Applying Genomic Sequencing in Pediatrics

描述（由申请人提供）：这项工作代表了将基因组测序带入儿科临床环境的团队努力。我们选择验证和研究5组儿童疾病的基因组测序，这些疾病在基因异质性的程度上，基因检测是昂贵和耗时的。我们将研究以下患者：1)双侧感觉神经性听力障碍，遗传性视网膜变性，核编码线粒体呼吸链疾病，心脏骤停/心源性猝死和智力残疾。我们的研究将整合到三个项目中（临床基因组研究、测序、测序数据的分析和解释、研究的伦理和社会心理影响），以开发识别和同意研究患者的工具，执行和解释测序数据，并向患者家属报告有用的信息。我们将验证我们识别临床重要发现的能力，以及我们识别偶然发现并确定哪些对家庭有用的能力。这项独特的研究将使我们能够预先与家庭、科学家和伦理学家合作，确定在检测前应该如何对患者进行咨询和教育，应该向个别家庭提供哪些数据，以及哪些教育工具将有助于理解检测的含义。此外，还有临床医生、诊断实验室

DESCRIPTION (provided by applicant): This work represents a team effort to bring genomic sequencing into a pediatric clinical setting. We have chosen to validate and study genomic sequencing for 5 groups of pediatric disorders that are genetically heterogeneous to the extent that gene by gene testing Is expensive and time consuming. We will study patients with 1) bilateral sensorineural hearing Impairment, Inherited retinal degenerations, nuclear encoded mitochondrial respiratory chain disorders, sudden cardiac arrest/sudden cardiac death and intellectual disability. Our studies will be Integrated across three projects (Clinical Genomic Studies; Sequencing, Analysis and Interpretation of Sequencing Data; and Ethical and Psychosocial Implications of Research) to develop the tools for identifying and consenting patients for study, carrying out and Interpreting the sequencing data and reporting back useful Information to the families of our patients. We will validate our ability to Identify clinically significant findings, as well as our ability to identify incidental findings and determine which o these will be useful to families. This unique study will allow us to work with families, scientist and ethicists up front, to determine how our patients should be counseled and educated before testing, what data should be provided back to Individual families, and what educational tools will help in understanding the Implications of the testing. In addition, the clinicians, diagnostic lab directors and scientists will develop the sequencing. Interpretative and bioinformatic tools necessary to accurately and thoughtfully extract the relevant data from our patient's genomes. We anticipate that at the end of this grant period. In concert with other centers carrying out similar work, genomic sequencing will be ready to be offered for diagnosis of pediatric disorders, with a clear view of the possible findings, and a plan for identification of clinically useful information. PUBLIC HEALTH RELEVANCE: Genetic disorders are highly prevalent in the pediatric population and contribution to a high percentage of morbidity and mortality, but diagnosis can be cumbersome and expensive. Genome sequencing offers the opportunity to carry out one test, with the ability to identify genetic causes of disease anywhere in the genome. This project promises to provide the tools to carry out and interpret genomic sequencing data.