Implementing genomic medicine in clinical care of deaf patients

在聋哑患者的临床护理中实施基因组医学

• 批准号: 8634091
• 负责人: XUE Z LIU
• 金额: $ 61.38万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-08 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8634091
• 关键词: Accounting; Affect; Age; Algorithms; Auditory; Bioinformatics; Biological; Biology; Birth; Caring; China; Clinic; Clinical; Clinical Management; Computerized Medical Record; Data; Databases; Defect; Diagnostic; Dideoxy Chain Termination DNA Sequencing; Disease; Environment; Epidemiologic Studies; Epidemiology; Ethnic Origin; Evaluation; Family; Frequencies; Gene Frequency; Gene Mutation; Genes; Genetic; Genetic Annotation; Genetic Counseling; Genetic Polymorphism; Genetic Variation; Genetic screening method; Genomics; Genotype; Health; Hearing; Hearing Impaired Persons; Hereditary Disease; Human; Individual; Infant; Inherited; Institutes; Knowledge; Laboratories; Lead; Link; Literature; Maps; Medical; Medicine; Meleagris gallopavo; Methods; Molecular; Molecular Epidemiology; Molecular Genetics; Mutation; Patient Care; Patients; Pattern; Pilot Projects; Population; Population Control; Process; Proteins; Reporting; Research Personnel; Resources; Source; System; Testing; Time; United States; Validation; Variant; base; clinical Diagnosis; clinical care; clinically relevant; clinically significant; cohort; deafness; ethnic difference; evidence base; exome sequencing; follow-up; genetic pedigree; hearing impairment; improved; knowledge translation; meetings; next generation sequencing; novel; patient population; proband; programs; public health relevance; research clinical testing; screening; segregation; therapeutic development

DESCRIPTION (provided by applicant): Hearing loss (HL) affects at least 30% of the population at some time in their lives. While HL has both genetic and environmental underpinnings, the genetic causes of hearing loss are estimated to account for 68% of cases expressed at birth and 55% of those expressed by the age of four. The identification of many genes for HL has dramatically improved the clinical diagnosis and management of deaf and hard-of-hearing families. However, current strategies for genetic testing for deafness are inadequate. Genetic testing currently focuses on testing only a few of the known genes and so in many cases, the genetic cause is never determined. The identification of numerous genes causing NSHL along with recent technological advances in "target-enrichment" methods and next generation sequencing (NGS) is now making possible molecular epidemiological studies of genetic deafness and a new wave of discoveries of the remaining genes for genetic diseases. The translation of this knowledge to patient care is, however, lagging behind. Currently, few available databases have useful evidence-based information concerning the clinical validity and clinical utility of genetic information for deafness patient management. There is an urgent need to bring comprehensive genomic information of individual patients into the "real world" clinical environment. We have collected a unique cohort of multiplex families derived from three unique sources from USA, China and Turkey, suitable for determination of molecular epidemiology of hereditary deafness and for new gene identification. We have established the Miami Otogenetic Program including the Molecular Genetic Laboratory and the Hereditary Hearing Loss Clinic. Importantly, as shown in our preliminary studies, we have shown that it is possible to analyze all deafness genes simultaneously on a single platform, excluded known causes of HL in 40% of the probands in our pilot studies and successfully identified three new genes in these small multiplex families using whole exome sequencing. Building on these preliminary data in this translational proposal we will complete three specific aims. 1: To determine molecular epidemiology of deafness-causing mutations in known NSHL genes by completing mutation screening of all genes causing NSHL in a large cohort of probands from different ethnic populations. 2: To identify new genes for non-syndromic hearing loss in those multiplex families found to be negative for all known deafness genes by whole exome sequence. 3: To create Genomic Deafness Database (GDD) and Personalized Sequence Profile (PSP) for care of deafness patients.

描述（由申请人提供）：听力损失（HL）在他们一生中的某个时候至少影响了30％的人口。尽管HL具有遗传和环境基础，但估计听力损失的遗传原因占出生时表达的病例的68％，而在四岁时表达的病例的55％。许多HL基因的鉴定已大大改善了聋哑和听力障碍家庭的临床诊断和管理。但是，目前的聋哑基因检测策略不足。基因测试目前仅着重于测试少数已知基因，因此在许多情况下，永远无法确定遗传原因。鉴定了引起NSHL的许多基因以及“靶入目标”方法的最新技术进步和下一代测序（NGS）现在，可以使遗传性耳聋的分子流行病学研究以及其余基因发现遗传疾病的新发现。然而，将这种知识转换为患者护理是落后的。当前，很少有可用的数据库具有有关遗传信息的临床有效性和临床实用性的有用的基于证据的信息，用于聋哑患者管理。迫切需要将个别患者的全面基因组信息带入“现实世界”临床环境。我们收集了来自美国，中国和土耳其的三个独特来源的独特多重家族，适合确定遗传性耳聋的分子流行病学和新的基因鉴定。我们已经建立了迈阿密输肠发育计划，包括分子遗传实验室和遗传性听力损失诊所。重要的是，如我们的初步研究所示，我们已经表明，可以在单个平台上同时分析所有聋哑基因，在我们的初步研究中40％的概率中排除了HL的已知原因，并成功地鉴定了这些小型多重族中的三个新基因。在本翻译建议中，我们将完成三个特定目标。 1：确定已知NSHL基因引起聋哑突变的分子流行病学，通过完成从不同种族种群的大量探险中引起NSHL的所有基因的突变筛选。 2：确定那些多重多重族中非综合性听力损失的新基因，发现整个外显子组序列对所有已知的耳聋基因均为阴性。 3：创建基因组聋哑数据库（GDD）和个性化序列概况（PSP）来护理聋哑患者。