Familial thoracic aortic aneurysms and dissections: three families with early-onset ascending and descending aortic dissections in women.
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.
Tran-Fadulu
Van
V
Department of Internal Medicine, Division of Medical Genetics, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.
Chen
Julia H
JH
Lemuth
Danielle
D
Neichoy
Bo T
BT
Yuan
Jiuhong
J
Gomes
Nathan
N
Sparks
Elizabeth
E
Kramer
Larry A
LA
Guo
Dongchuan
D
Pannu
Hariyadarshi
H
Braverman
Alan C
AC
Shete
Sanjay
S
Milewicz
Dianna M
DM
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