ABSTRACT

Background: Gyrate Atrophy (GA) is a rare autosomal recessive disorder characterized by progressive chorioretinal degeneration. It is caused due to mutations in OAT gene that encodes a defective ornithine-δ-aminotransferase enzyme. We aim to identify the molecular cause of the disease and correlate it with the phenotype.

Materials and Methods: Clinical, biochemical and genetic analyses were performed in siblings with GA.

Case Description: A 10-year-old girl presented with impaired vision was clinically diagnosed to have peripheral chorioretinal degeneration in both eyes due to GA with vitreous hemorrhage in the right eye. Similar chorioretinal degeneration was observed in the patient’s sibling, while parents were normal. Biochemical analysis of plasma by LC-MS/MS showed an elevated ornithine level of 892.8 µmol/L in the patient and 572.3 µmol/L in the sibling. Familial genetic screening by Sanger sequencing revealed a nonsense mutation in exon 11 of the OAT gene (c.1192C>T; p.Arg398Ter) in all the family members with a homozygous mutation in the patient and sibling, and heterozygous mutation in the parents. The patient was under follow-up with an arginine-restricted diet. At the last follow-up, the vitreous hemorrhage of right eye had resolved with an improvement in visual acuity and left eye remained stable with 6/12.

Conclusion: Our patient is a rare case of gyrate atrophy presented with vitreous hemorrhage and nonsense OAT gene mutation, inherited in the autosomal recessive pattern. This report highlights the phenotypic variability among the siblings with the same mutation in OAT gene for the first time.

摘要

背景：旋转萎缩 (GA) 是一种罕见的常染色体隐性遗传疾病，其特征是进行性脉络膜视网膜变性。它是由编码有缺陷的鸟氨酸-δ-氨基转移酶的OAT基因突变引起的。我们的目标是确定疾病的分子原因并将其与表型相关联。

材料和方法：对患有 GA 的兄弟姐妹进行临床、生化和遗传分析。

病例描述： 10 岁女孩视力受损，临床诊断为 GA 导致双眼周围脉络膜视网膜变性，右眼玻璃体积血。在患者的兄弟姐妹中观察到类似的脉络膜视网膜变性，而父母则正常。通过 LC-MS/MS 对血浆的生化分析显示，患者的鸟氨酸水平升高 892.8 µmol/L，兄弟姐妹的鸟氨酸水平升高 572.3 µmol/L。通过 Sanger 测序进行的家族遗传筛查揭示了OAT外显子 11 的无义突变基因 (c.1192C>T; p.Arg398Ter) 在患者和兄弟姐妹中具有纯合突变，在父母中具有杂合突变的所有家庭成员中。该患者正在接受精氨酸限制饮食的随访。末次随访时，右眼玻璃体积血消退，视力提高，左眼稳定，6/12。

结论：我们的患者是一例罕见的旋转萎缩病例，表现为玻璃体出血和无意义的OAT基因突变，常染色体隐性遗传。该报告首次强调了具有相同OAT基因突变的兄弟姐妹之间的表型变异性。