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. 2004 Jun;45(1-2):13–22. doi: 10.1007/s10616-004-5121-5

Telomerase dysfunction and dyskeratosis congenita

Amanda J Walne 1,✉, Inderjeet Dokal 1
PMCID: PMC3449960  PMID: 19003239

Abstract

Dyskeratosis congenita (DC) is a multi system bone marrow failure syndrome characterized by muco-cutaneous abnormalities and an increased predisposition to malignancy. It exhibits considerable clinical and genetic heterogeneity. X-linked recessive, autosomal dominant and autosomal recessive forms of the disease are recognized. The X-linked recessive form is due to mutations in dyskerin, which is a component of both small nucleolar ribonuclear protein particles and the telomerase complex. Autosomal dominant DC is due to mutations in the RNA component of telomerase, TERC. As dyskerin and TERC are both components of the telomerase complex and all patients with DC have short telomeres it appears that the principal pathology in DC relates to telomerase dysfunction. The gene or genes involved in the recessive form of DC remain elusive, though genes whose products are required for telomere maintenance remain strong candidates. The study of DC has highlighted the critical role of telomerase and the consequences, including premature aging and malignancy, of its dysfunction.

Keywords: Dyskeratosis congenita, Dyskerin, Telomerase, Telomere, TERC

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Glossary

AA

aplastic anaemia

CR4-CR5 domain

conserved region 4 and conserved region 5

CR7

conserved region 7

DC

dyskeratosis congenita

DCR

dyskeratosis congenita registry

DKC1

dyskeratosis congenita gene 1-mutated in X-linked DC

Dkc1

mouse homologue of DKC1

GAR1

glycine-arginine-rich protein 1

H/ACA domain

hairpin-hinge-hairpin-ACA motif

HH

Hoyeraal–Hreidarsson syndrome

IVS

intervening sequence

MDS

myelodysplastic syndrome

NOP10

novel protein 10Kd

NHP2

novel high mobility group (HMG)- like protein 2

rRNA

ribosomal RNA

RNP

ribonucleoprotein

SnoRNAs

small nucleolar RNA

SnoRNP

small nucleolar ribonucleoprotein

Terc

mouse homologue of TERC

hTERT

telomerase reverse transcriptase (human)

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