title: Dyskeratosis congenita: its link to telomerase and aplastic anaemia.
abstract: Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome exhibiting considerable clinical and genetic heterogeneity. X-linked recessive, autosomal dominant and autosomal recessive forms are recognised. The gene mutated in X-linked DC (DKC1) encodes a highly conserved nucleolar protein called dyskerin. Dyskerin associates with the H/ACA class of small nucleolar RNAs which are important in guiding the conversion of uracil to pseudouracil in ribosomal RNA. Dyskerin also associates with the RNA component of telomerase (hTR) which is important in the maintenance of telomeres. Mutations in hTR were recently demonstrated in patients with autosomal dominant DC and in a subset of patients with aplastic anaemia (AA) but without other diagnostic features of DC. This discovery demonstrates that both DC and a subset of AA are due to a defect in telomerase. The link between DC and AA and in turn to defective telomerase suggests that treatments directed at correction of telomerase activity might benefit DC/AA patients who do not respond to conventional therapy.
authors.affiliation: Department of Haematology-Division of Investigative Science, Faculty of Medicine, Imperial College, Hammersmith Hospital, Commonwealth Building, London, UK. i.dokal@ic.ac.uk
authors.forename: Inderjeet
authors.initials: I
authors.lastname: Dokal
authors.forename: Tom
authors.initials: T
authors.lastname: Vulliamy
mesh_terms: D000741:Anemia, Aplastic / Q000209:etiology / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002874:Chromosome Mapping; D019871:Dyskeratosis Congenita / Q000209:etiology / Q000235:genetics*; D005192:Family Health; D006801:Humans; D040582:Inheritance Patterns; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C112148:DKC1 protein, human; D009687:Nuclear Proteins; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase