Moumoulidis I, Axon P, Baguley D, Reid E
Department of Otolaryngology, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, UK.
Clin Otolaryngol. 2007 Aug;32(4):239-47. doi: 10.1111/j.1365-2273.2007.01475.x.
The aetiology of otosclerosis is not fully understood despite intensive research. It is, however, certain that a genetic component plays a significant role in the manifestation of otosclerosis, although the precise mode of inheritance is still uncertain.
To provide an up-to-date review for the genetics of otosclerosis. The mode of inheritance, chromosomal and linkage studies are presented. In addition, the possible genetic relationship between otosclerosis and osteogenesis imperfecta, and the association between otosclerosis and specific human leucocyte antigen types are described.
Systematic analysis of the literature was focused on any information related to the genetics of otosclerosis.
A MEDLINE search (1960-2007) was undertaken to perform a comprehensive review. Articles were also identified through searches of the files of authors.
The majority of epidemiological studies on families with otosclerosis suggest an autosomal dominant mode of inheritance with reduced penetrance of approximately 40%. Genetic linkage studies have demonstrated the presence of six loci (OTSC1, OTSC2, OTSC3, OTSC4, OTSC5 and OTSC7) located on chromosomes 15q, 7q, 6p, 16q, 3q and 6q respectively. Although these loci have been mapped, no causative genes have been identified, and we have little idea of the molecular process involved in this disease. While clinical similarities and some unreplicated genetic association studies suggest an aetiological relationship between otosclerosis and osteogenesis imperfecta-type I, there is no definite evidence of a common pathological process between the two diseases.
Otosclerosis may be considered as a complex disease with relatively common monogenic forms. Knowledge of these genes could lead to substantial improvements in our ability to diagnose and possibly even prevent or treat this type of hearing deterioration.
尽管进行了深入研究，但耳硬化症的病因仍未完全明确。不过可以确定的是，遗传因素在耳硬化症的表现中起着重要作用，尽管确切的遗传模式仍不确定。
对耳硬化症的遗传学进行最新综述。介绍其遗传模式、染色体及连锁研究。此外，还描述了耳硬化症与成骨不全之间可能的遗传关系，以及耳硬化症与特定人类白细胞抗原类型之间的关联。
对文献进行系统分析，重点关注与耳硬化症遗传学相关的任何信息。
进行了MEDLINE检索（1960 - 2007年）以进行全面综述。还通过搜索作者的文件来识别文章。
大多数针对耳硬化症家族的流行病学研究表明其遗传模式为常染色体显性遗传，外显率约为40%，有所降低。遗传连锁研究已证明分别位于15号染色体长臂、7号染色体长臂、6号染色体短臂、16号染色体长臂、3号染色体长臂和6号染色体短臂上存在六个基因座（OTSC1、OTSC2、OTSC3、OTSC4、OTSC5和OTSC7）。尽管这些基因座已被定位，但尚未确定致病基因，而且我们对该疾病所涉及的分子过程知之甚少。虽然临床相似性和一些未重复的遗传关联研究表明耳硬化症与I型成骨不全之间存在病因学关系，但尚无确凿证据表明这两种疾病之间存在共同的病理过程。
耳硬化症可被视为一种具有相对常见单基因形式的复杂疾病。了解这些基因可能会极大地提高我们诊断甚至预防或治疗这种听力减退类型的能力。
