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

Roberto Valli, Antonella Minelli, Marta Galbiati, Giovanna D'Amico, Annalisa Frattini, Giuseppe Montalbano, Abdul W Khan, Giovanni Porta, Giorgia Millefanti, Carla Olivieri, Marco Cipolli, Simone Cesaro, Francesco Pasquali, Cesare Danesino, Gianni Cazzaniga, Emanuela Maserati

Research output: Contribution to journalArticle

Abstract

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 EIF6 gene. The genes L3MBTL1 and SGK2, 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 EIF6 gene. Interestingly, array single nucleotide polymorphisms (SNPs) showed copy neutral loss of heterozygosity for EIF6 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 EIF6 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).
Original languageEnglish
Pages (from-to)974-981
Number of pages8
JournalBritish Journal of Haematology
Volume184
Issue number6
DOIs
Publication statusPublished - Mar 2019

Keywords

  • *EIF6 gene
  • *Shwachman Diamond syndrome
  • *del(20)(q)
  • *genomic instability
  • *risk of MDS/AML/BM aplasia

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    Valli, R., Minelli, A., Galbiati, M., D'Amico, G., Frattini, A., Montalbano, G., Khan, A. W., Porta, G., Millefanti, G., Olivieri, C., Cipolli, M., Cesaro, S., Pasquali, F., Danesino, C., Cazzaniga, G., & Maserati, E. (2019). Shwachman-Diamond syndrome with clonal interstitial deletion of the long arm of chromosome 20 in bone marrow: haematological features, prognosis and genomic instability. British Journal of Haematology, 184(6), 974-981. https://doi.org/10.1111/bjh.15729