SEQuencing a Baby for an Optimal Outcome (SEQaBOO)

对婴儿进行测序以获得最佳结果 (SEQaBOO)

• 批准号: 9021176
• 负责人: Cynthia Casson Morton
• 金额: $ 77.01万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9021176
• 关键词: Address; Algorithms; Area; Attitude; Bioinformatics; Birth; Boston; Caring; Child; Childhood; Chromosomes; Clinical; Cochlear Implants; Congenital Abnormality; DNA Sequence; DNA Sequence Alteration; Data Set; Detection; Development; Diagnosis; Diagnostic; Disease; Ear; Early Intervention; Enrollment; Etiology; Eye; Family; Family member; Foundations; General Hospitals; Genes; Genetic; Genetic Predisposition to Disease; Genetic screening method; Genome; Genomic approach; Genomic medicine; Genomics; Goals; Health; Health Status; Hearing; Hospitals; Human Resources; Individual; Infant; Institutes; Interview; Knowledge; Laboratories; Language Development; Libraries; Life; Massachusetts; Medical Records; Medicine; Methodology; Methods; Mutation; Neonatal; Neonatal Screening; Newborn Infant; Outcome; Output; Parents; Patients; Pediatric Hospitals; Phase; Physicians; Quality of life; Research; Research Personnel; Risk; Role; Screening Result; Sequence Analysis; Societies; Speech Development; Structure; Sum; Surveys; Technology; Testing; Therapeutic Intervention; Translating; Variant; Virus Diseases; Woman; clinical Diagnosis; clinical application; clinical care; clinical practice; cohort; cost effective; data sharing; disability; exome sequencing; follow-up; genetic disorder diagnosis; genetic information; genetic technology; genetic variant; genome sequencing; genome-wide; genomic data; hearing impairment; hearing screening; improved; innovation; insight; malformation; neonate; new technology; next generation; public health relevance; research clinical testing; screening; social; standard of care; tool; whole genome

 DESCRIPTION (provided by applicant): SEQaBOO (SEQuencing a Baby for an Optimal Outcome) will translate high-throughput genomic approaches into routine newborn screening for hearing loss (HL). The project will enroll approximately 500 newborns that do not pass their initial newborn hearing screen and their parents for genomic sequence analysis. Until recently, clinical diagnosis of congenital defects without an overt anatomical malformation, such as hearing loss, was profoundly limited. Today, congenital HL and other subtle birth defects are recognized in newborns, allowing early interventions that limit life-long disabilities. Development of next generation DNA sequencing technologies provides a new opportunity for researchers and clinicians dedicated to improving the lives of newborns with birth defects to investigate whether genetic etiologies of congenital defects can be more accurately and efficiently defined and whether improved genetic diagnosis translates into superior clinical care. In this project we aim to address this challenge by assessing the clinical impact of genomic data in newborns with congenital HL. For newborns in whom no pathogenic mutation is identified via exome sequencing, alternative genomic approaches will be used to explore comprehensively the full mutational spectrum across the genome. Analytic pipelines will be developed to provide automated and accurate clinical interpretation of genomic variants. When appropriate, genetic information will be returned to parents and physicians for early intervention purposes. Although diagnosed in the early neonatal period and not life threatening, HL requires a number of adjustments by the family and patient to optimize quality of life. In some instances, cochlear implants can restore hearing to near normal levels. Other therapeutic interventions for congenital HL are under development. As there are a remarkable number of different etiologies of congenital HL that range from genetic mutation to viral infection, we surmise that appropriate therapies may vary depending on precise etiology. Genetic causes of HL are highly heterogeneous and mutations in >115 genes have already been identified. In this proposal, we will test the hypothesis that rapid discovery of the exact cause of a newborn's HL will benefit management and therapeutic interventions. Annually we will survey the cohort of children to ascertain general health, including speech and language development in addition to hearing status, and parental attitudes on genomic sequencing. In sum, we will analyze and assemble genomic datasets, perform clinical genomic research of HL identifiable through newborn screening and explore implications of integration of genomic sequencing into newborn screening. All of this will inform the impact of genomic sequencing on the care and management of newborns with congenital HL and allow us to investigate factors associated with our society's acceptance of this new technology for "optimal outcome" of a newborn baby.

 描述（由申请人提供）：SEQaBOO（SEQuencing a Baby for an Optimal Outcome）将把高通量基因组方法转化为常规新生儿听力损失（HL）筛查。该项目将招募大约 500 名未通过初次新生儿听力筛查的新生儿及其父母进行基因组序列分析。直到最近，对没有明显解剖畸形的先天性缺陷（例如听力损失）的临床诊断仍然非常有限。如今，先天性 HL 和其他细微的出生缺陷在新生儿中得到了认可，从而可以进行早期干预以限制终身残疾。发展 下一代 DNA 测序技术的发展为致力于改善出生缺陷新生儿生活的研究人员和临床医生提供了新的机会，以研究是否可以更准确、更有效地确定先天性缺陷的遗传病因，以及改进的基因诊断是否可以转化为优质的临床护理。在这个项目中，我们的目标是通过评估基因组数据对患有先天性 HL 的新生儿的临床影响来应对这一挑战。对于通过外显子组测序未发现致病性突变的新生儿，将使用替代基因组方法来全面探索整个基因组的完整突变谱。将开发分析管道以提供基因组变异的自动化和准确的临床解释。在适当的情况下，遗传信息将返回给父母和医生用于早期干预目的。尽管 HL 在新生儿早期被诊断出来且不会危及生命，但仍需要家人和患者进行一系列调整以优化生活质量。在某些情况下，人工耳蜗可以将听力恢复到接近正常水平。针对先天性 HL 的其他治疗干预措施正在开发中。由于先天性 HL 有多种不同的病因，从基因突变到病毒感染，我们推测适当的治疗方法可能会根据具体的病因而有所不同。 HL 的遗传原因具有高度异质性，并且已鉴定出超过 115 个基因的突变。在本提案中，我们将检验以下假设：快速发现新生儿 HL 的确切原因将有利于管理和治疗干预。每年我们都会对儿童群体进行调查，以确定总体健康状况，包括言语和语言发育、听力状况以及父母对基因组测序的态度。总之，我们将分析和组装基因组数据集，对可通过新生儿筛查识别的 HL 进行临床基因组研究，并探索将基因组测序整合到新生儿筛查中的意义。所有这些都将揭示基因组测序对先天性 HL 新生儿护理和管理的影响，并使我们能够调查与社会接受这项新技术以实现新生儿“最佳结果”相关的因素。