title: Mutation of ACTA2 gene as an important cause of familial and nonfamilial nonsyndromatic thoracic aortic aneurysm and/or dissection (TAAD).
abstract: 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.
authors.affiliation: Department of Bioscience, National Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Morisaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Akutsu
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ogino
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kondo
authors.forename: Itaru
authors.initials: I
authors.lastname: Yamanaka
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshimuta
authors.forename: Toshiya
authors.initials: T
authors.lastname: Okajima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Matsuda
authors.forename: Kenji
authors.initials: K
authors.lastname: Minatoya
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Hatsue
authors.initials: H
authors.lastname: Ishibashi-Ueda
authors.forename: Takayuki
authors.initials: T
authors.lastname: Morisaki
mesh_terms: 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
chemical_list: C541116:ACTA2 protein, human; D000199:Actins