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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