DKCB5
MCID: DYS152
MIFTS: 40

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 56
Dyskeratosis Congenita, Autosomal Recessive, 5 73 29 13 6 71
Dyskeratosis Congenita, Autosomal Dominant, 4 73 29 6 71
Dkcb5 56 12 73
Autosomal Recessive Dyskeratosis Congenita 5 12 15
Autosomal Dominant Dyskeratosis Congenita 4 12 15
Dkca4 12 73
Dyskeratosis Congenita, Autosomal Recessive, Type 5 39
Dyskeratosis Congenita, Autosomal Dominant 4 56

Characteristics:

OMIM:

56
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:

31
dyskeratosis congenita, autosomal recessive 5:
Inheritance autosomal dominant inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity


Classifications:



External Ids:

Disease Ontology 12 DOID:0070020 DOID:0070022
OMIM 56 615190
OMIM Phenotypic Series 56 PS127550
MeSH 43 D019871
UMLS 71 C3554656 C3808802

Summaries for Dyskeratosis Congenita, Autosomal Recessive 5

UniProtKB/Swiss-Prot : 73 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 and fanconi anemia, complementation group j. An important gene associated with Dyskeratosis Congenita, Autosomal Recessive 5 is RTEL1 (Regulator Of Telomere Elongation Helicase 1). Affiliated tissues include bone, bone marrow and skin, and related phenotypes are global developmental delay and cerebellar hypoplasia

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

OMIM : 56 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

Human phenotypes related to Dyskeratosis Congenita, Autosomal Recessive 5:

31 (show all 12)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 hallmark (90%) HP:0001263
2 cerebellar hypoplasia 31 hallmark (90%) HP:0001321
3 nail dystrophy 31 occasional (7.5%) HP:0008404
4 esophageal stenosis 31 occasional (7.5%) HP:0010450
5 colitis 31 occasional (7.5%) HP:0002583
6 intrauterine growth retardation 31 HP:0001511
7 microcephaly 31 HP:0000252
8 immunodeficiency 31 HP:0002721
9 bone marrow hypocellularity 31 HP:0005528
10 postnatal growth retardation 31 HP:0008897
11 decreased antibody level in blood 31 HP:0004313
12 leukopenia 31 HP:0001882

Symptoms via clinical synopsis from OMIM:

56
Growth Other:
intrauterine growth retardation
postnatal growth retardation

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

Head And Neck Head:
microcephaly

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

MGI Mouse Phenotypes related to Dyskeratosis Congenita, Autosomal Recessive 5:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.02 AVEN DHX36 PIF1 RTEL1 SUPV3L1

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:

40
Bone, Bone Marrow, Skin, Liver, B Cells, Eye

Publications for Dyskeratosis Congenita, Autosomal Recessive 5

Articles related to Dyskeratosis Congenita, Autosomal Recessive 5:

# Title Authors PMID Year
1
Inherited mutations in the helicase RTEL1 cause telomere dysfunction and Hoyeraal-Hreidarsson syndrome. 56 6
23959892 2013
2
Human RTEL1 deficiency causes Hoyeraal-Hreidarsson syndrome with short telomeres and genome instability. 56 6
23591994 2013
3
Germline mutations of regulator of telomere elongation helicase 1, RTEL1, in Dyskeratosis congenita. 56 6
23329068 2013
4
Constitutional mutations in RTEL1 cause severe dyskeratosis congenita. 56 6
23453664 2013
5
Diminished telomeric 3' overhangs are associated with telomere dysfunction in Hoyeraal-Hreidarsson syndrome. 56 6
19461895 2009
6
Rare variants in RTEL1 are associated with familial interstitial pneumonia. 6
25607374 2015
7
Dyskeratosis Congenita 6
20301779 2009

Variations for Dyskeratosis Congenita, Autosomal Recessive 5

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

6 (show top 50) (show all 229) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RTEL1 NM_016434.3(RTEL1):c.2920C>T (p.Arg974Ter)SNV Pathogenic 42020 rs398123017 20:62324564-62324564 20:63693211-63693211
2 RTEL1 NM_016434.3(RTEL1):c.2097C>G (p.Ile699Met)SNV Pathogenic 65413 rs398123048 20:62321174-62321174 20:63689821-63689821
3 RTEL1 NM_016434.3(RTEL1):c.2233G>A (p.Val745Met)SNV Pathogenic 65414 rs398123049 20:62321531-62321531 20:63690178-63690178
4 RTEL1 NM_016434.3(RTEL1):c.1773G>T (p.Glu591Asp)SNV Pathogenic 65416 rs398123051 20:62319931-62319931 20:63688578-63688578
5 RTEL1 NM_016434.3(RTEL1):c.1861G>A (p.Ala621Thr)SNV Pathogenic 65418 rs398123052 20:62320468-62320468 20:63689115-63689115
6 RTEL1 NM_032957.4(RTEL1):c.607G>T (p.Glu203Ter)SNV Pathogenic 540926 rs1555899932 20:62294239-62294239 20:63662886-63662886
7 RTEL1 NM_016434.3(RTEL1):c.1001_1014del (p.Leu334fs)deletion Pathogenic 665122 20:62309662-62309675 20:63678309-63678322
8 RTEL1 NM_032957.4(RTEL1):c.3028C>T (p.Arg1010Ter)SNV Pathogenic/Likely pathogenic 65417 rs373740199 20:62324600-62324600 20:63693247-63693247
9 RTEL1 NM_001283009.1(RTEL1):c.3791G>A (p.Arg1264His)SNV Pathogenic/Likely pathogenic 42018 rs201540674 20:62326972-62326972 20:63695619-63695619
10 RTEL1 NM_032957.4(RTEL1):c.1548G>T (p.Met516Ile)SNV Pathogenic/Likely pathogenic 42019 rs370343781 20:62319118-62319118 20:63687765-63687765
11 RTEL1 NM_016434.3(RTEL1):c.2812del (p.Leu938fs)deletion Pathogenic/Likely pathogenic 577500 rs1449687529 20:62324313-62324313 20:63692960-63692960
12 RTEL1 NM_032957.4(RTEL1):c.2725-2A>CSNV Likely pathogenic 558451 rs1555812834 20:62324156-62324156 20:63692803-63692803
13 RTEL1 NM_016434.3(RTEL1):c.3104dup (p.Thr1036fs)duplication Likely pathogenic 553318 rs1555814044 20:62325831-62325832 20:63694478-63694479
14 RTEL1 NM_032957.4(RTEL1):c.3182-2A>CSNV Likely pathogenic 550440 rs377461417 20:62326092-62326092 20:63694739-63694739
15 RTEL1 NM_032957.4(RTEL1):c.3182-2A>TSNV Likely pathogenic 551868 rs377461417 20:62326092-62326092 20:63694739-63694739
16 RTEL1 NM_016434.3(RTEL1):c.1963dup (p.Arg655fs)duplication Likely pathogenic 550933 rs1555811742 20:62320934-62320935 20:63689581-63689582
17 RTEL1 NM_032957.4(RTEL1):c.1668-1G>ASNV Likely pathogenic 552420 rs1555811386 20:62319491-62319491 20:63688138-63688138
18 RTEL1 NM_032957.4(RTEL1):c.597C>A (p.Tyr199Ter)SNV Likely pathogenic 555440 rs1161373315 20:62294229-62294229 20:63662876-63662876
19 RTEL1 NM_016434.3(RTEL1):c.897del (p.Phe299fs)deletion Likely pathogenic 558110 rs1555901832 20:62305424-62305424 20:63674071-63674071
20 RTEL1 NM_032957.4(RTEL1):c.2953A>T (p.Lys985Ter)SNV Likely pathogenic 551394 rs1555813144 20:62324525-62324525 20:63693172-63693172
21 RTEL1 NM_032957.4(RTEL1):c.3202C>T (p.Gln1068Ter)SNV Likely pathogenic 552188 rs1415449695 20:62326114-62326114 20:63694761-63694761
22 RTEL1 NM_016434.3(RTEL1):c.3334del (p.Leu1112fs)deletion Likely pathogenic 557947 rs1555814334 20:62326314-62326314 20:63694961-63694961
23 RTEL1 NM_032957.4(RTEL1):c.3416-2A>GSNV Likely pathogenic 554371 rs980695424 20:62326417-62326417 20:63695064-63695064
24 RTEL1 NM_032957.4(RTEL1):c.3448C>T (p.Gln1150Ter)SNV Likely pathogenic 556483 rs778734749 20:62326451-62326451 20:63695098-63695098
25 RTEL1 NM_032957.4(RTEL1):c.2941C>T (p.Arg981Trp)SNV Likely pathogenic 42021 rs398123018 20:62324513-62324513 20:63693160-63693160
26 RTEL1 NM_032957.4(RTEL1):c.442C>T (p.Arg148Ter)SNV Likely pathogenic 449904 rs80224512 20:62293873-62293873 20:63662520-63662520
27 RTEL1 NM_001283010.1(RTEL1):c.-212_-211deldeletion Likely pathogenic 554560 rs773025155 20:62293961-62293962 20:63662608-63662609
28 RTEL1 NM_032957.4(RTEL1):c.1109+1G>TSNV Likely pathogenic 553724 rs895722334 20:62309700-62309700 20:63678347-63678347
29 RTEL1 NM_016434.3(RTEL1):c.2533del (p.Ala845fs)deletion Likely pathogenic 555488 rs1555812228 20:62322275-62322275 20:63690922-63690922
30 RTEL1 NM_016434.3(RTEL1):c.2635del (p.Arg879fs)deletion Likely pathogenic 555380 rs1555812480 20:62323172-62323172 20:63691819-63691819
31 RTEL1 NM_032957.4(RTEL1):c.2923+1G>TSNV Likely pathogenic 558015 rs1421904176 20:62324357-62324357 20:63693004-63693004
32 RTEL1 NM_016434.3(RTEL1):c.2858del (p.Tyr953fs)deletion Likely pathogenic 556425 rs1555813123 20:62324502-62324502 20:63693149-63693149
33 RTEL1 NM_032957.4(RTEL1):c.2686C>T (p.Arg896Ter)SNV Likely pathogenic 554068 rs961593162 20:62323152-62323152 20:63691799-63691799
34 RTEL1 NM_032957.4(RTEL1):c.702C>A (p.Tyr234Ter)SNV Likely pathogenic 554988 rs1555901000 20:62298837-62298837 20:63667484-63667484
35 RTEL1 NM_032957.4(RTEL1):c.721C>T (p.Gln241Ter)SNV Likely pathogenic 558476 rs780546933 20:62298856-62298856 20:63667503-63667503
36 RTEL1 NM_016434.3(RTEL1):c.2021dup (p.Gln675fs)duplication Likely pathogenic 558467 rs1263776141 20:62320992-62320993 20:63689639-63689640
37 RTEL1 NM_032957.4(RTEL1):c.2332C>T (p.Arg778Ter)SNV Likely pathogenic 552546 rs377024903 20:62321558-62321558 20:63690205-63690205
38 RTEL1 NM_032957.4(RTEL1):c.2337+2T>ASNV Likely pathogenic 555575 rs1555811966 20:62321565-62321565 20:63690212-63690212
39 RTEL1 NM_032957.4(RTEL1):c.2486-2A>GSNV Likely pathogenic 556385 rs1555812178 20:62322156-62322156 20:63690803-63690803
40 RTEL1 NM_016434.3(RTEL1):c.2587_2590del (p.Ser863fs)deletion Likely pathogenic 555667 rs752833281 20:62323122-62323125 20:63691769-63691772
41 RTEL1 NM_016434.3(RTEL1):c.3652+63_3652+64delshort repeat Likely pathogenic 656263 20:62326893-62326894 20:63695540-63695541
42 RTEL1 NM_001283010.1(RTEL1):c.232_250+72deldeletion Likely pathogenic 651186 20:62305400-62305490 20:63674047-63674137
43 RTEL1 NM_016434.3(RTEL1):c.1596-1_1596delinsAAindel Likely pathogenic 639828 20:62319491-62319492 20:63688138-63688139
44 RTEL1 NM_032957.4(RTEL1):c.3059C>A (p.Pro1020His)SNV Conflicting interpretations of pathogenicity 436594 rs373210484 20:62324631-62324631 20:63693278-63693278
45 RTEL1 NM_032957.4(RTEL1):c.1720C>T (p.Arg574Cys)SNV Conflicting interpretations of pathogenicity 422356 rs369419645 20:62319665-62319665 20:63688312-63688312
46 RTEL1 NM_032957.4(RTEL1):c.3687C>T (p.Ser1229=)SNV Conflicting interpretations of pathogenicity 212075 rs797045923 20:62326796-62326796 20:63695443-63695443
47 RTEL1 NM_016434.3(RTEL1):c.2957G>A (p.Arg986Gln)SNV Conflicting interpretations of pathogenicity 217285 rs146221660 20:62324601-62324601 20:63693248-63693248
48 RTEL1 NM_032957.4(RTEL1):c.3724+13G>TSNV Conflicting interpretations of pathogenicity 557461 rs1177347580 20:62326846-62326846 20:63695493-63695493
49 RTEL1 NM_032957.4(RTEL1):c.3724+81C>GSNV Uncertain significance 558115 rs1555814729 20:62326914-62326914 20:63695561-63695561
50 RTEL1 NM_032957.4(RTEL1):c.*2A>GSNV Uncertain significance 558677 rs1555814876 20:62327140-62327140 20:63695787-63695787

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

73 (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

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

Cellular components related to Dyskeratosis Congenita, Autosomal Recessive 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromosome, telomeric region GO:0000781 8.62 RTEL1 DHX36

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

# Name GO ID Score Top Affiliating Genes
1 DNA replication GO:0006260 9.37 RTEL1 PIF1
2 DNA recombination GO:0006310 9.33 SUPV3L1 RTEL1 PIF1
3 telomere maintenance GO:0000723 9.32 RTEL1 PIF1
4 positive regulation of telomere maintenance GO:0032206 9.26 RTEL1 DHX36
5 DNA duplex unwinding GO:0032508 9.02 SUPV3L1 RTEL1 PIF1 HFM1 DHX36
6 positive regulation of telomere maintenance via telomere lengthening GO:1904358 8.96 RTEL1 DHX36

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

# Name GO ID Score Top Affiliating Genes
1 DNA binding GO:0003677 9.76 SUPV3L1 RTEL1 PIF1 DHX36
2 hydrolase activity GO:0016787 9.72 SUPV3L1 RTEL1 PIF1 HFM1 DHX36
3 ATP binding GO:0005524 9.65 SUPV3L1 RTEL1 PIF1 HFM1 DHX36
4 nucleic acid binding GO:0003676 9.61 RTEL1 HFM1 DHX36
5 RNA helicase activity GO:0003724 9.4 SUPV3L1 DHX36
6 double-stranded RNA binding GO:0003725 9.37 SUPV3L1 DHX36
7 helicase activity GO:0004386 9.35 SUPV3L1 RTEL1 PIF1 HFM1 DHX36
8 G-quadruplex DNA binding GO:0051880 9.16 PIF1 DHX36
9 DNA helicase activity GO:0003678 9.02 SUPV3L1 RTEL1 PIF1 HFM1 DHX36

Sources for Dyskeratosis Congenita, Autosomal Recessive 5

3 CDC
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11 DGIdb
17 EFO
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68 SNOMED-CT via HPO
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