title: Abnormal telomere shortening in leucocytes of children with Shwachman-Diamond syndrome.
abstract: Haemopoietic dysfunction, ranging from single-lineage cytopenia to severe aplasia and/or myelodysplasia (MDS), is prominent in Shwachman-Diamond syndrome (SDS). To assess haemopoietic stem cell proliferation in SDS, we compared leucocyte telomere length in 12 patients with SDS to that of 41 controls, using an in-gel hybridization technique. SDS patients had an age-adjusted mean telomere length 1.4 kilobase pairs (kbp) shorter than controls (P < 0.0001). Patients with'non-severe' SDS (one- or two-lineage cytopenias; no MDS) had shortened telomeres (-1.4 kbp; P = 0.0004), as did those with 'severe' SDS. We conclude that stem cell hyperproliferation is a feature of SDS from its outset.
authors.affiliation: Division of Haematology/Oncology, The Hospital for Sick Children, University of Toronto, Ontario, Canada.
authors.forename: Ian
authors.initials: I
authors.lastname: Thornley
authors.forename: Yigal
authors.initials: Y
authors.lastname: Dror
authors.forename: Lilian
authors.initials: L
authors.lastname: Sung
authors.forename: Rob F
authors.initials: RF
authors.lastname: Wynn
authors.forename: Melvin H
authors.initials: MH
authors.lastname: Freedman
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D005260:Female; D006402:Hematologic Diseases / Q000209:etiology* / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000648:ultrastructure*; D006801:Humans; D007223:Infant; D016018:Least-Squares Analysis; D007962:Leukocytes / Q000648:ultrastructure*; D008297:Male; D016615:Telomere / Q000648:ultrastructure*