Katz Bradley J, Zhao Yu, Warner Judith E A, Tong Zongzhong, Yang Zhenglin, Zhang Kang
Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
Am J Med Genet A. 2006 Oct 15;140(20):2207-11. doi: 10.1002/ajmg.a.31455.
Autosomal dominant optic atrophy (ADOA) is the most common inherited optic atrophy. Clinical features of ADOA include a slowly progressive bilateral loss of visual acuity, constriction of peripheral visual fields, central scotomas, and color vision abnormalities. Although ADOA is the most commonly inherited optic atrophy, autosomal recessive, X-linked, mitochondrial, and sporadic forms have also been reported. Four families with X-linked optic atrophy (XLOA) were previously described. One family was subsequently linked to Xp11.4-Xp11.2 (OPA2). This investigation studied one multi-generation family with an apparently X-linked form of optic atrophy and compared their clinical characteristics with those of the previously described families, and determined whether this family was linked to the same genetic locus. Fifteen individuals in a three-generation Idaho family underwent complete eye examination, color vision testing, automated perimetry, and fundus photography. Polymorphic markers were used to genotype each individual and to determine linkage. Visual acuities ranged from 20/30 to 20/100. All affected subjects had significant optic nerve pallor. Obligate female carriers were clinically unaffected. Preliminary linkage analysis (LOD score = 1.8) revealed that the disease gene localized to the OPA2 locus on Xp11.4-Xp11.2. Four forms of inherited optic neuropathy, ADOA, autosomal recessive optic atrophy (Costeff Syndrome), Leber hereditary optic neuropathy, and Charcot-Marie-Tooth disease with optic atrophy, are associated with mitochondrial dysfunction. Future identification of the XLOA gene will reveal whether this form of optic atrophy is also associated with a mitochondrial defect. Identification of the XLOA gene will advance our understanding of the inherited optic neuropathies and perhaps suggest treatments for these diseases. An improved understanding of inherited optic neuropathies may in turn advance our understanding of acquired optic nerve diseases, such as glaucoma and ischemic optic neuropathy.
常染色体显性遗传性视神经萎缩（ADOA）是最常见的遗传性视神经萎缩。ADOA的临床特征包括视力缓慢进行性双侧丧失、周边视野缩窄、中心暗点和色觉异常。尽管ADOA是最常见的遗传性视神经萎缩，但常染色体隐性、X连锁、线粒体和散发性形式也有报道。先前已描述了四个患有X连锁视神经萎缩（XLOA）的家系。随后一个家系被定位到Xp11.4 - Xp11.2（OPA2）。本研究调查了一个具有明显X连锁形式视神经萎缩的多代家系，并将其临床特征与先前描述的家系进行比较，以确定该家系是否与相同的基因位点连锁。爱达荷州一个三代家系中的15名个体接受了全面的眼部检查、色觉测试、自动视野检查和眼底摄影。使用多态性标记对每个个体进行基因分型并确定连锁关系。视力范围为20/30至20/100。所有受影响的受试者均有明显的视神经苍白。必然的女性携带者在临床上未受影响。初步连锁分析（LOD分数 = 1.8）表明，疾病基因定位于Xp11.4 - Xp11.2上的OPA2位点。四种遗传性视神经病变形式，即ADOA、常染色体隐性遗传性视神经萎缩（科斯特夫综合征）、Leber遗传性视神经病变以及伴有视神经萎缩的夏科 - 马里 - 图斯病，都与线粒体功能障碍有关。未来对XLOA基因的鉴定将揭示这种形式的视神经萎缩是否也与线粒体缺陷有关。XLOA基因的鉴定将增进我们对遗传性视神经病变的理解，并可能为这些疾病提供治疗建议。对遗传性视神经病变理解的改善反过来可能增进我们对获得性视神经疾病，如青光眼和缺血性视神经病变的理解。
