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：
9898441
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 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9898441
关键词：
Acute Adult Affect Age Aneurysm Aortic Aneurysm Aortic Valve Insufficiency Aortic Valve Stenosis 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 Heterogeneity Genetic Predisposition to Disease Genetic study Genotype Goals Hospitalization Individual Intervention Lead Left Lesion Life Medical Morbidity - disease rate 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 heterogeneity clinical phenotype clinical predictors clinically relevant cohort de novo mutation 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.

二叶式主动脉瓣 (BAV) 可因主动脉瓣狭窄导致过早死亡，主动脉瓣关闭不全或胸主动脉瘤导致急性主动脉夹层（TAAD）。 BAV 的遗传原因仍然很大程度上未知，因为大量的 BAV 相关并发症的遗传和临床异质性。我们确定罕见的拷贝数变异 (CNV) 在 BAV 患者中显着丰富经历过早期出现的临床并发症。我研究的总体目标是识别导致 BAV 及其相关疾病的致病基因变异并发症，并建立与每种并发症相关的临床表型新基因。我的提案的具体目标是：1）描述一组 BAV 的特征患有严重和早发并发症的患者，2) 识别罕见的 CNV 与严重的 BAV 相关并发症相关，3) 识别罕见的外显子组具有严重表型或独特临床特征的患者的序列变异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研究 BAV 疾病的病因学，也可能有助于风险分层或临床有关 BAV 患者监测和选择性干预的决策。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Copy-number variation in congenital heart disease.

先天性心脏病的拷贝数变异。

DOI：
10.1016/j.gde.2022.101986
发表时间：
2022-10-03
期刊：
Current opinion in genetics & development
影响因子：
4
作者：
L. Ehrlich;Siddharth K. Prakash
通讯作者：
Siddharth K. Prakash

Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease.

基因组变异的综合分析揭示了候选单倍体不足基因与先天性心脏病的新关联。

DOI：
发表时间：
2021-07
期刊：
影响因子：
4.5
作者：
Audain, Enrique;Wilsdon, Anna;Breckpot, Jeroen;Izarzugaza, Jose M G;Fitzgerald, Tomas W;Kahlert, Anne;Sifrim, Alejandro;Wünnemann, Florian;Perez;Abdul;Bak, Mads;Bassett, Anne S;Benson, D Woodrow;Berger, Fe
通讯作者：
Berger, Fe

Misclassification of bicuspid aortic valves is common and varies by imaging modality and patient characteristics.

二叶式主动脉瓣的错误分类很常见，并且因成像方式和患者特征而异。

DOI：
发表时间：
2019
期刊：
影响因子：
0
作者：
Cramer, Peyton M;Prakash, Siddharth K
通讯作者：
Prakash, Siddharth K

Rare Genomic Copy Number Variants Implicate New Candidate Genes for Bicuspid Aortic Valve.

罕见的基因组拷贝数变异暗示二尖瓣主动脉瓣的新候选基因。

DOI：
发表时间：
2023-10-24
期刊：
影响因子：
0
作者：
Carlisle, Steven G;Albasha, Hasan;Michelena, Hector;Sabate;Bianco, Lisa;De Backer, Julie;Mosquera, Laura Muiño;Yetman, Anji T;Bissell, Malenka M;Andreassi, Maria Grazia;Foffa, Ilenia;Hui, Dawn S;Caffarelli, Anthony;Kim, Yuli Y;Gu
通讯作者：
Gu

TGFBR1 Rare Variant Associated With Thoracic Aortic Aneurysm, Double Chamber Left Ventricle, Coronary Anomaly, and Inducible Ventricular Tachycardia.

TGFBR1 罕见变异与胸主动脉瘤、双腔左心室、冠状动脉异常和诱发性室性心动过速相关。

DOI：
发表时间：
2020
期刊：
影响因子：
0
作者：
Bravo;Marah, Naddi B;Raghunathan, Deepa;Napierkowski, Steven;Ekeruo, Ijeoma A;Kitkungvan, Danai;Milewicz, Dianna M;Smalling, Richard W;Prakash, Siddharth K
通讯作者：
Prakash, Siddharth K