Institute of Ophthalmology, University College London, London, United Kingdom.
Ophthalmology. 2012 Mar;119(3):596-605. doi: 10.1016/j.ophtha.2011.09.017. Epub 2011 Dec 17.
To describe phenotypic variability and to report novel mutational data in patients with gyrate atrophy.
Retrospective case series.
Seven unrelated patients (10 to 52 years of age) with clinical and biochemical evidence of gyrate atrophy.
Detailed ophthalmologic examination, fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain optical coherence tomography, and microperimetry testing were performed. The coding region and intron-exon boundaries of ornithine aminotransferase (OAT) were analyzed. OAT mRNA was isolated from peripheral blood leucocytes of 1 patient and analyzed.
OAT mutation status and resultant clinical, structural, and functional characteristics.
Funduscopy revealed circular areas of chorioretinal atrophy, and FAF imaging showed sharply demarcated areas of increased or preserved signal in all 7 patients. Spectral-domain optical coherence tomography revealed multiple intraretinal cystic spaces and hyperreflective deposit in the ganglion cell layer of all study subjects. Round tubular, rosette-like structures located in the outer nuclear layer of the retinae of the 4 older patients were observed (termed outer retinal tubulation). Thickening was evident in the foveolae of younger patients, despite the posterior pole appearing relatively preserved. Macular function, assessed by microperimetry, was preserved over areas of normal or increased autofluorescence. However, sensitivity was reduced even in structurally intact parts of the retina. The molecular pathologic features were determined in all study subjects: 9 mutations, 4 novel, were detected in the OAT gene. OAT mRNA was isolated from blood leukocytes, and monoallelic expression of a mutated allele was demonstrated in 1 patient.
Fundus autofluorescence imaging can reveal the extent of neurosensory dysfunction in gyrate atrophy patients. Macular edema is a uniform finding; the fovea is relatively thick in early stages of disease and retinal tubulation is present in advanced disease. Analysis of leukocyte RNA complements the high sensitivity of conventional sequencing of genomic DNA for mutation detection in this gene.
描述鸟氨酸转氨酶（OAT）缺乏症的表型变异性并报告新的突变数据。
回顾性病例系列研究。
7 名（年龄 10 至 52 岁）无关联的 OAT 缺乏症患者，均具有临床和生化证据。
详细的眼科检查、眼底照相、眼底自发荧光（FAF）成像、频域光学相干断层扫描（OCT）和微视野检查。分析 OAT 的编码区和内含子-外显子边界。从 1 名患者的外周血白细胞中分离 OAT mRNA 并进行分析。
OAT 突变状态及相应的临床、结构和功能特征。
眼底检查发现脉络膜视网膜萎缩的圆形区域，FAF 成像显示 7 名患者的信号均有明显边界的增加或保留区。频域 OCT 显示所有研究对象的视网膜内均有多个视网膜内囊腔和神经节细胞层的高反射性沉积物。在 4 名年龄较大的患者的视网膜外核层中观察到圆形管状、玫瑰花结样结构（称为外视网膜管化）。尽管后极相对保留，但年轻患者的中央凹明显增厚。微视野评估的黄斑功能在正常或增加自发荧光的区域保留，但即使在视网膜结构完整的部位，敏感性也降低。在所有研究对象中确定了分子病理学特征：在 OAT 基因中检测到 9 个突变，其中 4 个是新的。从血液白细胞中分离 OAT mRNA，并在 1 名患者中证实单等位基因表达突变等位基因。
FAF 成像可以揭示鸟氨酸转氨酶缺乏症患者的神经感觉功能障碍的程度。黄斑水肿是一种普遍的发现；在疾病的早期，中央凹相对较厚，并且在晚期存在视网膜管化。白细胞 RNA 的分析补充了常规基因组 DNA 测序检测该基因突变的高灵敏度。
