Institut de la Vision, Paris, France.
Curr Opin Neurol. 2012 Feb;25(1):42-9. doi: 10.1097/WCO.0b013e32834ef8b2.
Usher syndrome (USH) is the most prevalent cause of hereditary deafness-blindness in humans. In this review, we pinpoint new insights regarding the molecular mechanisms defective in this syndrome, its molecular diagnosis and prospective therapies.
Animal models wherein USH proteins were targeted at different maturation stages of the auditory hair cells have been engineered, shedding new light on the development and functioning of the hair bundle, the sound receptive structure. Improved protocols and guidelines for early molecular diagnosis of USH (USH genotyping microarrays, otochips and complete Sanger sequencing of the 366 coding exons of identified USH genes) have been developed. Approaches to alleviate or cure hearing and visual impairments have been initiated, leading to various degrees of functional rescuing.
Whereas the mechanisms underlying hearing impairment in USH patients are being unraveled, showing in particular that USH1 proteins are involved in the shaping of the hair bundle and the functioning of the mechanoelectrical transduction machinery, the mechanisms underlying the retinal defects are still unclear. Efforts to improve clinical diagnosis have been successful. Yet, despite some encouraging results, further development of therapeutic approaches is necessary to ultimately treat this dual sensory defect.
先天性耳聋-失明综合征（Usher 综合征，USH）是人类遗传性耳聋-失明最常见的原因。在这篇综述中，我们详细阐述了该综合征中缺陷的分子机制、分子诊断和潜在治疗方法的新见解。
构建了针对听觉毛细胞不同成熟阶段 USH 蛋白的动物模型，这为毛束（声音接收结构）的发育和功能提供了新的认识。已经开发出用于 USH 早期分子诊断的改良方案和指南（USH 基因分型微阵列、otochips 和已鉴定 USH 基因的 366 个编码外显子的完整 Sanger 测序）。已经开始采用各种方法来减轻或治愈听力和视力障碍，从而实现不同程度的功能恢复。
虽然正在阐明 USH 患者听力障碍的机制，特别是表明 USH1 蛋白参与毛束的形成和机械-电转导机制的功能，但视网膜缺陷的机制仍不清楚。改善临床诊断的努力已取得成功。然而，尽管取得了一些令人鼓舞的结果，但仍有必要进一步开发治疗方法，最终治疗这种双重感觉缺陷。
