Fischel-Ghodsian N
Ahmanson Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Hum Mutat. 1999;13(4):261-70. doi: 10.1002/(SICI)1098-1004(1999)13:4<261::AID-HUMU1>3.0.CO;2-W.
The first molecular defect for nonsyndromic hearing loss was identified in 1993, and was a mitochondrial mutation. Since then a number of inherited mitochondrial DNA (mtDNA) mutations have been implicated in hearing loss, and acquired mtDNA mutations have been proposed as one of the causes of the hearing loss associated with aging, presbyacusis. These molecular findings have raised as many questions as they have answered, however, since the pathophysiology between the mutations and the clinical phenotype remains poorly understood. This mini-review will, after a short background review of mitochondrial genetics, (1) outline the different mtDNA mutations associated with inherited syndromic, nonsyndromic, and ototoxic hearing loss, (2) summarize the data on acquired mtDNA mutations and their possible association with presbyacusis, (3) describe the biochemical consequences of the inherited mtDNA mutations, (4) suggest the clinical implications of the identification of these mutations, and (5) discuss the penetrance and tissue specificity of the hearing associated mtDNA mutations.
1993年，非综合征性听力损失的首个分子缺陷被确定，是一种线粒体突变。从那时起，许多遗传性线粒体DNA（mtDNA）突变被认为与听力损失有关，并且获得性mtDNA突变被认为是与衰老相关的听力损失（老年性聋）的病因之一。然而，这些分子研究结果带来的问题和给出的答案一样多，因为突变与临床表型之间的病理生理学仍知之甚少。本综述将在对线粒体遗传学进行简短的背景回顾之后，（1）概述与遗传性综合征性、非综合征性和耳毒性听力损失相关的不同mtDNA突变，（2）总结关于获得性mtDNA突变及其与老年性聋可能关联的数据，（3）描述遗传性mtDNA突变的生化后果，（4）提出鉴定这些突变的临床意义，以及（5）讨论与听力相关的mtDNA突变的外显率和组织特异性。
