Autosomal Dominant Retinal Dystrophy With Electronegative Waveform Associated With a Novel RAX2 Mutation.
Autosomal Dominant Retinal Dystrophy With Electronegative Waveform Associated With a Novel RAX2 Mutation.
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DOI：
10.1001/jamaophthalmol.2015.0357
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发表时间：
2015-06
影响因子：
8.1
通讯作者：
Pennesi ME
中科院分区：
文献类型：
--
作者：
Yang P;Chiang PW;Weleber RG;Pennesi ME
据我们所知，在这项研究中评估的患者代表了第一个完整的临床描述，该家庭具有常染色体显性遗传模式，视网膜营养不良与RAX2的新突变相关。临床评估4名患者和5名未受影响的家庭成员，描述疾病随时间的表型，并确定相关的基因突变。一项前瞻性、纵向、观察性、病例系列分析，研究对象是波特兰俄勒冈健康与科学大学Casey眼科研究所一个受影响家庭的9名成员。研究时间为1992年7月31日至2014年8月11日。临床评估包括眼科检查、眼底彩色摄影、自身荧光成像、光谱域光学相干断层扫描、动态视野测试和视网膜电图。采用下一代测序进行基因突变筛选，并通过Sanger测序确认鉴定出的突变。视网膜营养不良的临床诊断和纵向特征及基因突变的鉴定。该家庭的6名成员被确定患有视网膜营养不良（4人接受了检查，3人接受了基因测试）。对5名未受影响的家庭成员进行临床评估（2名进行基因检测）。视网膜营养不良的发病年龄是可变的。所有患者均表现为视力下降、中心暗斑、蜡样椎间盘苍白、脉管系统减弱、黄斑小黄斑沉积和/或黄斑色素斑驳，视网膜电图异常，显示混合性视锥和视杆功能障碍以及对明亮闪光的暗位电负性反应。在任何受影响的患者中，没有发现其他导致视网膜电图电负性的原因。基因检测显示，据我们所知，在视网膜营养不良患者中RAX2发生了一种新的移码杂合突变。以常染色体显性方式遗传的RAX2移码杂合突变与混合锥和杆功能障碍有关。在患者中，发病年龄和光感受器功能障碍的具体模式存在差异，但临床病程缓慢进展。筛选RAX2突变对有暗位电负性闪光反应的患者及其家庭具有预后价值。
The patients evaluated in this study, to our knowledge, represent the first complete clinical description of a family with an autosomal dominant inheritance pattern of retinal dystrophy associated with a novel mutation in RAX2. To clinically evaluate 4 patients and 5 unaffected family members, characterize the disease phenotype over time, and identify the associated genetic mutation. A prospective, longitudinal, observational, case-series analysis of 9 members of an affected family at the Casey Eye Institute, Oregon Health and Science University, Portland. The dates of the study were from July 31, 1992, to August 11, 2014. Clinical evaluations included eye examination, color fundus photography, autofluorescence imaging, spectral-domain optical coherence tomography, kinetic visual field testing, and electroretinography. Genetic mutation screening was performed with next-generation sequencing, and identified mutations were confirmed with Sanger sequencing. Clinical diagnosis and longitudinal characterization of retinal dystrophy and identification of genetic mutation. Six members of the family were identified as having retinal dystrophy (4 were examined, and 3 were genetically tested). Five unaffected family members were clinically evaluated (2 were genetically tested). The age at onset of retinal dystrophy was variable. All affected individuals presented with declining visual acuity, central scotomas, waxy disc pallor, attenuated vasculature, small yellow macular deposits and/or macular pigment mottling, and abnormal electroretinograms demonstrating mixed cone and rod dysfunction and a scotopic electronegative response to bright flashes. There were no other causes of an electronegative electroretinogram identified in any of the affected patients. Genetic testing revealed, to our knowledge, a novel frameshift heterozygous mutation in RAX2 in the patients with retinal dystrophy. A frameshift heterozygous mutation in RAX2 inherited in an autosomal dominant fashion was associated with mixed cone and rod dysfunction. Among the patients, there was variability in the age at onset and in the specific pattern of photoreceptor dysfunction, but the clinical course was nevertheless slowly progressive. Screening for RAX2 mutation could provide prognostic value for patients and families with scotopic electronegative responses to bright flashes.
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影响因子：
1.4
作者：
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通讯作者：
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