Familial thoracic aortic aneurysms and dissections: Three families with early‐onset ascending and descending aortic dissections in women

• Published in: American journal of medical genetics. Part A 2006-06, Vol.140A (11), p.1196-1202
• Main Authors: Tran‐Fadulu, Van, Chen, Julia H., Lemuth, Danielle, Neichoy, Bo T., Yuan, Jiuhong, Gomes, Nathan, Sparks, Elizabeth, Kramer, Larry A., Guo, Dongchuan, Pannu, Hariyadarshi, Braverman, Alan C., Shete, Sanjay, Milewicz, Dianna M.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; aneurysm; Aneurysm, Dissecting - genetics; Aneurysm, Dissecting - pathology; aorta; Aorta - pathology; Aorta, Thoracic - pathology; Aortic Aneurysm, Thoracic - genetics; Aortic Aneurysm, Thoracic - pathology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Diseases of the aorta; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; dissection; DNA Mutational Analysis; familial thoracic aortic aneurysms and dissections; Family Health; Female; Gene Frequency; Genetic Linkage; Genetic Predisposition to Disease - genetics; genetics; Genotype; Humans; Lod Score; Male; Medical sciences; Microsatellite Repeats - genetics; Pedigree; Sex Factors; Time Factors
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.31236

Ascending thoracic aortic aneurysms leading to type A dissections can be inherited in an autosomal dominant manner with variable age of onset and decreased penetrance, primarily in women. Three families are described with autosomal dominant inheritance of either ascending aortic aneurysms leading to type A dissections or type B dissections, and a young age of onset of aortic dissections in both men and women. Pedigree analysis suggests that a de novo mutation is responsible for the disease in one family. The discordant age of onset of aortic disease in a monozygotic twin pair in a different family indicates that environmental or stochastic factors may influence the variable expression of disease. Genetic analysis of one family excluded linkage to known loci for TAAD (TAAD1, TAAD2, FAA1, or FBN1) and sequence analysis failed to identify mutations in TGFBR2, the gene encoding transforming growth factor beta receptor type II. Thus, a novel unidentified loci may be responsible for the phenotype in these three families. © 2006 Wiley‐Liss, Inc.