeficiency, bone marrow failure, and cerebellar hypoplasia. Patients with mutations in the RTEL1 gene tend to present with HHS (summary by Walne et al., 2013). For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (127550). (615190)

Related Diseases for Dyskeratosis Congenita, Autosomal Recessive 5

Symptoms & Phenotypes for Dyskeratosis Congenita, Autosomal Recessive 5

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Head:
microcephaly

Immunology:
leukopenia
hypogammaglobulinemia
immunodeficiency, primarily affecting b cell line

Skin Nails Hair Nails:
nail dystrophy (in some patients)

Skin Nails Hair Skin:
abnormal skin pigmentation (in some patients)
leukoplakia (in some patients)

Laboratory Abnormalities:
shortened telomeres in leukocytes
fibroblasts may have normal telomere lengths

Growth Other:
intrauterine growth retardation
postnatal growth retardation

Hematology:
bone marrow failure

Abdomen Gastrointestinal:
colitis (in some patients)
esophageal stenosis (in some patients)

Neurologic Central Nervous System:
developmental delay (in most patients)
cerebellar hypoplasia (in most patients)


Clinical features from OMIM:

615190

Human phenotypes related to Dyskeratosis Congenita, Autosomal Recessive 5:

32 (show all 12)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 32 hallmark (90%) HP:0001263
2 microcephaly 32 HP:0000252
3 immunodeficiency 32 HP:0002721
4 bone marrow hypocellularity 32 HP:0005528
5 nail dystrophy 32 occasional (7.5%) HP:0008404
6 intrauterine growth retardation 32 HP:0001511
7 postnatal growth retardation 32 HP:0008897
8 decreased antibody level in blood 32 HP:0004313
9 cerebellar hypoplasia 32 hallmark (90%) HP:0001321
10 esophageal stenosis 32 occasional (7.5%) HP:0010450
11 leukopenia 32 HP:0001882
12 colitis 32 occasional (7.5%) HP:0002583

Drugs & Therapeutics for Dyskeratosis Congenita, Autosomal Recessive 5

Search Clinical Trials , NIH Clinical Center for Dyskeratosis Congenita, Autosomal Recessive 5

Genetic Tests for Dyskeratosis Congenita, Autosomal Recessive 5

Genetic tests related to Dyskeratosis Congenita, Autosomal Recessive 5:

# Genetic test Affiliating Genes
1 Dyskeratosis Congenita, Autosomal Recessive, 5 29 RTEL1
2 Dyskeratosis Congenita, Autosomal Dominant, 4 29

Anatomical Context for Dyskeratosis Congenita, Autosomal Recessive 5

MalaCards organs/tissues related to Dyskeratosis Congenita, Autosomal Recessive 5:

41
Bone, Skin, Bone Marrow, Liver, Eye, B Cells

Publications for Dyskeratosis Congenita, Autosomal Recessive 5

Variations for Dyskeratosis Congenita, Autosomal Recessive 5

UniProtKB/Swiss-Prot genetic disease variations for Dyskeratosis Congenita, Autosomal Recessive 5:

75 (show all 11)
# Symbol AA change Variation ID SNP ID
1 RTEL1 p.Glu251Lys VAR_069714 rs398123019
2 RTEL1 p.Met492Ile VAR_069715 rs370343781
3 RTEL1 p.Glu591Asp VAR_069716 rs398123051
4 RTEL1 p.Ala621Thr VAR_069717 rs398123052
5 RTEL1 p.Ile699Met VAR_069719 rs398123048
6 RTEL1 p.Leu710Arg VAR_069720
7 RTEL1 p.Gly739Val VAR_069721 rs398123016
8 RTEL1 p.Val745Met VAR_069722 rs398123049
9 RTEL1 p.Lys897Glu VAR_069725
10 RTEL1 p.Arg957Trp VAR_069727 rs398123018
11 RTEL1 p.Phe964Leu VAR_069728 rs147014513

ClinVar genetic disease variations for Dyskeratosis Congenita, Autosomal Recessive 5:

6 (show top 50) (show all 430)
# Gene Variation Type Significance SNP ID Assembly Location
1 RTEL1 NM_032957.4(RTEL1): c.2288G> T (p.Gly763Val) single nucleotide variant Uncertain significance rs398123016 GRCh37 Chromosome 20, 62321514: 62321514
2 RTEL1 NM_032957.4(RTEL1): c.2288G> T (p.Gly763Val) single nucleotide variant Uncertain significance rs398123016 GRCh38 Chromosome 20, 63690161: 63690161
3 RTEL1 RTEL1: c.2402G> A (p.Arg801His) single nucleotide variant Pathogenic/Likely pathogenic rs201540674 GRCh37 Chromosome 20, 62326972: 62326972
4 RTEL1 RTEL1: c.2402G> A (p.Arg801His) single nucleotide variant Pathogenic/Likely pathogenic rs201540674 GRCh38 Chromosome 20, 63695619: 63695619
5 RTEL1 NM_032957.4(RTEL1): c.1548G> T (p.Met516Ile) single nucleotide variant Likely pathogenic rs370343781 GRCh37 Chromosome 20, 62319118: 62319118
6 RTEL1 NM_032957.4(RTEL1): c.1548G> T (p.Met516Ile) single nucleotide variant Likely pathogenic rs370343781 GRCh38 Chromosome 20, 63687765: 63687765
7 RTEL1 NM_016434.3(RTEL1): c.2920C> T (p.Arg974Ter) single nucleotide variant Pathogenic rs398123017 GRCh37 Chromosome 20, 62324564: 62324564
8 RTEL1 NM_016434.3(RTEL1): c.2920C> T (p.Arg974Ter) single nucleotide variant Pathogenic rs398123017 GRCh38 Chromosome 20, 63693211: 63693211
9 RTEL1 NM_032957.4(RTEL1): c.2941C> T (p.Arg981Trp) single nucleotide variant Likely pathogenic rs398123018 GRCh37 Chromosome 20, 62324513: 62324513
10 RTEL1 NM_032957.4(RTEL1): c.2941C> T (p.Arg981Trp) single nucleotide variant Likely pathogenic rs398123018 GRCh38 Chromosome 20, 63693160: 63693160
11 RTEL1 NM_032957.4(RTEL1): c.823G> A (p.Glu275Lys) single nucleotide variant Uncertain significance rs398123019 GRCh37 Chromosome 20, 62303960: 62303960
12 RTEL1 NM_032957.4(RTEL1): c.823G> A (p.Glu275Lys) single nucleotide variant Uncertain significance rs398123019 GRCh38 Chromosome 20, 63672607: 63672607
13 RTEL1 NM_032957.4(RTEL1): c.3724+78T> C single nucleotide variant Uncertain significance rs587777037 GRCh37 Chromosome 20, 62326911: 62326911
14 RTEL1 NM_032957.4(RTEL1): c.3724+78T> C single nucleotide variant Uncertain significance rs587777037 GRCh38 Chromosome 20, 63695558: 63695558
15 RTEL1 NM_016434.3(RTEL1): c.2097C> G (p.Ile699Met) single nucleotide variant Pathogenic rs398123048 GRCh37 Chromosome 20, 62321174: 62321174
16 RTEL1 NM_016434.3(RTEL1): c.2097C> G (p.Ile699Met) single nucleotide variant Pathogenic rs398123048 GRCh38 Chromosome 20, 63689821: 63689821
17 RTEL1 NM_016434.3(RTEL1): c.2233G> A (p.Val745Met) single nucleotide variant Pathogenic rs398123049 GRCh37 Chromosome 20, 62321531: 62321531
18 RTEL1 NM_016434.3(RTEL1): c.2233G> A (p.Val745Met) single nucleotide variant Pathogenic rs398123049 GRCh38 Chromosome 20, 63690178: 63690178
19 RTEL1 NM_032957.4(RTEL1): c.2213+5G> A single nucleotide variant Uncertain significance rs398123050 GRCh37 Chromosome 20, 62321223: 62321223
20 RTEL1 NM_032957.4(RTEL1): c.2213+5G> A single nucleotide variant Uncertain significance rs398123050 GRCh38 Chromosome 20, 63689870: 63689870
21 RTEL1 NM_032957.4(RTEL1): c.1845G> T (p.Glu615Asp) single nucleotide variant Pathogenic rs398123051 GRCh37 Chromosome 20, 62319931: 62319931
22 RTEL1 NM_032957.4(RTEL1): c.1845G> T (p.Glu615Asp) single nucleotide variant Pathogenic rs398123051 GRCh38 Chromosome 20, 63688578: 63688578
23 RTEL1 NM_032957.4(RTEL1): c.3028C> T (p.Arg1010Ter) single nucleotide variant Pathogenic/Likely pathogenic rs373740199 GRCh37 Chromosome 20, 62324600: 62324600
24 RTEL1 NM_032957.4(RTEL1): c.3028C> T (p.Arg1010Ter) single nucleotide variant Pathogenic/Likely pathogenic rs373740199 GRCh38 Chromosome 20, 63693247: 63693247
25 RTEL1 NM_032957.4(RTEL1): c.1933G> A (p.Ala645Thr) single nucleotide variant Pathogenic rs398123052 GRCh37 Chromosome 20, 62320468: 62320468
26 RTEL1 NM_032957.4(RTEL1): c.1933G> A (p.Ala645Thr) single nucleotide variant Pathogenic rs398123052 GRCh38 Chromosome 20, 63689115: 63689115
27 RTEL1 NM_032957.4(RTEL1): c.1523C> T (p.Pro508Leu) single nucleotide variant Uncertain significance rs786205700 GRCh37 Chromosome 20, 62319093: 62319093
28 RTEL1 NM_032957.4(RTEL1): c.1523C> T (p.Pro508Leu) single nucleotide variant Uncertain significance rs786205700 GRCh38 Chromosome 20, 63687740: 63687740
29 RTEL1 NM_032957.4(RTEL1): c.2618G> A (p.Gly873Asp) single nucleotide variant Benign/Likely benign rs190887884 GRCh38 Chromosome 20, 63690937: 63690937
30 RTEL1 NM_032957.4(RTEL1): c.2618G> A (p.Gly873Asp) single nucleotide variant Benign/Likely benign rs190887884 GRCh37 Chromosome 20, 62322290: 62322290
31 RTEL1 NM_032957.4(RTEL1): c.3687C> T (p.Ser1229=) single nucleotide variant Conflicting interpretations of pathogenicity rs797045923 GRCh38 Chromosome 20, 63695443: 63695443
32 RTEL1 NM_032957.4(RTEL1): c.3687C> T (p.Ser1229=) single nucleotide variant Conflicting interpretations of pathogenicity rs797045923 GRCh37 Chromosome 20, 62326796: 62326796
33 RTEL1 NM_016434.3(RTEL1): c.2957G> A (p.Arg986Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs146221660 GRCh38 Chromosome 20, 63693248: 63693248
34 RTEL1 NM_016434.3(RTEL1): c.2957G> A (p.Arg986Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs146221660 GRCh37 Chromosome 20, 62324601: 62324601
35 RTEL1 NM_032957.4(RTEL1): c.1720C> T (p.Arg574Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs369419645 GRCh37 Chromosome 20, 62319665: 62319665
36 RTEL1 NM_032957.4(RTEL1): c.1720C> T (p.Arg574Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs369419645 GRCh38 Chromosome 20, 63688312: 63688312
37 RTEL1 NM_032957.4(RTEL1): c.245C> T (p.Pro82Leu) single nucleotide variant Uncertain significance rs143461704 GRCh37 Chromosome 20, 62292793: 62292793
38 RTEL1 NM_032957.4(RTEL1): c.245C> T (p.Pro82Leu) single nucleotide variant Uncertain significance rs143461704 GRCh38 Chromosome 20, 63661440: 63661440
39 RTEL1 NM_032957.4(RTEL1): c.431C> T (p.Thr144Ile) single nucleotide variant Likely benign rs41297642 GRCh38 Chromosome 20, 63662509: 63662509
40 RTEL1 NM_032957.4(RTEL1): c.431C> T (p.Thr144Ile) single nucleotide variant Likely benign rs41297642 GRCh37 Chromosome 20, 62293862: 62293862
41 RTEL1 NM_001283009.1(RTEL1): c.973C> T (p.Leu325=) single nucleotide variant Conflicting interpretations of pathogenicity rs142739953 GRCh38 Chromosome 20, 63678282: 63678282
42 RTEL1 NM_001283009.1(RTEL1): c.973C> T (p.Leu325=) single nucleotide variant Conflicting interpretations of pathogenicity rs142739953 GRCh37 Chromosome 20, 62309635: 62309635
43 RTEL1 NM_032957.4(RTEL1): c.1332C> T (p.Ser444=) single nucleotide variant Benign/Likely benign rs188479221 GRCh37 Chromosome 20, 62316944: 62316944
44 RTEL1 NM_032957.4(RTEL1): c.1332C> T (p.Ser444=) single nucleotide variant Benign/Likely benign rs188479221 GRCh38 Chromosome 20, 63685591: 63685591
45 RTEL1 NM_001283009.1(RTEL1): c.1349-9G> A single nucleotide variant Conflicting interpretations of pathogenicity rs772899702 GRCh38 Chromosome 20, 63687629: 63687629
46 RTEL1 NM_001283009.1(RTEL1): c.1349-9G> A single nucleotide variant Conflicting interpretations of pathogenicity rs772899702 GRCh37 Chromosome 20, 62318982: 62318982
47 RTEL1 NM_001283009.1(RTEL1): c.1727G> A (p.Arg576His) single nucleotide variant Benign rs115423936 GRCh38 Chromosome 20, 63688532: 63688532
48 RTEL1 NM_001283009.1(RTEL1): c.1727G> A (p.Arg576His) single nucleotide variant Benign rs115423936 GRCh37 Chromosome 20, 62319885: 62319885
49 RTEL1 NM_032957.4(RTEL1): c.1833G> A (p.Pro611=) single nucleotide variant Benign rs116900568 GRCh38 Chromosome 20, 63688566: 63688566
50 RTEL1 NM_032957.4(RTEL1): c.1833G> A (p.Pro611=) single nucleotide variant Benign rs116900568 GRCh37 Chromosome 20, 62319919: 62319919

Expression for Dyskeratosis Congenita, Autosomal Recessive 5

Search GEO for disease gene expression data for Dyskeratosis Congenita, Autosomal Recessive 5.

Pathways for Dyskeratosis Congenita, Autosomal Recessive 5

GO Terms for Dyskeratosis Congenita, Autosomal Recessive 5

Biological processes related to Dyskeratosis Congenita, Autosomal Recessive 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to DNA damage stimulus GO:0006974 9.43 RTEL1 RTEL1-TNFRSF6B
2 DNA repair GO:0006281 9.4 RTEL1 RTEL1-TNFRSF6B
3 DNA replication GO:0006260 9.37 RTEL1 RTEL1-TNFRSF6B
4 DNA recombination GO:0006310 9.32 RTEL1 RTEL1-TNFRSF6B
5 DNA duplex unwinding GO:0032508 9.26 RTEL1 RTEL1-TNFRSF6B
6 nucleobase-containing compound metabolic process GO:0006139 9.16 RTEL1 RTEL1-TNFRSF6B
7 telomere maintenance GO:0000723 8.96 RTEL1 RTEL1-TNFRSF6B
8 regulation of double-strand break repair via homologous recombination GO:0010569 8.62 RTEL1 RTEL1-TNFRSF6B

Molecular functions related to Dyskeratosis Congenita, Autosomal Recessive 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 helicase activity GO:0004386 9.37 RTEL1 RTEL1-TNFRSF6B
2 iron-sulfur cluster binding GO:0051536 9.32 RTEL1 RTEL1-TNFRSF6B
3 4 iron, 4 sulfur cluster binding GO:0051539 9.26 RTEL1 RTEL1-TNFRSF6B
4 ATP-dependent DNA helicase activity GO:0004003 9.16 RTEL1 RTEL1-TNFRSF6B
5 ATP-dependent helicase activity GO:0008026 8.96 RTEL1 RTEL1-TNFRSF6B
6 hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides GO:0016818 8.62 RTEL1 RTEL1-TNFRSF6B

Sources for Dyskeratosis Congenita, Autosomal Recessive 5

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
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
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
Content
Loading form....