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Dyskeratosis congenita: molecular insights into telomerase function, ageing and cancer

Published online by Cambridge University Press:  21 December 2004

Anna Marrone
Affiliation:
Department of Haematology, Division of Investigative Science, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.
Inderjeet Dokal
Affiliation:
Department of Haematology, Division of Investigative Science, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.

Abstract

Dyskeratosis congenita (DC) is a severe, inherited, bone marrow failure syndrome, with associated cutaneous and noncutaneous abnormalities. DC patients also show signs of premature ageing and have an increased occurrence of cancer. DC can originate through: (1) mutations in DKC1, which result in X-linked recessive DC; (2) mutations in the RNA component of telomerase (TERC), which result in autosomal dominant DC (AD-DC); and (3) mutations in other, currently uncharacterised, genes, which result in autosomal recessive DC (AR-DC). As DKC1 encodes dyskerin, a protein component of small nucleolar ribonucleoprotein (snoRNP) particles, which are important in ribosomal RNA processing, DC was initially described as a disorder of defective ribosomal biogenesis. Subsequently, dyskerin and TERC were shown to closely associate with each other in the telomerase complex, and DC has since come to be regarded as a telomerase deficiency disorder characterised by shorter telomeres. These findings demonstrate the importance of telomerase in humans and highlight how its deficiency (through DKC1 and TERC mutations) results in multiple abnormalities including premature ageing, bone marrow failure and cancer. Identification of the gene(s) involved in AR-DC will help to define the pathophysiology of DC further, as well as expand our insights into telomere function, ageing and cancer.

Type
Review Article
Copyright
© Cambridge University Press 2004

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