Genotype-Phenotype Associations in Pediatric Cardiomyopathy

小儿心肌病的基因型-表型关联

基本信息

批准号：
8826164
负责人：
STEVEN EDWARD LIPSHULTZ
金额：
$ 209.26万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8826164
关键词：
Adult Age of Onset Age-Years Architecture Bioinformatics Canada Cardiac Cardiomyopathies Cessation of life Child Childhood Clinical Clinical Data Cohort Studies Companions DNA Data Data Analyses Data Collection Data Set Developing Countries Development Diagnosis Diagnostic Dilated Cardiomyopathy Disease Employee Strikes Enrollment Extracellular Matrix Family Fibrosis Frequencies Functional disorder Funding Gene-Modified Genes Genetic Genome Genomics Genotype Goals Grouping Heart Transplantation Heart failure Hereditary Disease Hypertrophic Cardiomyopathy Hypertrophy Individual Infant Knowledge Left Malignant - descriptor Morbidity - disease rate Mutation Myocardium Myopathy National Heart, Lung, and Blood Institute Obstruction Outcome Pathway interactions Patient risk Patients Phenotype Population Prevalence Prevention Proteins Registries Relative Risks Research Personnel Resolution Resources Restrictive Cardiomyopathy Risk Severity of illness Single Nucleotide Polymorphism Specimen Stratification Systems Biology Testing Therapeutic Intervention Thick Time Transcript Translations Transplantation Treatment outcome Variant Ventricular Ventricular Function base clinical phenotype cohort disease-causing mutation exome exome sequencing gene interaction genetic analysis genetic association genetic information genetic variant heart metabolism improved innovation insight mortality novel novel therapeutic intervention outcome forecast rare variant repository tool

项目摘要

DESCRIPTION (provided by applicant): Pediatric cardiomyopathy is a heterogeneous genetic disease with high morbidity and mortality in which children often present with fulminant disease leading to death or transplant. The long term goal of this project is to identify the genetic factors that determine the development and progression of cardiomyopathy in order to improve prevention, surveillance, early management, and prognosis. The specific aims of this study are 1) to identify the disease causing and disease associated genetic variants underlying pediatric cardiomyopathy in a carefully phenotyped cohort and 2) to identify genotype-phenotype correlations that allow for risk stratification and improve management and therapy. Exome sequencing will be used as part of a tiered genetic analysis in a large cohort of pediatric cardiomyopathy subjects with systolic (dilated cardiomyopathy) or diastolic (hypertrophic or restrictive cardiomyopathy) dysfunction. This study will significantly increase our understanding of pediatric cardiomyopathy by defining the prevalence of mutations in genes known to cause cardiomyopathy as well as identifying novel disease causing genes in the pediatric population. Genetic association tests will identify variants that modify disease. Novel bioinformatics and systems biology applications for interpretation of exome level genetic information will contribute fundamental knowledge and technical innovation to the translation of genomic data to clinical utility. These aims will provide critical genetic architecture data, identify variants with large effects, and enable genotype-phenotype correlations necessary for advancing management and therapy.

描述（由申请人提供）：小儿心肌病是一种异质遗传疾病，具有高发病率和死亡率，儿童经常出现暴发性疾病，导致死亡或移植。该项目的长期目标是确定确定心肌病发展和进展的遗传因素，以改善预防，监视，早期管理和预后。这项研究的具体目的是1）确定疾病和疾病相关的遗传变异，其基础小儿心肌病的遗传变异和经过精心表型的队列和2）识别基因型 - 表现型相关性，从而允许风险分层并改善管理和治疗。在大量的小儿心肌病与收缩期（膨胀心肌病）或舒张期（肥大或限制性心肌病）功能障碍的小儿心肌病学科中，外显子组测序将被用作分层遗传分析的一部分。这项研究将通过定义已知会引起心肌病的基因的普遍性以及鉴定出新的疾病引起小儿种群的基因，从而大大提高我们对小儿心肌病的理解。遗传关联测试将确定改变疾病的变体。新颖的生物信息学和系统生物学应用于解释外来水平遗传信息的应用程序将为将基因组数据转换为临床实用程序的基本知识和技术创新。这些目的将提供关键的遗传结构数据，确定具有较大影响的变体，并启用用于推进管理和治疗所需的基因型 - 表型相关性。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Genetic Causes of Cardiomyopathy in Children: First Results From the Pediatric Cardiomyopathy Genes Study.

儿童心肌病的遗传原因：小儿心肌病基因研究的第一个结果。

DOI：
10.1161/jaha.120.017731
发表时间：
2021-05-04
期刊：
Journal of the American Heart Association
影响因子：
5.4
作者：
Ware SM;Wilkinson JD;Tariq M;Schubert JA;Sridhar A;Colan SD;Shi L;Canter CE;Hsu DT;Webber SA;Dodd DA;Everitt MD;Kantor PF;Addonizio LJ;Jefferies JL;Rossano JW;Pahl E;Rusconi P;Chung WK;Lee T;Towbin JA;Lal AK;Bhatnagar S;Aronow B;Dexheimer PJ;Martin LJ;Miller EM;Sleeper LA;Razoky H;Czachor J;Lipshultz SE;Pediatric Cardiomyopathy Registry Study Group
通讯作者：
Pediatric Cardiomyopathy Registry Study Group

Toward Personalized Medicine: Does Genetic Diagnosis of Pediatric Cardiomyopathy Influence Patient Management?

走向个性化医疗：小儿心肌病的基因诊断是否会影响患者管理？