GENETIC STUDIES OF USHER SYNDROME

亚瑟综合症的遗传学研究

• 批准号: 6589747
• 负责人: William J Kimberling
• 金额: $ 16.33万
• 依托单位: FATHER FLANAGAN'S BOYS' HOME
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6589747
• 关键词: chromosome aberrations; clinical research; congenital deafness; disease /disorder classification; family genetics; gel electrophoresis; gene expression; gene frequency; gene mutation; genetic disorder diagnosis; genetic markers; genetic polymorphism; genetic screening; genotype; human subject; linkage mapping; molecular cloning; molecular genetics; northern blottings; polymerase chain reaction; retinitis pigmentosa; single strand conformation polymorphism; vestibular apparatus

Usher Syndrome is a hereditary disorder that causes hearing loss (HL) and retinitis pigmentosa (RP). The three major clinical types, Usher syndrome types I, II and II, are distinguished by severity of hearing loss and by presence or absence of vestibular dysfunction. Type I patients have severe hearing loss, RP, and vestibular dysfunction. Type I patients have severe hearing loss, RP, and vestibular dysfunction. Type III is distinguishable from types I and II by a progressive HL and variable vestibular deficit. At least ten distinct genetic loci are now believed to be associated with the three clinical types of Usher syndrome. We have collected the world's largest series of Usher families, a unique resource suitable for the studies proposed in this project. We propose to work towards a clarification of the problem of heterogeneity by testing hypotheses relating to the existence of all Usher loci and by estimating the relative contribution of each to the overall frequency of Usher syndrome. In addition, we propose to determine the distribution of mutations in MYO7A and USH2A, to identify and characterize the genes causing Usher types IIb, Ia, Id/f, Ie, and III, and to localize the gene for Usher type II c and any other new Usher genes uncovered by this research. Since Usher Syndrome results in the loss of the two most vital human senses, the burden to patients with this disorder is tremendous. It acts to isolate them from the rest of society and reduces their ability to act independently. Close to 1 in 15,000 individuals are affected with Usher Syndrome. The capability of Usher subtype diagnosis disorder will be enhanced leading to more accurate genetic counseling. A better understanding of the underlying etiology of Usher Syndrome is a critical first step towards the development of effective therapy. Usher syndrome offers a way of studying how the two major senses are related and answers to questions regarding the etiology of Usher Syndrome will reveal important and novel information about the developmental, metabolic and/or regulatory pathways common to normal retinal and auditory function.

Usher综合征是一种遗传性疾病，会导致听力损失（HL）和色素性视网膜炎（RP）。三种主要的临床类型，即I，II和II类型的Usher综合征，以听力损失的严重程度以及存在或不存在前庭功能障碍来区分。 I型患者患有严重的听力损失，RP和前庭功能障碍。 I型患者患有严重的听力损失，RP和前庭功能障碍。 III型与I型和II型可以通过渐进的HL和可变的前庭缺陷区分开。现在，至少十个不同的遗传基因座被认为与乌瑟综合征的三种临床类型有关。我们已经收集了世界上最大的Usher家庭系列，这是一种适合该项目提出的研究的独特资源。我们建议通过测试与所有Usher基因座存在有关的假设以及估计每个综合症的相对贡献对Usher综合征的整体频率的相对贡献，以阐明异质性问题。此外，我们建议确定MyO7A和USH2A中突变的分布，以识别和表征引起IIB，IA，ID/F，IE和III的usher类型的基因，并为USHER II型C和任何其他新的USHER基因定位。由于Usher综合征会导致两种最重要的人类感官的失去，因此这种疾病患者的负担是巨大的。它的作用是将他们与社会的其他成员隔离开来，并降低了他们独立行动的能力。近15,000人中有近1个人患有Usher综合征。 Usher亚型诊断障碍的能力将得到增强，从而导致更准确的遗传咨询。更好地理解对乌瑟综合征的潜在病因是朝着有效治疗发展的关键第一步。 Usher综合征提供了一种研究两种主要感官如何相关的方法，并对有关Usher综合征病因的问题的答案将揭示有关正常视网膜和听觉功能常见的发育，代谢和/或监管途径的重要和新颖信息。