Regalado Ellen S, Guo Dong-chuan, Prakash Siddharth, Bensend Tracy A, Flynn Kelly, Estrera Anthony, Safi Hazim, Liang David, Hyland James, Child Anne, Arno Gavin, Boileau Catherine, Jondeau Guillaume, Braverman Alan, Moran Rocio, Morisaki Takayuki, Morisaki Hiroko, Pyeritz Reed, Coselli Joseph, LeMaire Scott, Milewicz Dianna M
Departments of Internal Medicine (E.S.R., D.G., S.P., T.A.B., K.F., D.M.M.), Cardiothoracic and Vascular Surgery (A.E., H.S.), University of Texas Health Science Center at Houston; Department of Medicine, Stanford University Medical Center, CA (D.L.); Connective Tissue Gene Tests, Allentown, PA (J.H.); Department of Cardiac and Vascular Sciences, St. George's, University of London, London, United Kingdom (A.C., G.A.); AP-HP, Hôpital Bichat, Centre National de Référence pour le syndrome de Marfan et apparentés, Paris, France (C.B., G.J.), Université Paris 7, Paris, France (C.B., G.J.), AP-HP, Hôpital Bichat, Laboratoire de Génétique moléculaire, Boulogne, France (C.B.), and INSERM, U1148, Paris, France (C.B., G.J.); AP-HP, Hôpital Bichat, Service de Cardiologie, Paris, France (G.J.); Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO (A.B.); Genomic Medicine Institute, Cleveland Clinic, OH (R.M.); Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan (T.M., H.M.); Perelman School of Medicine, University of Pennsylvania, Philadelphia (R.P.); Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (J.C., S.L.); and Texas Heart Institute and Baylor St. Luke's Medical Center, Houston (J.C., S.L.).
Circ Cardiovasc Genet. 2015 Jun;8(3):457-64. doi: 10.1161/CIRCGENETICS.114.000943. Epub 2015 Mar 10.
ACTA2 mutations are the major cause of familial thoracic aortic aneurysms and dissections. We sought to characterize these aortic diseases in a large case series of individuals with ACTA2 mutations.
Aortic disease, management, and outcome associated with the first aortic event (aortic dissection or aneurysm repair) were abstracted from the medical records of 277 individuals with 41 various ACTA2 mutations. Aortic events occurred in 48% of these individuals, with the vast majority presenting with thoracic aortic dissections (88%) associated with 25% mortality. Type A dissections were more common than type B dissections (54% versus 21%), but the median age of onset of type B dissections was significantly younger than type A dissections (27 years versus 36 years). Only 12% of aortic events were repair of ascending aortic aneurysms, which variably involved the aortic root, ascending aorta, and aortic arch. Overall, cumulative risk of an aortic event at age 85 years was 0.76 (95% confidence interval, 0.64-0.86). After adjustment for intrafamilial correlation, sex and race, mutations disrupting p.R179 and p.R258 were associated with significantly increased risk for aortic events, whereas p.R185Q and p.R118Q mutations showed significantly lower risk of aortic events compared with other mutations.
ACTA2 mutations are associated with high risk of presentation with an acute aortic dissection. The lifetime risk for an aortic event is only 76%, suggesting that additional environmental or genetic factors play a role in expression of aortic disease in individuals with ACTA2 mutations.
ACTA2突变是家族性胸主动脉瘤和主动脉夹层的主要原因。我们试图在一个大型的携带ACTA2突变个体病例系列中对这些主动脉疾病进行特征描述。
从277例携带41种不同ACTA2突变的个体的医疗记录中提取与首次主动脉事件（主动脉夹层或动脉瘤修复）相关的主动脉疾病、治疗及转归情况。48%的个体发生了主动脉事件，其中绝大多数表现为胸主动脉夹层（88%），死亡率为25%。A型夹层比B型夹层更常见（54%对21%），但B型夹层的中位发病年龄显著低于A型夹层（27岁对36岁）。仅12%的主动脉事件为升主动脉瘤修复，其不同程度地累及主动脉根部、升主动脉和主动脉弓。总体而言，85岁时主动脉事件的累积风险为0.76（95%置信区间，0.64 - 0.86）。在对家族内相关性、性别和种族进行校正后，破坏p.R179和p.R258的突变与主动脉事件风险显著增加相关，而与其他突变相比，p.R185Q和p.R118Q突变显示主动脉事件风险显著降低。
ACTA2突变与急性主动脉夹层的高风险相关。主动脉事件的终生风险仅为76%，这表明其他环境或遗传因素在携带ACTA2突变个体的主动脉疾病表达中起作用。
