Department of Vitreo-retinal Services, Aravind Eye Hospital and Post Graduate Institute of Ophthalmology, Madurai, India.
Department of Molecular Genetics, Aravind Medical Research Foundation, Madurai, India.
Ophthalmic Genet. 2021 Jun;42(3):300-303. doi: 10.1080/13816810.2020.1870149. Epub 2021 Jan 19.
Gyrate Atrophy (GA) is a rare autosomal recessive disorder characterized by progressive chorioretinal degeneration. It is caused due to mutations in 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. Clinical, biochemical and genetic analyses were performed in siblings with GA. 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 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. Our patient is a rare case of gyrate atrophy presented with vitreous hemorrhage and nonsense gene mutation, inherited in the autosomal recessive pattern. This report highlights the phenotypic variability among the siblings with the same mutation in gene for the first time.
鸟氨酸氨甲酰基转移酶缺乏症（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。该病是由于编码缺陷的鸟氨酸δ-氨基转移酶的基因突变引起的。我们旨在确定该疾病的分子病因，并将其与表型相关联。对 GA 患者的兄弟姐妹进行了临床、生化和遗传分析。一名 10 岁女孩因视力受损就诊，临床诊断为双眼周边脉络膜视网膜变性（GA），右眼伴有玻璃体积血。患者的兄弟姐妹也观察到类似的脉络膜视网膜变性，而父母正常。通过 LC-MS/MS 对血浆进行生化分析显示，患者的鸟氨酸水平升高至 892.8μmol/L，患者的兄弟姐妹为 572.3μmol/L。对患者及其兄弟姐妹的 Sanger 测序显示， 基因第 11 外显子的无义突变（c.1192C>T;p.Arg398Ter）在所有家庭成员中均存在，患者和兄弟姐妹为纯合突变，父母为杂合突变。该患者接受了限制精氨酸饮食的随访。最后一次随访时，右眼玻璃体积血已吸收，视力有所改善，左眼保持稳定，视力为 6/12。我们的患者是一例罕见的 GA 病例，表现为玻璃体积血和无意义的 基因突变，呈常染色体隐性遗传模式。该报告首次强调了具有相同 基因突变的兄弟姐妹之间表型的可变性。
