Clinical spectrum and molecular pathophysiology of Shwachman-Diamond syndrome.
OBJECTIVE
Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure and cancer predisposition syndrome that affects multiple organ systems. Mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene are found in the majority of patients, but the molecular function of the SBDS protein product remains unclear. In this article, we review recent progress in the clinical and molecular characterization of SDS.


RESULTS
Emerging data support a multifunctional role for the SBDS protein. Current studies indicate that SBDS functions in 60S large ribosomal subunit maturation and in mitotic spindle stabilization. Recent data suggest that it may also affect actin polymerization, vacuolar pH regulation, and DNA metabolism. SBDS loss results in both hematopoietic cell-intrinsic defects as well as marrow stromal abnormalities.


CONCLUSIONS
SDS is a multisystemic disease arising from defects in a protein that participates in several essential cellular processes. Elucidating the molecular function of SBDS will provide important insights into how defects in ribosome biogenesis and mitotic spindle stabilization result in hematopoietic failure, cancer predisposition, and abnormalities.
aThe University of California, San Francisco School of Medicine and UCSF Benioff Children's Hospital, San Francisco, CA, USA bFred Hutchinson Cancer Research Center, Seattle Children's Hospital and University of Washington, Seattle, WA, USA.
James N
JN
Huang
Akiko
A
Shimamura
D001855:Bone Marrow Diseases / Q000175:diagnosis* / Q000209:etiology*; D018450:Disease Progression; D010188:Exocrine Pancreatic Insufficiency / Q000175:diagnosis* / Q000209:etiology*; D006801:Humans; D008068:Lipomatosis / Q000175:diagnosis* / Q000209:etiology*; D000081003:Shwachman-Diamond Syndrome