90% of patients have biallelic mutations in the SBDS gene (encoding a 250 amino acid protein)
SBDS protein is a gatekeeper performing quality control for ribosome formation
SBDS protein couples the final step in cytoplasmic maturation of the large (60S) ribosomal subunit to a quality control assessment of the structural and functional integrity of the nascent particle.
SBDS functions as a cofactor for elongation factor-like GTPase 1 (EFL1) in removing the anti-association factor eIF6 from the subunit joining face of the 60S ribosomal subunit
Source: Warren, A.J., Molecular basis of the human ribosomopathy Shwachman Diamond syndrome, Advances in Biological Regulation (2017), http://dx.doi.org/10.1016/j.jbior.2017.09.002
Variable Clinical Presentation of Shwachman Diamond Syndrome: Update from the North American Shwachman–Diamond Syndrome Registry, Kasiani C. Myers, MD, Audrey Anna Bolyard, RN, BS, Barbara Otto, MN, MS, Trisha E. Wong, MD, MS, Amanda T. Jones, Richard E. Harris, MD, Stella M. Davies, MBBS, PhD, David C. Dale, MD, and Akiko Shimamura, MD, PhD, 2013