Genetic basis of thoracic aortic aneurysms and aortic dissections.
Ascending thoracic aortic aneurysms leading to type A dissections (TAAD) can occur in association with a genetic syndrome, such as Marfan syndrome (MFS), or as an autosomal dominant disorder in the absence of syndromic features, termed familial TAAD. Familial TAAD demonstrates genetic heterogeneity, and linkage studies have identified three TAAD loci at 5q13-14 (TAAD1), 11q23 (FAA1), and 3p24-25 (TAAD2). The underlying genetic heterogeneity of TAAD is reflected in the phenotypic variation associated with familial TAAD with respect to age of onset, progression, penetrance, and association with additional cardiac and vascular features. Recently, mutations in the TGFBR2 gene have been identified as the cause of disease linked to the TAAD2 locus, supporting the hypothesis that dysregulation of TGFbeta signaling is a mechanism leading to aneurysms and dissections. The recent identification of the TGFbeta pathway as a key target in the molecular pathogenesis of TAAD has opened new avenues for future genetic and therapeutic research.
Pannu
Hariyadarshi
H
Division of Medical Genetics, Department of Internal Medicine, University of Texas Medical School, Houston, USA.
Tran-Fadulu
Van
V
Milewicz
Dianna M
DM
D001014:Aortic Aneurysm / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D000071837:Fibrillins; D005799:Genes, Dominant / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D053779:Latent TGF-beta Binding Proteins; D008840:Microfilament Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D019683:Penetrance; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000071837:Fibrillins; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D008840:Microfilament Proteins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II