title: Clinical, pathological, and genetic analysis of a Korean family with thoracic aortic aneurysms and dissections carrying a novel Asp26Tyr mutation.
abstract: Non-syndromic familial thoracic aortic aneurysms and dissections (TAADs), inherited in an autosomal dominant manner in up to 19% of patients, are genetically heterogeneous. The ACTA2 gene, which encodes the vascular smooth muscle cell (SMC)-specific isoform of alpha-actin, is known to cause TAADs and occlusive vascular diseases, including coronary artery disease and premature ischemic stroke. We have investigated a Korean family with DeBakey type I aortic dissection related to pregnancy and a strong family history of TAADs. All affected family members underwent surgical repair of the ascending aorta. Other clinical features of familial TAAD, including inguinal hernias, iris flocculi, and livedo reticularis, were not observed. Histologic studies of aortic tissues showed medial degeneration and SMC hyperplasia in the aorta, consistent with previous observations. Molecular analyses of the ACTA2 gene showed a novel heterozygous missense mutation (c.76G>T; p.Asp26Tyr). Further analysis of a female patient and members of her family revealed that two affected sisters and her asymptomatic son had the same mutation. The novel Asp26Tyr mutation resides in SM alpha-actin subdomain 1 and is linked to TAAD with hypertrophy and disarray of SMCs and severe migraine, but not to livedo reticularis or iris flocculi. This study expands the spectrum of mutations of the ACTA2 gene by identifying a novel missense mutation. This is the first report of a pathologically- and genetically-confirmed family with TAAD in Korea.
authors.affiliation: Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Korea 135-710.
authors.forename: Eun-Hyung
authors.initials: EH
authors.lastname: Yoo
authors.forename: Seung Hyuk
authors.initials: SH
authors.lastname: Choi
authors.forename: Shin Yi
authors.initials: SY
authors.lastname: Jang
authors.forename: Yeon-Lim
authors.initials: YL
authors.lastname: Suh
authors.forename: Inchul
authors.initials: I
authors.lastname: Lee
authors.forename: Jae-Kwan
authors.initials: JK
authors.lastname: Song
authors.forename: Yeon Hyeon
authors.initials: YH
authors.lastname: Choe
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Duk-Kyung
authors.initials: DK
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000235:genetics*; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000784:Aortic Dissection / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D017545:Aortic Aneurysm, Thoracic / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D015992:Body Mass Index; D017931:DNA Primers / Q000737:chemistry / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007723:Korea; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D011379:Prognosis; D011859:Radiography; D017386:Sequence Homology, Amino Acid; D055815:Young Adult
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D017931:DNA Primers