Confirmatory Screening for Congenital Non-Syndromic Genetic Hearing Loss Using Ta

使用 Ta 确认先天性非综合征性遗传性听力损失筛查

• 批准号: 8455986
• 负责人: Arindam Bhattacharjee
• 金额: $ 20.05万
• 依托单位: PARABASE GENOMICS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2013-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8455986
• 关键词: Address; Adult; Adverse effects; Affect; Age; Aminoglycoside Antibiotics; Aminoglycosides; Antibiotics; Back; Base Sequence; Biological Assay; Birth; Blood specimen; Body Fluids; Body cavities; Businesses; Cheek structure; Child; Clinical; Clinics and Hospitals; Collaborations; Collecting Cell; Collection; Country; Cytomegalovirus; Cytomegalovirus Infections; DNA; DNA Sequence; Data; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Differential Diagnosis; Disadvantaged; Disease; Early Diagnosis; Early treatment; Exposure to; Family; Future; Genes; Genetic; Genetic Predisposition to Disease; Genetic Screening; Genomics; Genotype; Health Care Costs; Health Personnel; Healthcare; Hearing; Hearing Tests; Human; Individual; Infant; Infection; Intellectual Property; Lead; Lesion; Low Birth Weight Infant; Measures; Methodology; Methods; Mitochondria; Mutation; Neonatal Intensive Care Units; Neonatal Screening; Newborn Infant; Organism; Paper; Parents; Patients; Performance; Pharmaceutical Preparations; Phase; Phenotype; Physicians; Population; Positioning Attribute; Pregnancy; Process; Professional counselor; Protocols documentation; Resources; Right-On; Risk; Saliva; Sampling; Sensitivity and Specificity; Services; Specimen; Techniques; Testing; Time; Usher Syndrome; Validation; Virginia; Virus Diseases; Whole Blood; base; body cavity; commercialization; congenital cytomegalovirus; congenital infection; cost effective; design; follow-up; genome sequencing; hearing impairment; hearing screening; high risk; high risk infant; medical schools; next generation sequencing; non-genetic; novel; prototype; public health relevance; sample collection; screening; tool

DESCRIPTION (provided by applicant): Approximately 8,000 children in the USA are born each year with some form of hearing loss severe enough to require special services. Half of these are genetic in origin covering several hundred different regions in the genome where mutations affect the hearing process. One example of genetic predisposition makes some people more likely to develop hearing loss after taking certain antibiotic medications. Infants may also be born with hearing loss caused by a viral infection like cytomegalovirus (CMV) that was acquired during pregnancy. Newborns in the neonatal intensive care units are more likely to suffer from hearing loss as a toxic side effect of the antibiotics which are frequently administered. It is very challenging, while extremely important, to understand the cause of the disease and its treatment. The current approach of audiometric screening doesn't provide the genetic etiology, and the single gene sequencing method used to compliment this is costly, time consuming and impractical, requiring a large blood sample that cannot be easily obtained safely from an infant. We are developing a test using massively parallel DNA sequencing [Next Generation Sequencing (NGS)] methodology that can address the deficiencies of current testing and be used as a routine second-tier newborn screening tool in high-risk patients identified by current audiometric hearing screening. The test can also be used as a diagnostic for individuals with post lingual hearing loss for the identification of disease-causing loci. Such NGS sequencing panel-based screening and diagnostic methodologies are currently not available from a commercial company or for addressing the needs of newborns. Such commercial NGS-based diagnostic methods can be rapidly expanded throughout the country as a service, permitting quick diagnostic decisions, and have the potential to reduce healthcare costs by avoiding diagnostic delays. The newborn hearing screening protocols that are currently in use can result in over half of newborns who fail the screening test to be lost to follow-up and do not address the problem of congenital infections that cause hearing loss. Our first Specific Aim is to make this test accurate and appropriate for newborns and therefore we will focus on the right specimen collection strategy so the highest sensitivity and specificity is reached. In our second Specific Aim we will focus on a comprehensive gene panel addressing all relevant genetic loci and CMV specific panel in a single test and make it robust and accurate. The resulting prototype will be a valuable second tier-screening and diagnostic tool that will lead to a test that will address the needs of these high-risk infants. It will help healthcare providers, patients, and thei families to understand the precise cause of the hearing loss, and to plan accordingly. Our test is unique in that it simultaneously screens and/or diagnoses hundreds of these conditions at once from a single sample, providing more comprehensive information to families and their physicians and yet affordable and provide access to the associated data.

描述（由申请人提供）：美国每年约有8，000名儿童出生时患有某种形式的听力损失，严重到需要特殊服务。其中一半是基因起源，覆盖基因组中数百个不同的区域，突变影响听力过程。遗传易感性的一个例子是，一些人在服用某些抗生素药物后更容易患上听力损失。婴儿出生时也可能患有由病毒感染引起的听力损失，如妊娠期间获得的巨细胞病毒（CMV）。新生儿重症监护病房的新生儿更有可能遭受听力损失，这是频繁使用的抗生素的毒副作用。这是非常具有挑战性的，虽然非常重要，了解疾病的原因和治疗。目前的听力筛查方法不能提供遗传病因学，用于补充这一点的单基因测序方法成本高，耗时且不切实际，需要大量的血液样本，无法从婴儿中安全地获得。我们正在开发一种使用大规模并行DNA测序[下一代测序（NGS）]方法的测试，该方法可以解决当前测试的缺陷，并可用作通过当前听力筛查确定的高危患者的常规二级新生儿筛查工具。该测试也可用于诊断舌后听力损失的个体，以识别致病基因座。这种基于NGS测序组的筛查和诊断方法目前无法从商业公司获得或用于解决新生儿的需求。这种基于NGS的商业诊断方法可以作为一种服务在全国范围内迅速扩展，从而允许快速诊断决策，并且具有通过避免诊断延迟来降低医疗保健成本的潜力。目前使用的新生儿听力筛查方案可能导致超过一半的新生儿未能通过筛查测试而无法随访，并且无法解决导致听力损失的先天性感染问题。我们的第一个具体目标是使该检测准确且适用于新生儿，因此我们将专注于正确的标本采集策略，以达到最高的灵敏度和特异性。在我们的第二个具体目标，我们将专注于一个全面的基因面板解决所有相关的遗传位点和CMV特异性面板在一个单一的测试，使其强大和准确。由此产生的原型将是一个有价值的第二级筛查和诊断工具，将导致一个测试，将解决这些高危婴儿的需要。它将帮助医疗服务提供者、患者及其家属了解听力损失的确切原因，并做出相应的计划。我们的测试是独一无二的，因为它同时筛选和/或诊断数百个这些条件一次从一个单一的样本，提供更全面的信息，家庭和他们的医生，但负担得起的，并提供访问相关的数据。