Genetic Basis of Early Onset Bicuspid Aortic Valve Disease

早发二尖瓣主动脉瓣疾病的遗传基础

基本信息

批准号：
9290031
负责人：
SIDDHARTH KUMAR PRAKASH
金额：
$ 38.5万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-05 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9290031
关键词：
Acute Adult Affect Age Aneurysm Aortic Aneurysm Aortic Valve Insufficiency Aortic Valve Stenosis Calcified Candidate Disease Gene Cardiac Cardiovascular Diseases Cessation of life Characteristics Child Clinical Clinical Research Collaborations Communities Congenital Heart Defects Copy Number Polymorphism Counseling DNA Data Disease Dissection Early Intervention Eligibility Determination Etiology Event Family Family member Family psychotherapy Frequencies Genes Genetic Genetic Predisposition to Disease Genetic study Genotype Goals Heterogeneity Hospitalization Individual Intervention Lead Left Lesion Life Medical Morbidity - disease rate Mutation Natural History Operative Surgical Procedures Outcome Parents Pathway interactions Patients Penetrance Phenotype Population Predictive Value Recurrence Research Research Personnel Risk Risk stratification SNP array Sampling Side Subgroup Testing Thoracic Aortic Aneurysm Time Variant aortic valve aortic valve disorder aortic valve replacement base bicuspid aortic valve calcification clinical decision-making clinical phenotype clinical predictors clinically relevant cohort dosage early experience early onset exome exome sequencing genetic analysis genetic linkage analysis genetic variant improved insight member mortality neonate novel older patient pediatric patients phenotypic data premature proband prophylactic rare variant repaired screening segregation success young adult

项目摘要

Bicuspid Aortic Valves (BAV) can cause premature deaths due to aortic stenosis, aortic regurgitation or Thoracic Aortic Aneurysms leading to acute aortic Dissections (TAAD). The genetic causes of BAV remain largely unknown due to the substantial genetic and clinical heterogeneity of complications related to BAV. We determined that rare Copy Number Variants (CNVs) are significantly enriched in BAV patients who experienced early onset clinical complications. The overall goal of my research is to identify causal genetic variants that are responsible for both the BAV and its complications, and to establish the clinical phenotypes that are associated with each new gene. The specific aims of my proposal are: 1) to characterize a cohort of BAV patients with severe and early onset complications, 2) to identify rare CNVs that are associated with severe BAV-related complications and 3) to identify rare exome sequence variants in patients with severe phenotypes or distinctive clinical features who have available parents or affected relatives. Our discoveries could provide new insights into the etiology of BAV disease and may also be useful for risk stratification or clinical decision-making about surveillance and elective interventions for BAV patients.

双刺主动脉瓣（BAV）可能导致主动脉狭窄引起的过早死亡，主动脉反流或胸动脉瘤，导致急性主动脉夹层（TAAD）。由于实质性与BAV有关的并发症的遗传和临床异质性。我们确定了这一点 BAV患者的稀有拷贝数变体（CNV）显着丰富经历了早期发作并发症。我的研究的总体目标是识别负责BAV及其构成的因果遗传变异并发症，并建立与每种相关的临床表型新基因。我的提议的具体目的是：1）表征一系列BAV 患有严重和早期发作并发症的患者，2）确定稀有的CNV 与严重的BAV相关并发症相关，3）识别稀有的外显子严重表型或独特临床特征的患者的序列变体有可用的父母或受影响的亲戚。我们的发现可以提供新的见解进入BAV疾病的病因，也可能对风险分层或临床有用关于BAV患者的监视和选择性干预的决策。