An evaluation of genetic causes and environmental risks for bilateral optic atrophy

• Published in: PloS one Vol. 14; no. 11; p. e0225656
• Main Authors: Chen, Andrew T, Brady, Lauren, Bulman, Dennis E, Sundaram, Arun N E, Rodriguez, Amadeo R, Margolin, Edward, Waye, John S, Tarnopolsky, Mark A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.11.2019; Public Library of Science (PLoS)
• Subjects: Aconitate Hydratase - genetics; Alcohol; Alcohol Drinking; Atrophy; Biology and Life Sciences; Comparative analysis; Deoxyribonucleic acid; DNA; DNA sequencing; DNA, Mitochondrial - chemistry; DNA, Mitochondrial - genetics; DNA, Mitochondrial - metabolism; Environmental Exposure; Environmental risk; Environmental toxicology; Ethanol; Evaluation; Gene sequencing; Genes; Genetic diversity; Genetic research; Genetic screening; Genetic testing; Genetic variance; Genetic Variation; Genetics; GTP Phosphohydrolases - genetics; Health care facilities; High-Throughput Nucleotide Sequencing; Humans; Medical centers; Medicine and Health Sciences; Membrane Proteins - genetics; Mitochondrial DNA; Mutation; Next-generation sequencing; Optic atrophy; Optic Atrophy - genetics; Optic Atrophy - pathology; Optic nerve; Patients; Pediatrics; Phosphorylation; Physical Sciences; Retrospective Studies; Risk analysis; Risk Factors; Rodriguez, Edward; Sequence Analysis, DNA; Smoke; Smoking; Social Sciences; Vibration; Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0225656

To assess the clinical utility of next-generation sequencing (NGS) for the diagnosis of patients with optic atrophy (OA). Retrospective cohort study. 97 patients were referred to the McMaster University Medical Center (Hamilton, Ontario) for evaluation of bilateral OA. All patients were sent for NGS including a 22 nuclear gene panel and/or complete mitochondrial DNA (mtDNA) sequencing. Positive genetic test results and abnormal vibration sensation were compared in patients +/- environmental exposures or a family history. 19/94 (20.2%) had a positive nuclear variant, of which 15/19 (78.9%) were in the OPA1 gene. No positive mtDNA variants were identified. The detection of a positive genetic variant was significantly different in patients who reported excessive ethanol use, but not in patients who smoke (0/19 (0%) vs. 19/78 (24.4%), P = 0.0164 and 4/22 (18.2%) vs. 15/74 (20.3%), P = 0.829, respectively). Patients with a positive family history were more likely to have a positive genetic variant compared to patients with a negative family history (P = 0.0112). There were significantly more excessive drinkers with an abnormal vibration sensation (P = 0.026), and with a similar trend in smokers (P = 0.074). All positive genetic variants were identified in nuclear genes. We identified a potential independent pathophysiological link between a history of excessive ethanol consumption and bilateral OA. Further investigations should evaluate and identify potential environmental risk factors for OA.