Retinal Structure, Function, and Molecular Pathologic Features in Gyrate Atrophy

• Published in: Ophthalmology (Rochester, Minn.) Vol. 119; no. 3; pp. 596 - 605
• Main Authors: Sergouniotis, Panagiotis I., Davidson, Alice E., Lenassi, Eva, Devery, Sophie R., Moore, Anthony T., Webster, Andrew R.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.2012; Elsevier
• Subjects: Adolescent; Adult; Biological and medical sciences; Child; Computational Biology; Contrast Sensitivity - physiology; DNA Mutational Analysis; Female; Fluorescein Angiography; Gyrate Atrophy - enzymology; Gyrate Atrophy - genetics; Gyrate Atrophy - physiopathology; Humans; Male; Medical sciences; Middle Aged; Miscellaneous; Mutation, Missense; Ophthalmology; Ophthalmoscopy; Ornithine-Oxo-Acid Transaminase - blood; Ornithine-Oxo-Acid Transaminase - genetics; Phenotype; Retina - enzymology; Retina - physiopathology; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Tomography, Optical Coherence; Visual Acuity - physiology; Visual Field Tests; Visual Fields; Atrophy; Retina; Ophthalmology; Structure
• ISSN: 0161-6420; 1549-4713; 1549-4713
• DOI: 10.1016/j.ophtha.2011.09.017

To describe phenotypic variability and to report novel mutational data in patients with gyrate atrophy. Retrospective case series. Seven unrelated patients (10 to 52 years of age) with clinical and biochemical evidence of gyrate atrophy. Detailed ophthalmologic examination, fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain optical coherence tomography, and microperimetry testing were performed. The coding region and intron–exon boundaries of ornithine aminotransferase (OAT) were analyzed. OAT mRNA was isolated from peripheral blood leucocytes of 1 patient and analyzed. OAT mutation status and resultant clinical, structural, and functional characteristics. Funduscopy revealed circular areas of chorioretinal atrophy, and FAF imaging showed sharply demarcated areas of increased or preserved signal in all 7 patients. Spectral-domain optical coherence tomography revealed multiple intraretinal cystic spaces and hyperreflective deposit in the ganglion cell layer of all study subjects. Round tubular, rosette-like structures located in the outer nuclear layer of the retinae of the 4 older patients were observed (termed outer retinal tubulation). Thickening was evident in the foveolae of younger patients, despite the posterior pole appearing relatively preserved. Macular function, assessed by microperimetry, was preserved over areas of normal or increased autofluorescence. However, sensitivity was reduced even in structurally intact parts of the retina. The molecular pathologic features were determined in all study subjects: 9 mutations, 4 novel, were detected in the OAT gene. OAT mRNA was isolated from blood leukocytes, and monoallelic expression of a mutated allele was demonstrated in 1 patient. Fundus autofluorescence imaging can reveal the extent of neurosensory dysfunction in gyrate atrophy patients. Macular edema is a uniform finding; the fovea is relatively thick in early stages of disease and retinal tubulation is present in advanced disease. Analysis of leukocyte RNA complements the high sensitivity of conventional sequencing of genomic DNA for mutation detection in this gene. The author(s) have no proprietary or commercial interest in any materials discussed in this article.