Otosclerosis-A Molecular Genetic Study

描述（由申请人提供）：在白色成年人中，耳硬化症是 听力障碍的最常见原因。 这种疾病是由耳囊的骨稳态异常引起的， 这通常会导致传导性听力损失， 镫骨底板，虽然也可能发生感音神经性听力损失。的 耳硬化症的病因不明，遗传和环境因素 被牵连了虽然耳硬化症的遗传学是有争议的， 大多数研究表明常染色体显性遗传， 外显率利用两个显示这种孟德尔遗传的大家族 模式，我们已经定位了两个耳硬化症引起的基因，OTSCI和OTSC 2。 我们还表明，至少有一个额外的位点，OTSC 3，存在。 在这一初步工作的基础上，我们建议： 1)克隆OTSCI和OTSC 2基因; 2)应用连锁分析鉴定耳硬化症新基因位点 3)通过连锁和连锁不平衡鉴定新的耳硬化症基因座 对希腊家庭的分析; 4)使用非参数连锁分析鉴定新的耳硬化症位点 受影响的同胞对。

DESCRIPTION (provided by applicant): Among white adults, otosclerosis is the single most common cause of hearing impairment. The disease is caused by abnormal bone homeostasis of the otic capsule, which usually results in a conductive hearing loss due to fixation of the stapes footplate, although sensorineural hearing loss also may occur. The etiology of otosclerosis is unknown, and both genetic and environmental factors have been implicated. Although the genetics of otosclerosis are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. Using two large families showing this type of Mendelian inheritance pattern, we have localized two otosclerosis-causing genes, OTSCI and OTSC2. We also have shown that at least one additional locus, OTSC3, exists. Continuing on this initial body of work, we propose to: 1) Clone the OTSCI and OTSC2 genes; 2) Identify novel otosclerosis loci by linkage analysis; 3) Identify novel otosclerosis loci by linkage and linkage disequilibrium analyses in families from Greece; 4) Identify novel otosclerosis loci by non-parametric linkage analysis using affected sib pairs.