Identification Of Disease-Causing Mutations Of Thoracic Aorta Dissection And Abdominal Aorta Aneurysm By Whole Exome Sequencing

Background:Thoracic aorta dissection(TAD)and abdominal aorta aneurysm(AAA)are serious diseases to health.These two diseases ususally progresses without symptoms.Once aorta ruptures,the prognosis is extremely bad.TAD is a monogenetic disorder.It has been found that dozens of gene mutations can lead to the occurrence of TAD.TAD can be a complication of multiple systemic diseases,such as Marfan syndrome,Loeys-Dietz syndrome(LDS),Ehlers-Danlos syndrome,Turner syndrome.Patients with these systemic diseases usually occur fatal complications before adulthood.However,due to clinical phenotypes vary in different diseases or the same disease,there are a small number of patients with mild clinical symptoms suffering TAD in middle age.These factors have increased the difficulty for clinicians to make an accurate diagnose of the etiology of TAD.AAA affect 5-8%of men above 60 years of age.AAA is considered a multifactorial disorder in which both environmental and genetic factor.It is generally believed that the most important risks of elderly AAA patients are hypertension,smoking and atherosclerosis.However,early-onset AAA patients,especially those with family history,often can not be provided the etiology,life guidance and genetic counseling.In the recent 30 years,scholars have been studying the pathogenic genes of AAA,but the results are unsatisfactory.Some results even contradict each other.Like TAD,AAA can also be caused by multiple systemic diseases,which make it difficult to diagnose correctly.The whole exon sequencing(WES)can sequence the entire exons of genome,detecting mutations of known pathogenic genes or new pathogenic genes efficently.Object:To identify pathogenic of thoracic aortic dissection and abdominal aortic aneurysm.Methods:Three Stanford type B aortic dissection patients and one abdominal aortic aneurysm patient were analyzed by WES technique.Results:We found two mutations of the FBN1 gene c.G6953A(p.C2318Y)and c.4786T(p.R1596X)in two patients with Stanford type B aortic dissection.PKD2 gene mutation c.C1774T(p.R592X)was found in a Stanford type B aortic dissections.Also,we firstly identify that TGFBR1(rs113605875,exon9,c.G1460A,p.R487Q)is a pathogenic gene of AAA,and report an AAA family caused by this mutations.Conclusions:In contrast to patients with late-onset TAD or AAA,we recommend that patients with early-onset Stanford type B patients should identify the etiology of TAD or AAA and,if necessary,the use of WES aid to clarify the cause.Mutation identification not only helps clinical make an accurate diagnosis,but also aid to clinical decision-making,lifestyle guidance,drug therapy,regular screening,fertility and genetic counseling.