Shwachman-Diamond Syndrome: Molecular Mechanisms and Current Perspectives

Mol Diagn Ther. 2019 Apr;23(2):281-290. doi: 10.1007/s40291-018-0368-2.


Shwachman-Diamond syndrome (SDS) is a rare inherited disease mainly caused by mutations in the Shwachman-Bodian-Diamond Syndrome (SBDS) gene. However, it has recently been reported that other genes, including DnaJ heat shock protein family (Hsp40) member C21 (DNAJC21), elongation factor-like 1 (EFL1) and signal recognition particle 54 (SRP54) are also associated with an SDS-like phenotype. Interestingly, SBDS, DNAJC21, EFL1 and SRP54 are involved in ribosome biogenesis: SBDS, through direct interaction with EFL1, promotes the release of the eukaryotic initiation factor 6 (eIF6) during ribosome maturation, DNAJC21 stabilizes the 80S ribosome, and SRP54 facilitates protein trafficking. These findings strengthen the postulate that SDS is a ribosomopathy. SDS is a multiple-organ disease mainly characterized by bone marrow failure, bone malformations, pancreatic insufficiency and cognitive disorders. Almost 15-20% of patients with SDS present myelodysplastic syndrome with a high risk of acute myeloid leukemia (AML) transformation. Unfortunately, besides bone marrow transplantation, no gene-based therapy for SDS has yet been developed. This review aims to recapitulate the recent findings on the molecular mechanisms of SDS underlying bone marrow failure, hematopoiesis and AML development and to draw a realistic picture of current perspectives.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone Marrow Diseases / diagnosis
  • Bone Marrow Diseases / genetics*
  • Bone Marrow Diseases / therapy
  • Disease Models, Animal
  • Exocrine Pancreatic Insufficiency / diagnosis
  • Exocrine Pancreatic Insufficiency / genetics*
  • Exocrine Pancreatic Insufficiency / therapy
  • Hematopoiesis / genetics
  • Humans
  • Lipomatosis / diagnosis
  • Lipomatosis / genetics*
  • Lipomatosis / therapy
  • Mutation / genetics
  • Shwachman-Diamond Syndrome