KEGG DISEASE: Dyskeratosis congenita

DISEASE: Dyskeratosis congenita

Entry

H00507                      Disease

Name

Dyskeratosis congenita

Subgroup

X-linked dyskeratosis congenita (DKCX) [DS:H00788]
Autosomal dominant dyskeratosis congenita (DKCA)
Autosomal recessive dyskeratosis congenita (DKCB)
Digenic dyskeratosis congenita (DKCD)
Revesz syndrome [DS:H00921]

Description

Dyskeratosis congenita (DC) is a severe inherited bone marrow failure syndrome with associated cutaneous and noncutaneous abnormalities. In most cases, the inheritance pattern is X-linked recessive, while autosomal dominant and autosomal recessive forms have been reported. Remarkably, all causative gene mutations identified to date share a link to telomere/telomerase biology. Moreover, dyskeratosis congenita is linked to defective ribosome biogenesis.

Category

Ribosomopathy

Brite

Human diseases in ICD-11 classification [BR:br08403]
03 Diseases of the blood or blood-forming organs
  Anaemias or other erythrocyte disorders
   3A70  Aplastic anaemia
    H00507  Dyskeratosis congenita
Pathway-based classification of diseases [BR:br08402]
Replication and repair
  nt06510  Telomere length regulation
   H00507  Dyskeratosis congenita
  nt06506  Double-strand break repair
   H00507  Dyskeratosis congenita

Pathway

hsa03008

Ribosome biogenesis in eukaryotes

Network

nt06506 Double-strand break repair
nt06510 Telomere length regulation

Gene

(DKCX) DKC1 [HSA:1736] [KO:K11131]
(DKCA1) TERC [HSA:7012] [KO:K22183]
(DKCA2/B4) TERT [HSA:7015] [KO:K11126]
(DKCA3/A5) TINF2 [HSA:26277] [KO:K11112]
(DKCA4/B5) RTEL1 [HSA:51750] [KO:K11136]
(DKCA6/B7) ACD [HSA:65057] [KO:K11114]
(DKCB1) NOP10 [HSA:55505] [KO:K11130]
(DKCB2) NHP2 [HSA:55651] [KO:K11129]
(DKCB3) WRAP53 [HSA:55135] [KO:K23314]
(DKCB6) PARN [HSA:5073] [KO:K01148]
(DKCB8) DCLRE1B [HSA:64858] [KO:K15341]
(DKCD) TYMS [HSA:7298] [KO:K00560]

Other DBs

ICD-11:

3A70.0

MeSH:

D019871

OMIM:

305000 127550 613989 613990 615190 616553 224230 613987 613988 616353 620133 620040

Reference

PMID:18005359

Authors

Kirwan M, Dokal I

Title

Dyskeratosis congenita: a genetic disorder of many faces.

Journal

Clin Genet 73:103-12 (2008)
DOI:10.1111/j.1399-0004.2007.00923.x

Reference

PMID:9590285 (DKCX)

Authors

Heiss NS, Knight SW, Vulliamy TJ, Klauck SM, Wiemann S, Mason PJ, Poustka A, Dokal I

Title

X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions.

Journal

Nat Genet 19:32-8 (1998)
DOI:10.1038/ng0598-32

Reference

PMID:11574891 (DKCA1)

Authors

Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I

Title

The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita.

Journal

Nature 413:432-5 (2001)
DOI:10.1038/35096585

Reference

PMID:18460650 (DKCA2)

Authors

Basel-Vanagaite L, Dokal I, Tamary H, Avigdor A, Garty BZ, Volkov A, Vulliamy T

Title

Expanding the clinical phenotype of autosomal dominant dyskeratosis congenita caused by TERT mutations.

Journal

Haematologica 93:943-4 (2008)
DOI:10.3324/haematol.12317

Reference

PMID:21477109 (DKCA3 DKCA5)

Authors

Sasa GS, Ribes-Zamora A, Nelson ND, Bertuch AA

Title

Three novel truncating TINF2 mutations causing severe dyskeratosis congenita in early childhood.

Journal

Clin Genet 81:470-8 (2012)
DOI:10.1111/j.1399-0004.2011.01658.x

Reference

PMID:23329068 (DKCA4 DKCB5)

Authors

Ballew BJ, Yeager M, Jacobs K, Giri N, Boland J, Burdett L, Alter BP, Savage SA

Title

Germline mutations of regulator of telomere elongation helicase 1, RTEL1, in Dyskeratosis congenita.

Journal

Hum Genet 132:473-80 (2013)
DOI:10.1007/s00439-013-1265-8

Reference

PMID:25205116 (DKCA6)

Authors

Guo Y, Kartawinata M, Li J, Pickett HA, Teo J, Kilo T, Barbaro PM, Keating B, Chen Y, Tian L, Al-Odaib A, Reddel RR, Christodoulou J, Xu X, Hakonarson H, Bryan TM

Title

Inherited bone marrow failure associated with germline mutation of ACD, the gene encoding telomere protein TPP1.

Journal

Blood 124:2767-74 (2014)
DOI:10.1182/blood-2014-08-596445

Reference

PMID:17507419 (DKCB1)

Authors

Walne AJ, Vulliamy T, Marrone A, Beswick R, Kirwan M, Masunari Y, Al-Qurashi FH, Aljurf M, Dokal I

Title

Genetic heterogeneity in autosomal recessive dyskeratosis congenita with one subtype due to mutations in the telomerase-associated protein NOP10.

Journal

Hum Mol Genet 16:1619-29 (2007)
DOI:10.1093/hmg/ddm111

Reference

PMID:18523010 (DKCB2)

Authors

Vulliamy T, Beswick R, Kirwan M, Marrone A, Digweed M, Walne A, Dokal I

Title

Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita.

Journal

Proc Natl Acad Sci U S A 105:8073-8 (2008)
DOI:10.1073/pnas.0800042105

Reference

PMID:21205863 (DKCB3)

Authors

Zhong F, Savage SA, Shkreli M, Giri N, Jessop L, Myers T, Chen R, Alter BP, Artandi SE

Title

Disruption of telomerase trafficking by TCAB1 mutation causes dyskeratosis congenita.

Journal

Genes Dev 25:11-6 (2011)
DOI:10.1101/gad.2006411

Reference

PMID:17785587 (DKCB4)

Authors

Marrone A, Walne A, Tamary H, Masunari Y, Kirwan M, Beswick R, Vulliamy T, Dokal I

Title

Telomerase reverse-transcriptase homozygous mutations in autosomal recessive dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome.

Journal

Blood 110:4198-205 (2007)
DOI:10.1182/blood-2006-12-062851

Reference

PMID:26342108 (DKCB6)

Authors

Dhanraj S, Gunja SM, Deveau AP, Nissbeck M, Boonyawat B, Coombs AJ, Renieri A, Mucciolo M, Marozza A, Buoni S, Turner L, Li H, Jarrar A, Sabanayagam M, Kirby M, Shago M, Pinto D, Berman JN, Scherer SW, Virtanen A, Dror Y

Title

Bone marrow failure and developmental delay caused by mutations in poly(A)-specific ribonuclease (PARN).

Journal

J Med Genet 52:738-48 (2015)
DOI:10.1136/jmedgenet-2015-103292

Reference

PMID:25233904 (DKCB7)

Authors

Kocak H, Ballew BJ, Bisht K, Eggebeen R, Hicks BD, Suman S, O'Neil A, Giri N, Maillard I, Alter BP, Keegan CE, Nandakumar J, Savage SA

Title

Hoyeraal-Hreidarsson syndrome caused by a germline mutation in the TEL patch of the telomere protein TPP1.

Journal

Genes Dev 28:2090-102 (2014)
DOI:10.1101/gad.248567.114

Reference

PMID:35007328 (DKCB8)

Authors

Kermasson L, Churikov D, Awad A, Smoom R, Lainey E, Touzot F, Audebert-Bellanger S, Haro S, Roger L, Costa E, Mouf M, Bottero A, Oleastro M, Abdo C, de Villartay JP, Geli V, Tzfati Y, Callebaut I, Danielian S, Soares G, Kannengiesser C, Revy P

Title

Inherited human Apollo deficiency causes severe bone marrow failure and developmental defects.

Journal

Blood 139:2427-2440 (2022)
DOI:10.1182/blood.2021010791

Reference

PMID:35931051 (DKCD)

Authors

Tummala H, Walne A, Buccafusca R, Alnajar J, Szabo A, Robinson P, McConkie-Rosell A, Wilson M, Crowley S, Kinsler V, Ewins AM, Madapura PM, Patel M, Pontikos N, Codd V, Vulliamy T, Dokal I

Title

Germline thymidylate synthase deficiency impacts nucleotide metabolism and causes dyskeratosis congenita.

Journal

Am J Hum Genet 109:1472-1483 (2022)
DOI:10.1016/j.ajhg.2022.06.014

LinkDB

» Japanese version

DISEASE: Pulmonary fibrosis and/or bone marrow failure, telomere-related

Entry

H02569                      Disease

Name

Pulmonary fibrosis and/or bone marrow failure, telomere-related

Supergrp

Idiopathic pulmonary fibrosis [DS:H01299]

Description

Pulmonary fibrosis and/or bone marrow failure, telomere-related (PFBMFT) is also known as human telomere biology disorders, or short telomere syndromes. PFBMFT is a group of hereditary disorders caused by inherited loss-of-function mutations in telomere associated genes. It has a wide phenotypic spectrum that include bone marrow failure, pulmonary and liver fibrosis, mucocutaneous fragility, and predisposition to myelodysplastic syndromes and cancer.

Category

Hematologic disease

Brite

Human diseases in ICD-11 classification [BR:br08403]
03 Diseases of the blood or blood-forming organs
  Anaemias or other erythrocyte disorders
   3A70  Aplastic anaemia
    H02569  Pulmonary fibrosis and/or bone marrow failure, telomere-related
Pathway-based classification of diseases [BR:br08402]
Replication and repair
  nt06509  DNA replication
   H02569  Pulmonary fibrosis and/or bone marrow failure, telomere-related
  nt06510  Telomere length regulation
   H02569  Pulmonary fibrosis and/or bone marrow failure, telomere-related
  nt06502  Nucleotide excision repair
   H02569  Pulmonary fibrosis and/or bone marrow failure, telomere-related
  nt06506  Double-strand break repair
   H02569  Pulmonary fibrosis and/or bone marrow failure, telomere-related
  nt06508  Interstrand crosslink repair
   H02569  Pulmonary fibrosis and/or bone marrow failure, telomere-related

Pathway

hsa03420 Nucleotide excision repair

Network

nt06502 Nucleotide excision repair
nt06506 Double-strand break repair
nt06508 Interstrand crosslink repair
nt06509 DNA replication
nt06510 Telomere length regulation

Gene

(PFBMFT1) TERT [HSA:7015] [KO:K11126]
(PFBMFT2) TERC [HSA:7012] [KO:K22183]
(PFBMFT3) RTEL1 [HSA:51750] [KO:K11136]
(PFBMFT4) PARN [HSA:5073] [KO:K01148]
(PFBMFT5) ZCCHC8 [HSA:55596] [KO:K13128]
(PFBMFT6) RPA1 [HSA:6117] [KO:K07466]
(PFBMFT7) NAF1 [HSA:92345] [KO:K14763]
(PFBMFT8) POT1 [HSA:25913] [KO:K11109]
(PFBMFT9) NOP10 [HSA:55505] [KO:K11130]

Other DBs

ICD-11:

3A70.0

OMIM:

614742 614743 616373 616371 618674 619767 620365 620367 620400

Reference

PMID:22512499

Authors

Gansner JM, Rosas IO, Ebert BL

Title

Pulmonary fibrosis, bone marrow failure, and telomerase mutation.

Journal

N Engl J Med 366:1551-3 (2012)
DOI:10.1056/NEJMc1200999

Reference

PMID:15814878 (PFBMFT1)

Authors

Yamaguchi H, Calado RT, Ly H, Kajigaya S, Baerlocher GM, Chanock SJ, Lansdorp PM, Young NS

Title

Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia.

Journal

N Engl J Med 352:1413-24 (2005)
DOI:10.1056/NEJMoa042980

Reference

PMID:12090986 (PFBMFT2)

Authors

Vulliamy T, Marrone A, Dokal I, Mason PJ

Title

Association between aplastic anaemia and mutations in telomerase RNA.

Journal

Lancet 359:2168-70 (2002)
DOI:10.1016/S0140-6736(02)09087-6

Reference

PMID:25848748 (PFBMFT3 PFBMFT4)

Authors

Stuart BD, Choi J, Zaidi S, Xing C, Holohan B, Chen R, Choi M, Dharwadkar P, Torres F, Girod CE, Weissler J, Fitzgerald J, Kershaw C, Klesney-Tait J, Mageto Y, Shay JW, Ji W, Bilguvar K, Mane S, Lifton RP, Garcia CK

Title

Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening.

Journal

Nat Genet 47:512-7 (2015)
DOI:10.1038/ng.3278

Reference

PMID:31488579 (PFBMFT5)

Authors

Gable DL, Gaysinskaya V, Atik CC, Talbot CC Jr, Kang B, Stanley SE, Pugh EW, Amat-Codina N, Schenk KM, Arcasoy MO, Brayton C, Florea L, Armanios M

Title

ZCCHC8, the nuclear exosome targeting component, is mutated in familial pulmonary fibrosis and is required for telomerase RNA maturation.

Journal

Genes Dev 33:1381-1396 (2019)
DOI:10.1101/gad.326785.119

Reference

PMID:34767620 (PFBMFT6)

Authors

Sharma R, Sahoo SS, Honda M, Granger SL, Goodings C, Sanchez L, Kunstner A, Busch H, Beier F, Pruett-Miller SM, Valentine MB, Fernandez AG, Chang TC, Geli V, Churikov D, Hirschi S, Pastor VB, Boerries M, Lauten M, Kelaidi C, Cooper MA, Nicholas S, Rosenfeld JA, Polychronopoulou S, Kannengiesser C, Saintome C, Niemeyer CM, Revy P, Wold MS, Spies M, Erlacher M, Coulon S, Wlodarski MW

Title

Gain-of-function mutations in RPA1 cause a syndrome with short telomeres and somatic genetic rescue.

Journal

Blood 139:1039-1051 (2022)
DOI:10.1182/blood.2021011980

Reference

PMID:27510903 (PFBMFT7)

Authors

Stanley SE, Gable DL, Wagner CL, Carlile TM, Hanumanthu VS, Podlevsky JD, Khalil SE, DeZern AE, Rojas-Duran MF, Applegate CD, Alder JK, Parry EM, Gilbert WV, Armanios M

Title

Loss-of-function mutations in the RNA biogenesis factor NAF1 predispose to pulmonary fibrosis-emphysema.

Journal

Sci Transl Med 8:351ra107 (2016)
DOI:10.1126/scitranslmed.aaf7837

Reference

PMID:35420632 (PFBMFT8)

Authors

Kelich J, Aramburu T, van der Vis JJ, Showe L, Kossenkov A, van der Smagt J, Massink M, Schoemaker A, Hennekam E, Veltkamp M, van Moorsel CHM, Skordalakes E

Title

Telomere dysfunction implicates POT1 in patients with idiopathic pulmonary fibrosis.

Journal

J Exp Med 219:213140 (2022)
DOI:10.1084/jem.20211681

Reference

PMID:32139460 (PFBMFT9)

Authors

Kannengiesser C, Manali ED, Revy P, Callebaut I, Ba I, Borgel A, Oudin C, Haritou A, Kolilekas L, Malagari K, Borie R, Lainey E, Boileau C, Crestani B, Papiris SA

Title

First heterozygous NOP10 mutation in familial pulmonary fibrosis.

Journal

Eur Respir J 55:1902465 (2020)
DOI:10.1183/13993003.02465-2019

LinkDB

» Japanese version

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