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

Autoři: Andrew T. Chen aff001;  Lauren Brady aff001;  Dennis E. Bulman aff002;  Arun N. E. Sundaram aff003;  Amadeo R. Rodriguez aff004;  Edward Margolin aff005;  John S. Waye aff006;  Mark A. Tarnopolsky aff001
Působiště autorů: Department of Pediatrics, McMaster University, Hamilton, ON, Canada aff001;  Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada aff002;  Department of Ophthalmology and Vision Sciences, Sunnybrook Health Sciences Center, University of Toronto, Toronto, ON, Canada aff003;  Department of Ophthalmology, McMaster University, Hamilton, ON, Canada aff004;  University of Toronto Department of Ophthalmology and Visual Sciences, Mount Sinai Hospital, Toronto, ON, Canada aff005;  Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada aff006
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
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.

Klíčová slova:

Ethanol – Genetic testing – Human genetics – Mitochondria – Mitochondrial DNA – Optic neuropathy – Sensory perception – Vibration


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2019 Číslo 11