Votruba M, Moore A T, Bhattacharya S S
Department of Molecular Genetics, Institute of Ophthalmology, University College London, UK.
J Med Genet. 1998 Oct;35(10):793-800. doi: 10.1136/jmg.35.10.793.
Inherited optic neuropathies are a significant cause of childhood and adult blindness and dominant optic atrophy (DOA) is the most common form of autosomally inherited (non-glaucomatous) optic neuropathy. Patients with DOA present with an insidious onset of bilateral visual loss and they characteristically have temporal optic nerve pallor, centrocaecal visual field scotoma, and a colour vision deficit, which is frequently blue-yellow. Evidence from histological and electrophysiological studies suggests that the pathology is confined to the retinal ganglion cell. A gene for dominant optic atrophy (OPA1) has been mapped to chromosome 3q28-qter, and studies are under way to refine the genetic interval in which the gene lies, to map the region physically, and hence to clone the gene. A second locus for dominant optic atrophy has recently been shown to map to chromosome 18q12.2-12.3 near the Kidd blood group locus. The cloning of genes for dominant optic atrophy will provide important insights into the pathophysiology of the retinal ganglion cell in health and disease. These insights may prove to be of great value in the understanding of other primary ganglion cell diseases, such as the mitochondrially inherited Leber's hereditary optic neuropathy and other diseases associated with ganglion cell loss, such as glaucoma.
遗传性视神经病变是儿童和成人失明的一个重要原因，显性遗传性视神经萎缩（DOA）是常染色体显性遗传（非青光眼性）视神经病变最常见的形式。DOA患者表现为隐匿性双侧视力丧失，其特征性表现为颞侧视神经苍白、中心暗点视野缺损以及色觉缺陷，后者常为蓝黄色。组织学和电生理学研究证据表明，病变局限于视网膜神经节细胞。显性遗传性视神经萎缩基因（OPA1）已被定位于3号染色体长臂28区至末端，目前正在进行研究以精确确定该基因所在的遗传区间，对该区域进行物理定位，从而克隆该基因。最近已证明显性遗传性视神经萎缩的另一个基因座定位于18号染色体长臂12.2区至12.3区，靠近基德血型位点。克隆显性遗传性视神经萎缩基因将为深入了解视网膜神经节细胞在健康和疾病状态下的病理生理学提供重要线索。这些线索可能在理解其他原发性神经节细胞疾病（如线粒体遗传的Leber遗传性视神经病变）以及与神经节细胞丢失相关的其他疾病（如青光眼）方面具有重要价值。
