ABSTRACT

Background: Gyrate atrophy of the choroid and retina (GA) is a rare autosomal recessive disorder characterized by nyctalopia, myopia, sharply demarcated expanding peripheral chorioretinal atrophic lesions, early cataract, progressive visual loss and hyperornithinemia. Only three cases of GA associated with rhegmatogenous retinal detachments (RRD) have been reported. The genotype-phenotype correlation of RRD in GA is limited by lack of genetic information in the previously reported cases. Here we report two young sisters with a characteristic GA phenotype associated with a novel variant in the ornithine aminotransferase gene (OAT), in whom one developed unilateral RRD at the age of 9 years.

Materials and Methods: Retrospective report of two cases including genetic analysis and multimodal retinal imaging.

Results: A 9-year-old Saudi girl presented with a funnel-shaped RRD, extensive proliferative vitreoretinopathy, peripheral choroidal detachment and neovascular glaucoma in her right eye. Fundus examination of her left eye showed an attached retina with sharply-demarcated peripheral chorioretinal atrophic patches suggestive of GA. Whole exome sequencing confirmed GA by revealing a homozygous c.980 C > G (p. Pro327Arg) variant in exon 8 of OAT. The RRD was inoperable. The chorioretinal lesions in the left eye enlarged slowly over 3 years of follow up. Examination of the proband’s older sister revealed a similar but more advanced GA phenotype in both eyes.

Conclusions: A characteristic GA phenotype associated with a novel variant in OAT is reported. This variant might be associated with childhood-onset RRD in the proband.

摘要

背景：脉络膜和视网膜旋转萎缩 (GA) 是一种罕见的常染色体隐性遗传疾病，其特征是夜视、近视、边界清晰的扩张型周边脉络膜视网膜萎缩性病变、早期白内障、进行性视力丧失和高鸟氨酸血症。仅报道了 3 例与孔源性视网膜脱离 (RRD) 相关的 GA 病例。GA 中 RRD 的基因型-表型相关性受到先前报道病例中缺乏遗传信息的限制。在这里，我们报告了两个具有特征性 GA 表型的年轻姐妹，其与鸟氨酸转氨酶基因(OAT ) 的一种新变异相关，其中一个在 9 岁时患上了单侧 RRD。

材料和方法：包括遗传分析和多模态视网膜成像在内的两个病例的回顾性报告。

结果：一名 9 岁沙特女孩右眼出现漏斗状 RRD、广泛增殖性玻璃体视网膜病变、周围脉络膜脱离和新生血管性青光眼。她的左眼眼底检查显示附着的视网膜有边界清晰的周边脉络膜视网膜萎缩斑块，提示 GA。全外显子测序通过揭示OAT外显子 8 中的纯合 c.980 C > G (p. Pro327Arg) 变体证实了 GA 。RRD 无法运行。左眼脉络膜视网膜病变在 3 年的随访中缓慢扩大。对先证者姐姐的检查显示双眼有相似但更高级的 GA 表型。

结论：报告了与OAT 中的新变体相关的特征性 GA 表型。这种变异可能与先证者儿童期发病的 RRD 相关。