Abstract
Background-Thoracic aortic aneurysms leading to acute aortic dissections are the major diseases that affect the thoracic aorta. Approximately 20% of patients with thoracic aortic aneurysms and dissections (TAAD) have a family history of TAAD, and these patients present younger with more rapidly enlarging aneurysms than patients without a family history of aortic disease. Methods and Results-A large family with multiple members with TAAD inherited in an autosomal-dominant manner was identified. The ascending aortic aneurysms were associated with slow enlargement, a low risk of dissection, and decreased penetrance in women. Genome-wide linkage analysis was performed, and a novel locus on chromosome 12 was identified for the mutant gene causing disease in this family. Of the 12 male members who carry the disease-linked microsatellite haplotype, 9 had ascending aortic aneurysms with an average diameter of 4.7 cm at an average age of 52.4 years (range, 32 to 76 years) at the time of diagnosis; only 1 individual had progressed to acute aortic dissection, and no other members with aortic dissections were identified. Women harboring the disease-linked haplotype did not have thoracic aortic disease, including 1 aged 84 years. Sequencing of 9 genes within the critical interval at the chromosome 12 locus did not identify the mutant gene. Conclusions-Mapping a locus for ascending thoracic aortic aneurysms associated with a low risk of aortic dissection supports our hypothesis that genes leading to familial disease can be associated with less-aggressive thoracic aortic disease.
Original language | English (US) |
---|---|
Pages (from-to) | 36-42 |
Number of pages | 7 |
Journal | Circulation: Cardiovascular Genetics |
Volume | 4 |
Issue number | 1 |
DOIs | |
State | Published - Feb 2011 |
Keywords
- Aneurysm
- Aorta
- Dissection genes
- Genome-wide association analysis
- Mapping
- Risk
ASJC Scopus subject areas
- Genetics
- Cardiology and Cardiovascular Medicine
- Genetics(clinical)
MD Anderson CCSG core facilities
- Biospecimen Extraction Facility