MCID: DYS152
MIFTS: 34

Dyskeratosis Congenita, Autosomal Recessive 5

Categories: Genetic diseases, Skin diseases, Blood diseases, Rare diseases, Neuronal diseases, Eye diseases, Fetal diseases, Immune 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 pulmonary fibrosis and/or bone marrow failure, telomere-related, 3. An important gene associated with Dyskeratosis Congenita, Autosomal Recessive 5 is RTEL1 (Regulator Of Telomere Elongation Helicase 1). Affiliated tissues include bone marrow, bone and skin, and related phenotypes are microcephaly and global developmental delay

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

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 Dominant, 4 29
2 Dyskeratosis Congenita, Autosomal Recessive, 5 29 RTEL1

Anatomical Context for Dyskeratosis Congenita, Autosomal Recessive 5

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

41
Bone Marrow, Bone, Skin, Liver, 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

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

6
(show top 50) (show all 202)
# Gene Variation Type Significance SNP ID Assembly Location
1 RTEL1 RTEL1: c.2402G> A (p.Arg801His) single nucleotide variant Pathogenic/Likely pathogenic rs201540674 GRCh37 Chromosome 20, 62326972: 62326972
2 RTEL1 RTEL1: c.2402G> A (p.Arg801His) single nucleotide variant Pathogenic/Likely pathogenic rs201540674 GRCh38 Chromosome 20, 63695619: 63695619
3 RTEL1 NM_032957.4(RTEL1): c.1548G> T (p.Met516Ile) single nucleotide variant Likely pathogenic rs370343781 GRCh37 Chromosome 20, 62319118: 62319118
4 RTEL1 NM_032957.4(RTEL1): c.1548G> T (p.Met516Ile) single nucleotide variant Likely pathogenic rs370343781 GRCh38 Chromosome 20, 63687765: 63687765
5 RTEL1 NM_016434.3(RTEL1): c.2920C> T (p.Arg974Ter) single nucleotide variant Pathogenic rs398123017 GRCh37 Chromosome 20, 62324564: 62324564
6 RTEL1 NM_016434.3(RTEL1): c.2920C> T (p.Arg974Ter) single nucleotide variant Pathogenic rs398123017 GRCh38 Chromosome 20, 63693211: 63693211
7 RTEL1 NM_032957.4(RTEL1): c.2941C> T (p.Arg981Trp) single nucleotide variant Likely pathogenic rs398123018 GRCh37 Chromosome 20, 62324513: 62324513
8 RTEL1 NM_032957.4(RTEL1): c.2941C> T (p.Arg981Trp) single nucleotide variant Likely pathogenic rs398123018 GRCh38 Chromosome 20, 63693160: 63693160
9 RTEL1 NM_032957.4(RTEL1): c.823G> A (p.Glu275Lys) single nucleotide variant Pathogenic rs398123019 GRCh37 Chromosome 20, 62303960: 62303960
10 RTEL1 NM_032957.4(RTEL1): c.823G> A (p.Glu275Lys) single nucleotide variant Pathogenic rs398123019 GRCh38 Chromosome 20, 63672607: 63672607
11 RTEL1 NM_001283009.1(RTEL1): c.3730T> C (p.Cys1244Arg) single nucleotide variant Pathogenic rs587777037 GRCh37 Chromosome 20, 62326911: 62326911
12 RTEL1 NM_001283009.1(RTEL1): c.3730T> C (p.Cys1244Arg) single nucleotide variant Pathogenic rs587777037 GRCh38 Chromosome 20, 63695558: 63695558
13 RTEL1 NM_016434.3(RTEL1): c.2097C> G (p.Ile699Met) single nucleotide variant Pathogenic rs398123048 GRCh37 Chromosome 20, 62321174: 62321174
14 RTEL1 NM_016434.3(RTEL1): c.2097C> G (p.Ile699Met) single nucleotide variant Pathogenic rs398123048 GRCh38 Chromosome 20, 63689821: 63689821
15 RTEL1 NM_016434.3(RTEL1): c.2233G> A (p.Val745Met) single nucleotide variant Pathogenic rs398123049 GRCh37 Chromosome 20, 62321531: 62321531
16 RTEL1 NM_016434.3(RTEL1): c.2233G> A (p.Val745Met) single nucleotide variant Pathogenic rs398123049 GRCh38 Chromosome 20, 63690178: 63690178
17 RTEL1 NM_016434.3(RTEL1): c.2141+5G> A single nucleotide variant Pathogenic rs398123050 GRCh37 Chromosome 20, 62321223: 62321223
18 RTEL1 NM_016434.3(RTEL1): c.2141+5G> A single nucleotide variant Pathogenic rs398123050 GRCh38 Chromosome 20, 63689870: 63689870
19 RTEL1 NM_032957.4(RTEL1): c.1845G> T (p.Glu615Asp) single nucleotide variant Pathogenic rs398123051 GRCh37 Chromosome 20, 62319931: 62319931
20 RTEL1 NM_032957.4(RTEL1): c.1845G> T (p.Glu615Asp) single nucleotide variant Pathogenic rs398123051 GRCh38 Chromosome 20, 63688578: 63688578
21 RTEL1 NM_032957.4(RTEL1): c.3028C> T (p.Arg1010Ter) single nucleotide variant Pathogenic/Likely pathogenic rs373740199 GRCh37 Chromosome 20, 62324600: 62324600
22 RTEL1 NM_032957.4(RTEL1): c.3028C> T (p.Arg1010Ter) single nucleotide variant Pathogenic/Likely pathogenic rs373740199 GRCh38 Chromosome 20, 63693247: 63693247
23 RTEL1 NM_032957.4(RTEL1): c.1933G> A (p.Ala645Thr) single nucleotide variant Pathogenic rs398123052 GRCh37 Chromosome 20, 62320468: 62320468
24 RTEL1 NM_032957.4(RTEL1): c.1933G> A (p.Ala645Thr) single nucleotide variant Pathogenic rs398123052 GRCh38 Chromosome 20, 63689115: 63689115
25 RTEL1 NM_032957.4(RTEL1): c.2618G> A (p.Gly873Asp) single nucleotide variant Benign/Likely benign rs190887884 GRCh38 Chromosome 20, 63690937: 63690937
26 RTEL1 NM_032957.4(RTEL1): c.2618G> A (p.Gly873Asp) single nucleotide variant Benign/Likely benign rs190887884 GRCh37 Chromosome 20, 62322290: 62322290
27 RTEL1 NM_032957.4(RTEL1): c.1346T> C (p.Ile449Thr) single nucleotide variant no interpretation for the single variant rs863224915 GRCh37 Chromosome 20, 62317151: 62317151
28 RTEL1 NM_032957.4(RTEL1): c.1346T> C (p.Ile449Thr) single nucleotide variant no interpretation for the single variant rs863224915 GRCh38 Chromosome 20, 63685798: 63685798
29 RTEL1 NM_032957.4(RTEL1): c.245C> T (p.Pro82Leu) single nucleotide variant Uncertain significance rs143461704 GRCh37 Chromosome 20, 62292793: 62292793
30 RTEL1 NM_032957.4(RTEL1): c.245C> T (p.Pro82Leu) single nucleotide variant Uncertain significance rs143461704 GRCh38 Chromosome 20, 63661440: 63661440
31 RTEL1 NM_032957.4(RTEL1): c.431C> T (p.Thr144Ile) single nucleotide variant Likely benign rs41297642 GRCh37 Chromosome 20, 62293862: 62293862
32 RTEL1 NM_032957.4(RTEL1): c.431C> T (p.Thr144Ile) single nucleotide variant Likely benign rs41297642 GRCh38 Chromosome 20, 63662509: 63662509
33 RTEL1 NM_001283009.1(RTEL1): c.973C> T (p.Leu325=) single nucleotide variant Conflicting interpretations of pathogenicity rs142739953 GRCh37 Chromosome 20, 62309635: 62309635
34 RTEL1 NM_001283009.1(RTEL1): c.973C> T (p.Leu325=) single nucleotide variant Conflicting interpretations of pathogenicity rs142739953 GRCh38 Chromosome 20, 63678282: 63678282
35 RTEL1 NM_032957.4(RTEL1): c.1332C> T (p.Ser444=) single nucleotide variant Benign/Likely benign rs188479221 GRCh38 Chromosome 20, 63685591: 63685591
36 RTEL1 NM_032957.4(RTEL1): c.1332C> T (p.Ser444=) single nucleotide variant Benign/Likely benign rs188479221 GRCh37 Chromosome 20, 62316944: 62316944
37 RTEL1 NM_001283009.1(RTEL1): c.1349-9G> A single nucleotide variant Conflicting interpretations of pathogenicity rs772899702 GRCh38 Chromosome 20, 63687629: 63687629
38 RTEL1 NM_001283009.1(RTEL1): c.1349-9G> A single nucleotide variant Conflicting interpretations of pathogenicity rs772899702 GRCh37 Chromosome 20, 62318982: 62318982
39 RTEL1 NM_001283009.1(RTEL1): c.1727G> A (p.Arg576His) single nucleotide variant Benign rs115423936 GRCh37 Chromosome 20, 62319885: 62319885
40 RTEL1 NM_001283009.1(RTEL1): c.1727G> A (p.Arg576His) single nucleotide variant Benign rs115423936 GRCh38 Chromosome 20, 63688532: 63688532
41 RTEL1 NM_032957.4(RTEL1): c.1833G> A (p.Pro611=) single nucleotide variant Benign rs116900568 GRCh37 Chromosome 20, 62319919: 62319919
42 RTEL1 NM_032957.4(RTEL1): c.1833G> A (p.Pro611=) single nucleotide variant Benign rs116900568 GRCh38 Chromosome 20, 63688566: 63688566
43 RTEL1 NM_032957.4(RTEL1): c.2385_2387delAGA (p.Glu795del) deletion Benign/Likely benign rs558133631 GRCh38 Chromosome 20, 63690341: 63690343
44 RTEL1 NM_032957.4(RTEL1): c.2385_2387delAGA (p.Glu795del) deletion Benign/Likely benign rs558133631 GRCh37 Chromosome 20, 62321694: 62321696
45 RTEL1 NM_032957.4(RTEL1): c.2672C> T (p.Pro891Leu) single nucleotide variant Uncertain significance rs139083375 GRCh38 Chromosome 20, 63691785: 63691785
46 RTEL1 NM_032957.4(RTEL1): c.2672C> T (p.Pro891Leu) single nucleotide variant Uncertain significance rs139083375 GRCh37 Chromosome 20, 62323138: 62323138
47 RTEL1 NM_032957.4(RTEL1): c.2847C> T (p.Ser949=) single nucleotide variant Benign/Likely benign rs12480346 GRCh38 Chromosome 20, 63692927: 63692927
48 RTEL1 NM_032957.4(RTEL1): c.2847C> T (p.Ser949=) single nucleotide variant Benign/Likely benign rs12480346 GRCh37 Chromosome 20, 62324280: 62324280
49 RTEL1 NM_032957.4(RTEL1): c.2970G> C (p.Glu990Asp) single nucleotide variant Benign/Likely benign rs115464632 GRCh37 Chromosome 20, 62324542: 62324542
50 RTEL1 NM_032957.4(RTEL1): c.2970G> C (p.Glu990Asp) single nucleotide variant Benign/Likely benign rs115464632 GRCh38 Chromosome 20, 63693189: 63693189

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 nucleobase-containing compound metabolic process GO:0006139 9.26 RTEL1 RTEL1-TNFRSF6B
6 DNA duplex unwinding GO:0032508 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 hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides GO:0016818 8.96 RTEL1 RTEL1-TNFRSF6B
6 ATP-dependent helicase activity GO:0008026 8.62 RTEL1 RTEL1-TNFRSF6B

Sources for Dyskeratosis Congenita, Autosomal Recessive 5

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