Genetic Variants Linked to Multiple Arterial Aneurysms in Patients
Overview
This study identified 24 genetic variants in 23 genes associated with vascular diseases in nine male patients with multiple arterial aneurysms. Variants included missense, frameshift, and nonsense mutations linked to conditions such as Loeys-Dietz syndrome, Ehlers-Danlos syndrome, and clonal hematopoiesis of indeterminate potential.
Background
Arterial aneurysms involve vessel dilation exceeding 150% of the normal diameter, often caused by chronic inflammation leading to vessel wall degradation and risk of rupture. The abdominal aortic aneurysm is the most common type, with significant mortality worldwide. Genetic factors contribute to aneurysm formation, especially in thoracic aortic aneurysm and dissection, and may influence disease onset and clinical outcomes in patients with multiple aneurysms. Understanding genetic variants in these patients can guide risk assessment and management.
Data Highlights
Patient
Aneurysm Count
Age at Diagnosis (years)
Genetic Variant
Associated Disorder
1
8
40
SMAD3 (heterozygous)
Loeys-Dietz syndrome 3
2
5
58
TNXB (heterozygous)
Ehlers-Danlos syndrome (Classic-Like)
3
6
78
TET2 (frameshift & nonsense), PPM1D
Clonal hematopoiesis of indeterminate potential
Key Findings
Nine male patients with multiple arterial aneurysms (4-8 aneurysms each) were analyzed using whole exome sequencing.
A total of 24 variants in 23 genes associated with vascular diseases were identified, including 14 missense, 7 frameshift, and 3 nonsense variants.
Variants were linked to diverse vascular disorders such as abdominal and thoracic aortic aneurysms, Ehlers-Danlos syndrome, coronary artery disease, and cardiovascular disease.
One patient with 8 aneurysms carried a heterozygous SMAD3 variant associated with Loeys-Dietz syndrome 3, diagnosed at age 40.
Another patient with 5 aneurysms had a heterozygous TNXB variant linked to Classic-Like Ehlers-Danlos syndrome, diagnosed at age 58.
A third patient with 6 aneurysms harbored two TET2 variants and one PPM1D variant related to clonal hematopoiesis, diagnosed at age 78.
Clinical Implications
Genetic testing should be considered in patients presenting with multiple arterial aneurysms, especially those with early onset or systemic involvement, to identify underlying hereditary conditions. Detection of pathogenic variants can inform personalized surveillance and management strategies, including genetic counseling for patients and families. Awareness of diverse genetic contributors beyond classical connective tissue disorders is important for comprehensive care.
Conclusion
This study highlights the presence of diverse genetic variants in patients with multiple arterial aneurysms, underscoring the role of genetics in multifocal aneurysm formation. Incorporating genetic analysis into clinical practice may enhance risk stratification and therapeutic decision-making.
References
Author/Source/Year -- Genetic Factors Associated with Multiple Arterial Aneurysms in Patients
