Otosclerosis-A Molecular Genetic Study

描述(申请人提供)：在白人成年人中，耳硬化症是 听力受损的单一最常见原因。 这种疾病是由耳囊的骨平衡异常引起的， 这通常导致传导性听力损失，因为固定 尽管也可能发生感音神经性听力损失，但也可发生踝骨足底板损伤。这个 耳硬化症的病因不明，既有遗传因素，也有环境因素。 都有牵连。尽管耳硬化症的遗传学存在争议， 大多数研究表明常染色体显性遗传与减少 洞察力。使用两个显示孟德尔式遗传类型的大家族 模式，我们已经定位了两个导致耳硬化症的基因，OTSCI和OTSC2。 我们还证明了至少有一个额外的基因座OTSC3存在。 在这项初步工作的基础上，我们建议： 1)克隆OTSCI和OTSC2基因； 2)通过连锁分析确定新的耳硬化症基因座； 3)利用连锁和连锁不平衡识别新的耳硬化症基因座 对来自希腊的家庭的分析； 4)用非参数连锁分析方法识别新的耳硬化症基因座 受影响的兄弟姐妹对。

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.