Abnormal telomere shortening in leucocytes of children with Shwachman-Diamond syndrome.

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.