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

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.

KEYWORDS:

• Gyrate Atrophy
• vitreous hemorrhage
• chorioretinal degeneration
• autosomal recessive
• Sanger sequencing

Acknowledgments

We thank the patient and family members for giving consent to participation in this study.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This work was supported by the Department of Biotechnology, Ministry of Science and Technology, India [BT/NNT/28/SP18830/2018].