SDS & Science Snapshots (2023-11-11)

In this issue: Two new publications by Dr. Seth Corey's group. One comparing genes associated with SDS-like syndrome, and the other on their recent work on zebrafish.

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email connect@SDSAlliance.org or message us on Facebook! This is all for you!

New review article by Dr. Corey:

Shwachman-Diamond syndromes: clinical, genetic, and biochemical insights from the rare variants

The gene that causes SDS in over 90 of patients is the SBDS gene, but other genes have been associated with SDS or SDS-like syndromes as well. The experts have not yet agreed on whether these genes should be considered SDS causing, or rather causing similar but distinct SDS-like syndromes. Dr. Corey's review article is highlighting commonalities on the genes EFL1, DNAJC21, and SRP54 when it comes to symptoms and where they fit into the overall pathways of ribosome and protein maturation.

Image and captions from https://haematologica.org/article/view/haematol.2023.282949: Components of the Shwachman-Diamond syndrome pathway participate in ribosomal biosynthesis and initial escort by the signal recognition particle. Ribosome maturation begins in the nucleus with the formation of the pre-60S and pre-40S subunits. These subunits traffic through the nuclear pores to the cytosol where the final steps of ribosome maturation occur, forming the 80S ready for translation of mRNA into a nascent polypeptide. The polypeptide emerges from the ribosome and is further processed via the signal recognition particle. See original article for further details.

BDS, EFL1, DNAJC21, and SRP54 encode proteins involved in ribosome assembly and nascent polypeptide synthesis. SDS has been viewed as a ribosomopathy. This term has been applied to diverse diseases with germline or somatic mutations, such as Treacher Collins syndrome, DiamondBlackfan anemia, cartilage hair hypoplasia, and del(5q) MDS.

The authors "suggest using the term Shwachman-Diamond syndromes or Shwachman-Diamond-like syndrome to denote disorders that may involve blood and/or pancreatic abnormalities, and which result from germline variants that encode proteins affecting ribosome biogenesis and early protein synthesis. The term Diamond-Blackfan anemia should be reserved for those with congenital hypoplastic anemia."

The full article is available free (open access):

Access the full original article here

Shwachman-Diamond syndromes: clinical, genetic, and biochemical insights from the rare variants.

Kawashima N, Oyarbide U, Cipolli M, Bezzerri V, Corey SJ.

Haematologica. 2023 Oct 1;108(10):2594-2605.

doi: 10.3324/haematol.2023.282949.

PMID: 37226705

New publication by Dr. Corey's group: SBDSR126T rescues survival of sbds−/− zebrafish in a dose-dependent manner independently of Tp53

In this new article, the research team is using their zebrafish model in which the SBDS gene has been deleted. They re-introduce various amounts of functional SBDS protein using genetic tools. The results show that the more functional SBDS protein there is, the better the fish model develops and survives; and that this phenomenon is independent of Tp53.

This figure shows a summary of the work. The bottom row are zebrafish embryos that don't have any or enough functional SBDS protein, and therefore cannot develop beyond the early embryo stage. The top row depicts zebrafish that has the normal amount of SBDS protein and therefore develops normally. The rows in the model summarize what happens when there is less than normal amount of SBDS protein or if p53 signaling is disrupted.