Aneurysms of the aorta can involve either the aorta in the thoracic cavity (thoracic aortic aneurysms or TAA) or in the abdominal cavity (abdominal aortic aneurysms). Initially we sought to determine the familial aggregation of TAAs. These studies demonstrated that first-degree relatives of patients with thoracic aortic aneurysms or dissections were at increased risk for both thoracic aortic aneurysms and sudden death. The familial aggregation of thoracic aortic aneurysms suggests a genetic predisposition that causes the formation of aneurysms in some families. Thoracic aortic aneurysms can result from known genetic syndrome like the Marfan syndrome, an autosomal dominant condition that results from mutations in the FBN1 gene. In addition, thoracic aortic aneurysms can be inherited in an autosomal dominant manner without the other clinical manifestations of the Marfan syndrome. Our study has shown that patients with thoracic aortic aneurysms and dissections who do not have the Marfan syndrome can have mutations in the FBN1 gene. By obtaining family histories from patients with thoracic aortic aneurysms, we have identified 10 families with autosomal dominant inheritance of thoracic aortic aneurysms/dissections. In the minority of these families (2) the phenotype is linked to FBN1 (using polymorphic markers within FBN1). In the remainder of families the phenotype is either not linked to FBN1 or the family is not informative using the currently available markers. These results indicate that although FBN1 mutations may account for some familial aneurysms, there are other gene or genes involved. Through these studies we hope to be able to identify individuals at risk for thoracic aortic aneurysms and dissections and prevent untimely and premature deaths. These studies should also provide information on the proteins that give structural integrity to the thoracic aorta.
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