Clinical, pathological, and genetic analysis of a Korean family with thoracic aortic aneurysms and dissections carrying a novel Asp26Tyr mutation.
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.
Yoo
Eun-Hyung
EH
Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Korea 135-710.
Choi
Seung Hyuk
SH
Jang
Shin Yi
SY
Suh
Yeon-Lim
YL
Lee
Inchul
I
Song
Jae-Kwan
JK
Choe
Yeon Hyeon
YH
Kim
Jong-Won
JW
Ki
Chang-Seok
CS
Kim
Duk-Kyung
DK
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
C541116:ACTA2 protein, human; D000199:Actins; D017931:DNA Primers