本文選題：主動(dòng)脈夾層　切入點(diǎn)：腹主動(dòng)脈瘤　出處：《南京大學(xué)》2017年碩士論文

【摘要】：研究背景:主動(dòng)脈夾層(thoracic aorta dissection,TAD)和腹主動(dòng)脈瘤(abdominal aorta aneurysm,AAA)都是嚴(yán)重威脅人類健康的疾病。這兩種疾病一般起病隱匿,一旦發(fā)生主動(dòng)脈破裂,預(yù)后極其不良。TAD是一種單基因遺傳病。目前研究已證實(shí)可導(dǎo)致TAD疾病有數(shù)十種基因。多種綜合征疾病可表現(xiàn)為T(mén)AD,比如馬凡綜合征(Marfan syndrome)、Loeys-Dietz syndrome(LDS)、Ehlers-Danlos syndrome(血管型)、Turner syndrome等。這些疾病常常在患者成年前發(fā)病,致死率非常高。但由于臨床表型在不同疾病或同一種疾病中不盡相同,也有少部分綜合征患者臨床癥狀輕微,在成年甚至中年才有TAD表現(xiàn),這些因素都增加了臨床醫(yī)生診斷TAD病因的難度。AAA一般發(fā)病年齡超過(guò)60歲,是一種多基因共同致病、受環(huán)境等外界因素影響的疾病。高齡的AAA患者的病因主要為高血壓、吸煙和動(dòng)脈粥樣硬化形成。但年輕的AAA患者,尤其是有家族史的患者,臨床醫(yī)生往往無(wú)法提供病因診斷、生活指導(dǎo)、生育及遺傳咨詢。在過(guò)去的30多年中,學(xué)者一直在研究AAA的致病基因,但成果不盡人意。有些成果甚至互相矛盾。像TAD一樣,AAA也可以由多種綜合征疾病導(dǎo)致,病因診斷困難。全外顯子組測(cè)序(Whole Exome Sequencing,WES)能夠?qū)蚪M全部外顯子進(jìn)行測(cè)序分析,可以高效地發(fā)現(xiàn)已知致病基因的突變甚至可以發(fā)現(xiàn)新的致病基因。目的:鑒定主動(dòng)脈夾層和腹主動(dòng)脈瘤的致病基因。方法:運(yùn)用WES技術(shù)對(duì)3例Stanford B型主動(dòng)脈夾層患者、1例腹主動(dòng)脈瘤患者進(jìn)行測(cè)序分析。結(jié)果:我們發(fā)現(xiàn)2例Stanford B型主動(dòng)脈夾層存在FBN1基因突變分別為c.G6953A(p.C2318Y)和 c.4786T(p.RJ596X);發(fā)現(xiàn) 1 例 Stanford B 型主動(dòng)脈夾層存在PKD2基因突變c.C1774T(p.R592X);首次鑒定了 TGFBR1(rs113605875,exon9,c.G1460A,p.R487Q)基因?yàn)?AAA 的致病基因;首次報(bào)道了由TGFBR1基因突變導(dǎo)致的AAA家系。結(jié)論:與高齡散發(fā)的主動(dòng)脈夾層和腹主動(dòng)脈瘤不同,我們建議對(duì)早發(fā)的患者進(jìn)行病因研究,必要時(shí)可運(yùn)用WES技術(shù)以明確病因。致病基因的鑒定不僅有助于臨床診斷,而且有助于臨床決策、生活方式指導(dǎo)、藥物治療、定期篩查、生育及遺傳咨詢。
[Abstract]:Background: thoracic aorta dissectiontad (TAD) and abdominal aortic aneurysm (ACA) are serious diseases that threaten human health. The prognosis is extremely poor. Tad is a single gene hereditary disease. Dozens of genes have been found to cause TAD disease. Many syndromes can be manifested as tat, such as Marfan's syndrome, Loeys-Dietz syndromes, DDS, Ehlers-Danlos syndrome.These diseases are vascular type Turner syndrome, et al. The disease often begins before the patient reaches adulthood. The mortality rate is very high. However, because the clinical phenotype is different in different diseases or the same disease, there are a few patients with mild clinical symptoms, and only in adulthood and even in middle age have TAD manifestations. These factors make it more difficult for clinicians to diagnose the etiology of TAD. The general age of onset of TAD is over 60 years old. It is a disease caused by many genes and other external factors. The main cause of elderly patients with AAA is hypertension. Smoking and atherosclerosis. But in young AAA patients, especially those with a family history, clinicians are often unable to provide etiological diagnosis, life guidance, fertility and genetic counseling. Researchers have been studying the genes that cause AAA, but the results have not been satisfactory. Some of the results are even contradictory. Like TAD, triple-A can be caused by multiple syndromes. It is difficult to diagnose the etiology. Whole Exome sequencingus can be sequenced to analyze all exons of the genome. The mutation of known pathogenic genes and even new ones can be found efficiently. Objective: to identify the pathogenic genes of aortic dissection and abdominal aortic aneurysm. Methods: three cases of Stanford B type aortic dissection were studied by WES technique. One patient with abdominal aortic aneurysm was sequenced. Results: two patients with Stanford B aortic dissection had FBN1 gene mutation of c. G 6953 A p. C2318Y and c. 4786 TMP. RJ596XG, and 1 case of Stanford B aortic dissection had PKD2 gene mutation. The TGFBR1 rs113605875 exon9cG1460A p. R487Q) gene was identified as the pathogenicity gene of AAA for the first time. The AAA pedigree caused by TGFBR1 gene mutation was reported for the first time. Conclusion: unlike the elderly patients with sporadic aortic dissection and abdominal aortic aneurysm, we suggest that the etiology of early onset patients should be studied. The identification of pathogenic genes is useful not only for clinical diagnosis, but also for clinical decision making, lifestyle guidance, drug therapy, regular screening, fertility and genetic counseling.
【學(xué)位授予單位】：南京大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R543.1
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本文編號(hào)：1664976