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

English version

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
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0225656

Souhrn

Purpose

To assess the clinical utility of next-generation sequencing (NGS) for the diagnosis of patients with optic atrophy (OA).

Design

Retrospective cohort study.

Methods

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.

Results

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).

Conclusions

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:

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

Zdroje

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