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SDS & Science Snapshots (2024-05-11)

In this issue: SDS identified as a common cause of inherited neutropenia in the Israeli Inherited Bone Marrow Failure Registry!

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 genetics@SDSAlliance.org or message us on Facebook! This is all for you!



The Genetic Landscape of Inherited Neutropenia in the Israeli Inherited Bone Marrow Failure Registry


In a study recently published in April, researchers investigated the genetic landscape of inherited neutropenia within the Israeli population. As many individuals in the Shwachman-Diamond Syndrome (SDS) community are familiar, neutropenia is characterized by abnormally low levels of neutrophils (a type of white blood cell which plays an important role in the immune system) and can leave individuals vulnerable to recurrent infections and other health complications. This new study, conducted with participants from the Israeli Inherited Bone Marrow Failure Registry, shed light on the genetic cause of inherited neutropenia in Israel, offering hope for improved diagnosis and management strategies.


Out of the 65 individuals with inherited neutropenia enrolled in the Israeli Inherited Bone Marrow Failure Registry, 74% received a genetic diagnosis. As pictured below, the most common forms of inherited neutropenia identified were ELANE neutropenia and G6PC3-severe congenital neutropenia. Interestingly, diagnoses of SDS and SDS-like syndromes were the third and fourth most common cause of inherited neutropenia in the Israeli Inherited Bone Marrow Failure Syndrome study with more than 25% of individuals having variants identified in the SBDS and SRP54 genes.


Among those with positive genetic testing, 15% had two mutations (or variants) detected in the SBDS gene. These individuals, primarily of Jewish or Arab Muslim descent, presented with a spectrum of common SDS symptoms, including pancreatic insufficiency, severe infections, and skeletal abnormalities.


Interestingly, around 12% of individuals with positive genetic testing had one mutation identified in the SRP54 gene, reported to cause an SDS-like syndrome. These individuals (even individuals within the same family) displayed a range of symptoms, including a few with mild, resolving exocrine pancreatic insufficiency and failure to thrive, reminiscent of SDS caused by SBDS mutations. When we reached out to Dr. Steinberg-Shemer, she highlighted that patients with SRP54 in Israel actually had isolated neutropenia with no significant pancreatic insufficiency.


For more information about the symptoms and genetic cause of SDS, you can watch the video below.



Importantly, the study reported that while none of the participants with SDS or SDS-like syndromes had been diagnosed with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), one individual successfully underwent a bone marrow transplant due to bone marrow failure. However, the authors of this study emphasized the importance of participating in regular bone marrow surveillance for those with SDS diagnoses.


These findings show the importance of participating in genetic testing for individuals with chronic neutropenia and frequent infections, especially for those at a young age. By identifying the genetic cause behind inherited neutropenia conditions, healthcare teams can tailor disease management strategies such as regular bone marrow surveillance for those with SDS. As we were reminded in last week’s SDS & Science Snapshot, understanding the genetic landscape of SDS and SDS-like syndromes in diverse populations, like in this Israeli cohort, is crucial for advocating for improved treatments and outcomes for individuals with SDS and SDS-like syndromes worldwide.


 

For more information regarding the clinical presentation of SDS and flyers about SDS to share with your care team, you can visit our “What is SDS?” page.


Disclaimer: The information contained in this blog post is an overview of published research and is not intended to be medical advice. If you are concerned you, or a loved one, has SDS, please contact your healthcare team.





Yeshareem L, Yacobovich J, Lebel A, Noy-Lotan S, Dgany O, Krasnov T, Berger Pinto G, Oniashvili N, Mardoukh J, Bielorai B, Laor R, Mandel-Shorer N, Ben Barak A, Levin C, Asleh M, Miskin H, Revel-Vilk S, Levin D, Benish M, Zuckerman T, Wolach O, Pazgal I, Brik Simon D, Gilad O, Yanir AD, Goldberg TA, Izraeli S, Tamary H, Steinberg-Shemer O.


Genetic backgrounds and clinical characteristics of congenital neutropenias in Israel. Eur J Haematol. 2024 Apr 11. doi: 10.1111/ejh.14197. Epub ahead of print. PMID: 38600884.



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