A SMAD3 mutation has been linked to aneurysm-osteoarthritis syndrome and has been identified as a cause of familial thoracic aortic aneurysm and dissection.
Familial aortic aneurysm (FAA) has been described in such conditions as the Marfan and Ehlers-Danlos type IV syndromes, due to defects in the fibrillin-1 and type III procollagen genes, respectively.
Two novel ACTA2 mutations (N117I and L348R) were identified in each familial TAAD proband separately, and an additional novel ACTA2 mutation (Y168N) was identified in one patient with sporadic TAADs.
Our results identified three mutations of ACTA2, two novel [p.G152_T205del (c.616+1G>T), p.R212Q] and one reported (p.R149C), in the 14 patients with familial TAAD, and a novel mutation (p.Y145C) of ACTA2 in the 26 sporadic and young-onset TAAD patients, each of which are considered to be causative for TAAD.
These data, along with the previously reported MYH11 mutations causing familial TAAD, indicate the importance of SMC contraction in maintaining the structural integrity of the ascending aorta.
To describe the clinical findings and natural history in 22 carriers of an R460H mutation in the transforming growth factor beta receptor 2 gene (TGFbetaR2) from a five-generation kindred ascertained by familial aortic dissection.
Mutations in myosin heavy chain (MYH11), a smooth muscle cell-specific contractile protein, have been identified in familial TAAD associated with patent ductus arteriosus (PDA) linked to 16p12.2-12.13.
In previous studies, investigators identified genetic markers shared by a subset of families who were ascertained to have the disease, which clustered into 2 chromosomal regions: 5q13-q15 (TAAD1) and 11q23.2-q24 (familial aortic aneurysm [FAA1]).
Genome-wide linkage analysis identified a 2.3-cM FAA locus (FAA1) on chromosome 11q23.3-q24 with a maximum multipoint logarithm of the odds score of 4.4.