SDS & Science Snapshots (2022-03-20)

In this issue: Report of a new variant in DNAJC21 associated with SDS like symptoms; Plus, new FDA Guidance on Patient-Focused Drug Development

Welcome to our weekly updates on all things SDS and Science. 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 or message us on Facebook! This is all for you!

Report of a new variant in DNAJC21 associated with SDS like symptoms

As most of you are aware, over 90% of SDS is caused by bi-allelic mutations in the SBDS gene. We covered that it a recent Snapshots issue. However, there are a few other genes that are implicated in SDS. Except for EFL1, there is no consensus among the science and medical experts whether the syndromes caused by the other genes should be called classic SDS, or rather SDS-like syndromes. DNJC21 is one such gene. It is involved in the pathway of ribosome biogenesis, i.e. the making of active ribosomes. More specifically, it seems to play an important role in building the larger (60S) subunit of the ribosome, ensuring that the "exit tunnel", which is a specific part of it, is properly formed.

Just to give you a rough idea about the complexities involved in ribosome biogenesis - with a large set of proteins working together to make it happen - see this figure from Dr. Warren's article from 2018. No, don't memorize it! Just notice all the different proteins and steps involved in building the 60S large subunit alone.

Back to this week's publication news. Last week, a collaboration between researchers from Turkey, the US, and the UK identified a new mutation in DNAJC21 that seems to lead to an SDS-like syndrome. DNAJC21 has been implicated in SDS before. What is new here is that the new mutation is in a region of the protein that has previous not been known to be important in this pathway / ribosome biogenesis.

You can find the full article, below.

A novel missense mutation outside the DNAJ domain of DNAJC21 is associated with Shwachman-Diamond syndrome.

Alsavaf MB, Verboon JM, Dogan ME, Azizoglu ZB, Okus FZ, Ozcan A, Dundar M, Eken A, Donmez-Altuntas H, Sankaran VG, Unal E. Br J Haematol. 2022 Mar 17. doi: 10.1111/bjh.18112. Online ahead of print. PMID: 35298850

New FDA Guidance on Patient-Focused Drug Development

The U.S. Food and Drug Administration recently released guidance for industry and other stakeholders - Patient-Focused Drug Development: Methods to Identify What Is Important to Patients.

What is a Guidance?

"FDA guidances are documents that explain the agency’s interpretation of, or policy on, a regulatory issue. The FDA prepares guidances primarily for industry, but also for other stakeholders and its own staff, and uses them to address such matters as the design, manufacturing, and testing of regulated products; scientific issues; content and evaluation of applications for product approvals; and inspection and enforcement policies.

Although guidances are not legally binding, they show stakeholders one way to reach their regulatory goal. However, stakeholders are free to use other approaches that satisfy the relevant law and regulations. Recently, FDA published a report on how to improve the processes that make these important documents available." ~ says the FDA.

New Guidance:

Patient-Focused Drug Development: Methods to Identify What Is Important to Patients
Guidance for Industry, Food and Drug Administration Staff, and Other Stakeholders

This is a must-read for all stakeholders - including us - involved in the drug development process. You can download the entire document, here.

Thank you to the FDA and all the stakeholders involved in developing this guidance to improve the process and outcomes for patients in need of treatments.

Beyond just reading it, we are proud to share that we have co-signed a letter containing specific suggestions to improve the guidance -- to be more helpful for the patient advocacy community.

And to make this rather long document more palatable for all of you, several of our friends in the rare disease community came together to read it out loud for you all. Thank you for putting it all together!

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