Variable phenotypes of gyrate atrophy in siblings with a nonsense mutation in OAT gene

• Published in: Ophthalmic genetics 2021-06, Vol.42 (3), p.300-303
• Main Authors: Sen, Sagnik, Kannan, Saraswathi Karuvel, Shanmugam, Ulaganathan, Rajan, Renu, Babu, Naresh, Vanniarajan, Ayyasamy
• Format: Article
• Language: English
• Subjects: Adolescent; Child; Chromatography, Liquid; Codon, Nonsense - genetics; Female; Fluorescein Angiography; Gyrate Atrophy - diagnosis; Gyrate Atrophy - diet therapy; Gyrate Atrophy - genetics; Humans; Ornithine-Oxo-Acid Transaminase - blood; Ornithine-Oxo-Acid Transaminase - genetics; Pedigree; Phenotype; Siblings; Tandem Mass Spectrometry; Visual Acuity - physiology; Vitreous Hemorrhage - diagnosis; Vitreous Hemorrhage - physiopathology
• ISSN: 1381-6810; 1744-5094
• DOI: 10.1080/13816810.2020.1870149

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.