Connective Issues Winter 2024

It doesn’t confirm or rule out a genetic condition. Over time, as more research is done, the classification of a VUS might change. It’s important not to use a VUS for making medical decisions, as its significance is not clear. Testing of family members for a VUS is generally not recommended and wouldn’t be helpful outside of specific situations where your family could help scientists learn more about the VUS. The lab or genetics professional involved would help to coordinate this, if applicable. Q: Can the interpretation of genetic test results change over time? A: Yes, as genetic research advances, interpretations of FOUNDATION HOSTS Marfan-Focused Symposium The Foundation sponsored a guest symposium focused on aortic disease in Marfan syndrome and related conditions at the American Society for Matrix Biology meeting in October. The meeting hosted 550 students, trainees, investigators, and educators from around the world who work on cutting-edge basic, clinical, and translational research related to biology of cells and tissues, as well as molecular and cellular alterations that drive disease processes. Dr. Jo Grima, Chief ScienceO ffi cer at the Foundation, and Dr. Lynn Sakai, Adjunct Research Professor at Oregon Health & Science University and member of the Foundation’s Professional Advisory Board, chaired the Marfan symposium. “A major goal of the ASMB meeting is to get a better understanding of matrix disorders, and therefore, provides an opportunity to bring together leaders in the field to discuss conditions like Marfan syndrome,” said Dr. Sakai. “The opportunity to learn about and discuss these important studies is crucial to finding treatments and improving the lives of those with Marfan, Loeys Dietz, VEDS, and related conditions.” Several speakers (see sidebar) were invited to present their work. Dr. Chris Schoenherr discussed a new approach for screening candidate genes that may modify severe aortic disease in Marfan mice and showed positive results for at least one gene. Two other studies were based on recent trends investigating di ff erences in the progression and outcomes between males and females a ff ected with Marfan syndrome. Since 2010, many clinical studies in humans have shown that men have a higher risk for aortic aneurysm, dissections, and surgery. Several other studies have documented this increased risk in males using di ff erent Marfan mouse strains. At this meeting, studies presented by Dr. Dieter Reinhardt and Dr. Sarah Parker attributed these sex di ff erences to possible hormonal protective

test results may evolve. This is especially true for VUS, where new information can change how these variants are viewed. It’s essential to keep up-to-date and talk with your healthcare provider about any new information. Q: What are the next steps after receiving genetic test results? A: Discuss your results with your doctor or genetic counselor. They can help you understand what the results mean in relation to your health and family history, and suggest the next steps. This might include specific medical care, lifestyle changes, or more genetic testing for you or your family. Genetic testing is just one part of managing and understanding your health.

e ff ects in females. One study suggested that increased estrogen levels could account for these di ff erences since male Marfan mice treated with estradiol showed improvements in a few aortic markers and reduced aortic root sizes. Although treatment of males with estradiol did not return them to normal. These studies indicate that additional work investigating the role of hormones may provide some valuable insights for future treatments. Clinical studies of women with Marfan syndrome and related conditions who are on estrogen therapies may be an important next step. • Targeting Aortic Aneurysm in Marfan Syndrome Mice Chris Schoenherr, PhD, Regeneron Pharmaceuticals • Sex-Specific Pathologies in the Aorta and Fat Tissue of Marfan Mice – Dieter Reinhardt, PhD, McGill University • Leveraging Molecular Patterns of Resiliency in Females to Understand Drivers of Aneurysm Severity in Marfan Syndrome – Sarah Parker, PhD, Cedars-Sinai Medical Center • Fibulin-4 and Fibulin-5 Serve Distinct, Non-Overlapping Functions in Elastic Fiber Assembly and Cardiovascular Physiology – Carmen Halabi, MD, PhD, Washington University • O-Glucose Modification of Fibrillin Epidermal Growth Factor Repeats is Essential for Mouse Lung Development Sanjiv Neupane, PhD, Stony Brook University Presenters: Aortic Disease in Marfan Syndrome and Related Conditions

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Winter 2024