Shwachman‐Diamond syndrome with clonal interstitial deletion of the long arm of chromosome 20 in bone marrow: haematological features, prognosis and genomic instability

Summary In Shwachman‐Diamond syndrome ( SDS ), deletion of the long arm of chromosome 20, del(20)(q), often acquired in bone marrow ( BM ), may imply a lower risk of developing myelodysplastic syndrome/acute myeloid leukaemia ( MDS / AML ), due to the loss of the EIF 6 gene. The genes L3 MBTL 1 and SGK 2 , also on chromosome 20, are in a cluster of imprinted genes, and their loss implies dysregulation of BM function. We report here the results of array comparative genomic hybridization (a‐ CGH ) performed on BM DNA of six patients which confirmed the consistent loss of EIF 6 gene. Interestingly, array single nucleotide polymorphisms ( SNP s) showed copy neutral loss of heterozygosity for EIF 6 region in cases without del(20)(q). No preferential parental origin of the deleted chromosome 20 was detected by microsatellite analysis in six SDS patients. Our patients showed a very mild haematological condition, and none evolved into BM aplasia or MDS / AML . We extend the benign prognostic significance of del(20)(q) and loss of EIF 6 to the haematological features of these patients, consistently characterized by mild hypoplastic BM , no or mild neutropenia, anaemia and thrombocytopenia. Some odd results obtained in microsatellite and SNP ‐array analysis demonstrate a peculiar genomic instability, in an attempt to improve BM function through the acquisition of the del(20)(q).