| 摘要: |
| 摘要
目的：研究主动脉病变相关基因在二叶式主动脉瓣（Bicuspid aortic valve，BAV）相关性主动脉病变中的作用。
方法：纳入2014年4月至2016年6月于北京安贞医院行Bentall手术并检测到主动脉病变相关基因的突变的BAV患者8例。并排除具有主动脉病变家族史的BAV患者。收集患者外周血并针对已报道的主动脉疾病相关基因进行筛查。将基因突变的结果在多个数据库中进行检索，排除其为单核苷酸多肽性（SNPs）。通过多个突变评价软件对变异进行致病性预测。记录患者的一般临床参数及实验室检查结果，利用超声心动图评估其BAV分型、瓣膜功能及升主动脉内径等指标。
结果：8例检测到主动脉病变相关基因的突变的BAV患者男性7例，女性1例，平均年龄50.25岁（28-71岁）。8例患者均。其中4例患者FBN1基因突变（c.2926C>Tp.Arg976Cys，c.2374T>Cp.Cys792Arg，c.2639G>Ap.Gly880Asp，c.6700G>Ap.Val2234Met），2例COL3A1基因突变（c.2190A>Tp.GLU730Asp，c.2181G>Ap.Met727Ile），1例MYLK基因突变（c.1414C>Tp.Leu472Phe），1例TGFBR1基因突变（c.134A >Gp.Asn45Ser）。8例患者中1例FBN1基因突变患者为Sievers 0型，余7例均为Sievers I型BAV，其中RL型6例，RN型1例。8例患者中5例患者主动脉最宽处位于升主动脉管部，3例位于主动脉窦部。2例以主动脉瓣狭窄表现为主，5例以主动脉瓣关闭不全表现为主，1例主动脉瓣狭窄与关闭不全程度相当。3例FBN1基因突变（c.2926C>Tp.Arg976Cys，c.2374T>Cp.Cys792Arg，c.2639G>Ap.Gly880Asp）经3个突变评价软件预测均为可能致病性突变，该3例患者胸主动脉最宽处内径显著高于其它基因突变患者。
结论：主动脉病变相关基因可能参与BAV相关性主动脉病变的发生发展。基因变异相关的解剖结构异常所引起的血流动力学改变可能最终导致了BAV患者不同类型的主动脉病变。 |
| 关键词: 二叶式主动脉瓣 基因 二叶式主动脉瓣相关性主动脉病变 超声心动图 |
| DOI： |
| 投稿时间：2019-08-22修订日期：2019-08-22 |
| 基金项目: |
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| Medical Imaging and Genetics Study of Aortic Disease Related Gene Mutations in Bicuspid Aortic Valve Patients |
| quyichen,liyijia,yangya |
| (Anzhen Hospital,Capital Medical University) |
| Abstract: |
| Abstract
Objective: To investigate the roles of aortic disease related genes in bicuspid aortopathy.
Methods: 8 BAV patients without family history of aortic disesae who underwent Bentall surgery and found variants of reported aortic disease related genes in Anzhen hospital of Capital Medical University from April 2014 to June 2016 were included. General clinical parameters and laboratory examination results of the patients were recorded. Echocardiography was used to evaluate the BAV classification, valve function, ascending aortic diameter and other indicators. Genetic variations were searched in three major database to exclude the SNPs, and predicted by 3 online software: PROVEAN, Mutation Taster and PolyPhen-2.
Results: We included 8 patients with average age of 50.25 years (28-71 years), and only one of which was female. All cases were identified with one target gene mutated. There were four cases of FBN1 gene mutation (c.2926C> Tp.arg976cys, c.2374T>Cp.Cys792Arg, c.2639G>Ap.Gly880Asp, c.6700G>ApVal2234Met), two cases of COL3A1 gene mutation (c.2190A>Tp.GLU730Asp，c.2181G>Ap.Met727Ile), one cases of MYLK gene mutation (c.1414C>Tp.Leu472Phe), and one case of TGFBR1 gene mutation (c.134A >Gp.Asn45Ser). Except for one case with FBN1 gene mutation had BAV of Sievers type 0, the remaining 7 were all Sievers type I, including 6 cases of RL fusion pattern and 1 case with RN fusion pattern. The widest part of the aorta was located in the tubular ascending aorta in 5 cases and the aorta sinus in 3 cases. Two cases were predominant aortic stenosis（AS）, while 5 were predominant aortic regurgitation（AR）, and one was comparable to aortic stenosis and regurgitation. The maximum diameter of thoracic aorta of 3 patients with FBN1 gene mutations (c.2926C> tp.arg976cys, c.2374T>Cp.Cys792Arg，c.2639G>Ap.Gly880Asp), which predicted by all 3 software to be disease causing mutations, were significantly higher than that of the patients with other gene mutations.
Conclusion: Aortic disease related genes may be involved in the development of BAV related aortic disease. Hemodynamic changes associated with anatomic abnormalities resulted from genetic variations may ultimately lead to different BAV aortopathy phenotype. |
| Key words: Bicuspid aortic valve (BAV) gene bicuspid aortopathy echocardiography |
