title: Familial thoracic aortic aneurysms and dissections: three families with early-onset ascending and descending aortic dissections in women.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Division of Medical Genetics, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.
authors.forename: Van
authors.initials: V
authors.lastname: Tran-Fadulu
authors.forename: Julia H
authors.initials: JH
authors.lastname: Chen
authors.forename: Danielle
authors.initials: D
authors.lastname: Lemuth
authors.forename: Bo T
authors.initials: BT
authors.lastname: Neichoy
authors.forename: Jiuhong
authors.initials: J
authors.lastname: Yuan
authors.forename: Nathan
authors.initials: N
authors.lastname: Gomes
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sparks
authors.forename: Larry A
authors.initials: LA
authors.lastname: Kramer
authors.forename: Dongchuan
authors.initials: D
authors.lastname: Guo
authors.forename: Hariyadarshi
authors.initials: H
authors.lastname: Pannu
authors.forename: Alan C
authors.initials: AC
authors.lastname: Braverman
authors.forename: Sanjay
authors.initials: S
authors.lastname: Shete
authors.forename: Dianna M
authors.initials: DM
authors.lastname: Milewicz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000784:Aortic Dissection / Q000235:genetics* / Q000473:pathology; D001011:Aorta / Q000473:pathology; D001013:Aorta, Thoracic / Q000473:pathology; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D012737:Sex Factors; D013997:Time Factors