2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Historical prospective study of the link between JAK2-V617F and thoracic aortic aneurysm

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A low-level mosaicism for JAK2-V617F is commonly found in the general population, particularly among individuals over the age of 70. This is often seen in the presence of Clonal Hematopoiesis of Indeterminate Potential. The JAK2-V617F variant plays a significant role in the development of various myeloproliferative neoplasms and is also associated with venous thromboses and vascular complications such as coronary artery disease. Recent research has shown that it may also be linked to thoracic and abdominal aortic aneurysms. Thoracic aortic aneurysms are known to be dangerous and typically remain asymptomatic until they rupture. The incidence and prevalence of thoracic aortic aneurysms are relatively low, with a mean age of occurrence at 65 years.<br /><br />This study aimed to investigate the association between JAK2-V617F and thoracic aortic aneurysms. The researchers utilized an in-house exome database containing clinical-grade exomes from over 4000 patients. Among them, 492 patients were referred for genetic evaluation of thoracic aortic aneurysms or connective tissue disorders. Clinical information from carriers of the JAK2-V617F variant was reviewed, revealing a surprisingly high occurrence of thoracic aortic aneurysms in this population compared to the overall database. However, further investigation is needed, including larger longitudinal studies among JAK2-V617F carriers, to properly assess the association between the variant and thoracic aortic aneurysms.<br /><br />The study identified six patients with the JAK2-V617F variant in the internal database, ranging in age from 50 to 87 years. Four of these patients developed myeloproliferative neoplasms, and two presented with abnormal complete blood count findings suggestive of anemia. Additionally, three of the six JAK2-V617F carriers had thoracic aortic aneurysms. The research utilized a genotype-first approach to explore the possible link between the JAK2-V617F variant and thoracic aortic aneurysms.<br /><br />In summary, this study suggests a potential association between the JAK2-V617F variant and thoracic aortic aneurysms. Further research is needed to confirm this link and to better understand the relationship between the variant and cardiovascular conditions.

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Presenting Author - Deqiong Ma, MD, PhD, FACMG; Co-Author - Andreea Popa, MD, PhD; Co-Author - Daniel Dykas, MBA; Co-Author - Bulat Ziganshin, MD; Co-Author - Mohammad Zafar, MBBS; Co-Author - John Elefteriades, MD; Co-Author - Hui Zhang, MD, PhD; Co-Author - Allen E. Bale, MD;

Meta Tag

Cardiac/circulatory disorders

Exome sequencing

Co-Author Andreea Popa, MD, PhD

Co-Author Daniel Dykas, MBA

Co-Author Bulat Ziganshin, MD

Co-Author Mohammad Zafar, MBBS

Co-Author John Elefteriades, MD

Co-Author Hui Zhang, MD, PhD

Co-Author Allen E. Bale, MD

Presenting Author Deqiong Ma, MD, PhD, FACMG

Keywords

low-level mosaicism

JAK2-V617F

general population

Clonal Hematopoiesis of Indeterminate Potential

myeloproliferative neoplasms

venous thromboses

vascular complications

coronary artery disease

thoracic aortic aneurysms

genetic evaluation