Mutation of ACTA2 gene as an important cause of familial and nonfamilial nonsyndromatic thoracic aortic aneurysm and/or dissection (TAAD).
Approximately 20% of aortic aneurysm and/or dissection (AAD) cases result from inherited disorders, including several systemic and syndromatic connective-tissue disorders, such as Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome, which are caused by mutations in the FBN1, COL3A1, and TGFBR1 and TGFBR2 genes, respectively. Nonsyndromatic AAD also has a familial background, and mutations of the ACTA2 gene were recently shown to cause familial AAD. In the present study, we conducted sequence analyses of the ACTA2 gene in 14 unrelated Japanese patients with familial thoracic AAD (TAAD), and in 26 with sporadic and young-onset TAAD. 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. Some of the clinical features of these patients were the same as previously reported, whereas others were different. These findings confirm that ACTA2 mutations are important in familial TAAD, while the first sporadic and young-onset TAAD case with an ACTA2 mutation was also identified.
Morisaki
Hiroko
H
Department of Bioscience, National Cardiovascular Center Research Institute, Osaka, Japan.
Akutsu
Koichi
K
Ogino
Hitoshi
H
Kondo
Norihiro
N
Yamanaka
Itaru
I
Tsutsumi
Yoshiaki
Y
Yoshimuta
Tsuyoshi
T
Okajima
Toshiya
T
Matsuda
Hitoshi
H
Minatoya
Kenji
K
Sasaki
Hiroaki
H
Tanaka
Hiroshi
H
Ishibashi-Ueda
Hatsue
H
Morisaki
Takayuki
T
D000199:Actins / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics*; D001019:Aortic Rupture / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
C541116:ACTA2 protein, human; D000199:Actins