GENETIC ANALYSIS OF DOMINANT PROGRESSIVE HEARING LOSS

显性进行性听力损失(DPHL)起病于儿童时期和 在成年后发展为严重到严重的丧失。造成这一现象的原因 听力损失是未知的，目前还没有治疗方法来阻止 进步。家系内部有普遍的表型一致性，但 不同家庭在年龄等特征上存在显著差异 发病、进展速度、最初受影响的频率和前庭 参与其中。这种变异反映了基因的异质性 现在已经在我们的实验室和其他地方得到了证实。遗传异质性 将使进展性糖尿病的病因和治疗研究复杂化 听力损失，因为不同的基因可能会有不同的 致病机制。这个项目将利用密集的DNA图谱 微卫星重复序列多态技术用于DPHL和DPHL基因定位 完整的听力学和前庭评估将用于 确定它们的表型。DPHL基因的定位 连锁分析有两个重要作用。首先，特定的基因 在给定的家庭中导致听力损失的相关因素可以被识别 通过它的链接结果。因此，来自拥有相同数据的个人的数据 可以对听力损失的类型进行分类，以便进一步研究其机制 和治疗。其次，基因定位是迈向 基因本身的特征。从长远来看，这些数据 作为该项目的一部分收集将有助于促进进一步的研究 可以防止听力逐渐恶化的治疗方法。

Dominant Progressive Hearing Loss (DPHL) has its onset in childhood and progresses to severe to profound loss in adulthood. The cause of the hearing loss is unknown, and there is currently no treatment to stop the progression. There is general phenotypic consistency within families, but marked differences between families for such characteristics as age of onset, rate of progression, frequencies initially affected, and vestibular involvement. This variation reflects the genetic heterogeneity which has now been proven in our laboratory and in others. Genetic heterogeneity will complicate research into the causes and treatment of progressive hearing loss, since different genes can be expected to have different pathogenic mechanisms. This project will utilize a dense map of DNA microsatellite repeat polymorphisms to localize the genes for DPHL and complete audiological and vestibular evaluations will be used to characterize their phenotypes. Localization of the genes for DPHL through linkage analysis has two important effects. First, the particular gene involved in causing the hearing loss in a given family can be identified by its linkage results. From this, data from individuals with the same type of hearing loss can be grouped for further research into mechanism and treatment. Secondly, gene localization is the first step toward characterization of the gene itself. Over the longer term, the data collected as part of this project will help foster further research into therapies that may prevent the gradual deterioration of hearing.