Document Detail

Dyskeratosis congenita: advances in the understanding of the telomerase defect and the role of stem cell transplantation.
MedLine Citation:
PMID:  17663679     Owner:  NLM     Status:  MEDLINE    
DC is a multisystem bone marrow failure syndrome exhibiting marked clinical and genetic heterogeneity. X-linked, autosomal dominant and autosomal recessive subtypes are recognized. The gene mutated in X-linked DC (DKC1) encodes a highly conserved nucleolar protein called dyskerin. Dyskerin associates with the H/ACA motif class of small nucleolar RNAs in small nucleolar ribonucleoprotein particles that are important in guiding the conversion of uracil to pseudouracil during the maturation of ribosomal RNA. Dyskerin also associates with the TERC, which is important in the maintenance of telomeres. Mutations in TERC have been identified in patients with autosomal dominant DC and in a subset of patients with aplastic anemia and myelodysplasia. Recently, heterozygous mutations in TERT have been found in some patients with autosomal dominant DC and aplastic anemia. Additionally, patients with the severe multisystem disorder, Hoyeraal-Hreidarsson syndrome, have been found to have DKC1 mutations. Collectively, these observations have demonstrated that classical DC, Hoyeraal-Hreidarsson syndrome and a subset of aplastic anemia are due to a primary defect in telomerase. The critical role of telomeres and telomerase in humans is seen in the multisystem abnormalities found in these patients, including the increased incidence of malignancy. As bone marrow failure is the principal cause of death, conventional allografts have been attempted with limited success due to the high rate of pulmonary and endothelial complications. However, outcomes have improved with the use of non-myeloablative protocols, although the follow up is too short to evaluate long term toxicity and the natural course of the disease and it may be that correction of the telomerase defect is essential for the treatment of these patients.
Josu de la Fuente; Inderjeet Dokal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pediatric transplantation     Volume:  11     ISSN:  1397-3142     ISO Abbreviation:  Pediatr Transplant     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-07-31     Completed Date:  2007-10-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9802574     Medline TA:  Pediatr Transplant     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  584-94     Citation Subset:  IM    
Department of Paediatrics, St. Mary's Hospital, and Academic Unit of Paediatrics, Institute of Cell and Molecular Science, Barts and The London, Queen Mary's Schoo of Medicine and Dentistry, UK.
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MeSH Terms
Cell Cycle Proteins / genetics*
Child, Preschool
Dyskeratosis Congenita / genetics*,  surgery*
Nuclear Proteins / genetics*
Stem Cell Transplantation*
Telomerase / genetics*
Grant Support
//Wellcome Trust
Reg. No./Substance:
0/Cell Cycle Proteins; 0/DKC1 protein, human; 0/Nuclear Proteins; EC protein, human; EC

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