The Otopathology of Hearing Loss: Genotype-Phenotype Correlation in Human TB

描述(由申请人提供)：将耳病理学分析与现有综合征和非综合征内耳疾病的基因筛查相结合是内耳研究所为NIDCD的耳病理学研究合作网络做出贡献的目标。这些相关性的价值在于将基因诊断与更好地了解疾病进展和病理后遗症，以及确定未来治疗的目标，以及更重要的是改进遗传咨询。由于几乎完全缺乏与内耳疾病相关的人类活检材料，这种联系在很大程度上仍然未知，而这些信息的唯一来源是现有的死后颞骨收集。为此，我们开发了从现有档案颞骨中提取和分析生物材料(DNA和蛋白质)的技术，相关的临床数据已编目并可用。在这里，我们提出了几个特定的目标，旨在识别我们联盟成员收藏的现有颞骨标本中潜在的基因突变/遗传变异，目的是建立基因/耳病理学表型相关性。对于任何已知的内耳遗传性疾病来说，这一点并不是一致的，这项提议的成功结果有望为希望将内耳疾病的病因与其耳部病理结果联系起来的临床医生和研究人员提供更多的资源。

DESCRIPTION (provided by applicant): Correlating otopathological analysis with genetic screening for existing syndromic and non-syndromic inner ear diseases is the goal of the House Ear Institute's contribution to the NIDCD's Otopathology Research Collaboration Network. The value of these correlations lies in connecting genetic diagnosis with a better understanding of disease progression and pathological sequelae, as well as the identification of targets for future treatment and, importantly, improved genetic counseling. Because of an almost complete lack of human biopsy material associated with inner ear disease, such connections remain largely unknown, and the only source of this information is the existing post-mortem temporal bone collections. For this reason, we have developed techniques for extracting and analyzing biological material (DNA and protein) from existing archival temporal bones for which relevant clinical data is cataloged and available. Here, we propose several Specific Aims designed to identify the underlying genetic mutations/genetic variants in existing temporal bone collections housed by members of our consortium, with the purpose of establishing a genotype/otopathology phenotype correlation. This has not been done consistently for any of the known genetic disorders of the inner ear, and the successful outcome of this proposal promises to provide an enhanced resource for the clinician and researcher who wish to link the etiology of inner ear disease with its otopathological outcome.