title: Low frequency of telomerase RNA mutations among children with aplastic anemia or myelodysplastic syndrome.
abstract: Mutations in TERC, the RNA component of telomerase, result in autosomal dominant dyskeratosis congenita (DC), a rare bone marrow failure syndrome. TERC mutations have been detected in a subset of patients previously diagnosed with aplastic anemia and myelodysplastic syndrome (MDS), and these TERC mutations are clinically relevant as patients with DC respond poorly to conventional therapies. We aimed to determine the frequency of TERC mutations in pediatric patients with aplastic anemia and MDS who required a hematopoietic stem cell transplant. We obtained 284 blood samples from the National Donor Marrow Program Research Sample Repository from children and adolescents with bone marrow failure who underwent an unrelated stem cell transplant. We screened these samples for mutations in the TERC gene using direct DNA sequencing. We found 2 patients with sequence alterations in TERC. We identified a 2 base pair deletion (-240delCT) in a 4-year-old child with MDS and a single nucleotide alteration (-99-->CG) in a 1-year-old child with juvenile myelomonocytic leukemia. Screening for TERC gene mutations is unlikely to diagnose occult DC in children with severe bone marrow failure who require a hematopoietic stem cell transplant.
authors.affiliation: Department of Pathology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Field
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mason
authors.forename: Ping
authors.initials: P
authors.lastname: An
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kasai
authors.forename: Michael
authors.initials: M
authors.lastname: McLellan
authors.forename: Sara
authors.initials: S
authors.lastname: Jaeger
authors.forename: Yvonne J
authors.initials: YJ
authors.lastname: Barnes
authors.forename: Allison A
authors.initials: AA
authors.lastname: King
authors.forename: Monica
authors.initials: M
authors.lastname: Bessler
authors.forename: David B
authors.initials: DB
authors.lastname: Wilson
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000235:genetics* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis / Q000379:methods; D019871:Dyskeratosis Congenita / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D014644:Genetic Variation; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics* / Q000628:therapy; D008297:Male; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000628:therapy; D017354:Point Mutation; D012313:RNA / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D014184:Transplantation, Homologous
chemical_list: C422952:telomerase RNA; D012313:RNA; D019098:Telomerase