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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: 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:

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


Zdroje

1. Lenaers G, Hamel CP, Delettre C, Amati-Bonneau P, Procaccio V, Bonneau D, et al. Dominant optic atrophy. Orphanet J Rare Dis. 2012;7: 46. doi: 10.1186/1750-1172-7-46 22776096

2. Delettre-Cribaillet C, Hamel CP, Lenaers G. Optic atrophy type 1. GeneReviews®. University of Washington, Seattle; 1993. Available: http://www.ncbi.nlm.nih.gov/pubmed/20301426

3. Chun BY, Rizzo JF. Dominant optic atrophy: Updates on the pathophysiology and clinical manifestations of the optic atrophy 1 mutation. Curr Opin Ophthalmol. 2016;27: 475–480. doi: 10.1097/ICU.0000000000000314 27585216

4. Delettre C, Lenaers G, Griffoin J-M, Gigarel N, Lorenzo C, Belenguer P, et al. Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet. 2000;26: 207–210. doi: 10.1038/79936 11017079

5. Del Dotto V, Mishra P, Vidoni S, Fogazza M, Maresca A, Caporali L, et al. OPA1 isoforms in the hierarchical organization of mitochondrial functions. Cell Rep. 2017;19: 2557–2571. doi: 10.1016/j.celrep.2017.05.073 28636943

6. Jurkute N, Majander A, Bowman R, Votruba M, Abbs S, Acheson J, et al. Clinical utility gene card for: inherited optic neuropathies including next-generation sequencing-based approaches. Eur J Hum Genet. 2019;27: 494–502. doi: 10.1038/s41431-018-0235-y 30143805

7. Carelli V, Ghelli A, Zanna C, Baracca A, Sgarbi G, Martinuzzi A. Severe defect of complex I–dependent ATP synthesis shapes the mitochondria–driven path of apoptotic cell death in Leber’s hereditary optic neuropathy (LHON). Invest Ophthalmol Vis Sci. 2004;45: 1624–1624. Available: https://iovs.arvojournals.org/article.aspx?articleid=2407190

8. Yu-Wai-Man P, Votruba M, Burté F, La Morgia C, Barboni P, Carelli V. A neurodegenerative perspective on mitochondrial optic neuropathies. Acta Neuropathol. 2016;132: 789–806. doi: 10.1007/s00401-016-1625-2 27696015

9. Jurkute N, Majander A, Bowman R, Votruba M, Abbs S, Acheson J, et al. Clinical utility gene card for: inherited optic neuropathies including next-generation sequencing-based approaches. Eur J Hum Genet. 2019;27: 494–502. doi: 10.1038/s41431-018-0235-y 30143805

10. Amati-Bonneau P, Milea D, Bonneau D, Chevrollier A, Ferré M, Guillet V, et al. OPA1-associated disorders: Phenotypes and pathophysiology. Int J Biochem Cell Biol. 2009;41: 1855–1865. doi: 10.1016/j.biocel.2009.04.012 19389487

11. Majander A, Bowman R, Poulton J, Antcliff RJ, Reddy MA, Michaelides M, et al. Childhood-onset Leber hereditary optic neuropathy. Br J Ophthalmol. 2017;101: 1505–1509. doi: 10.1136/bjophthalmol-2016-310072 28314831

12. Manickam AH, Michael MJ, Ramasamy S. Mitochondrial genetics and therapeutic overview of Leber’s hereditary optic neuropathy. Indian J Ophthalmol. 2017;65: 1087–1092. doi: 10.4103/ijo.IJO_358_17 29133631

13. Kirkman MA, Yu-Wai-Man P, Korsten A, Leonhardt M, Dimitriadis K, De Coo IF, et al. Gene-environment interactions in Leber hereditary optic neuropathy. Brain. 2009;132: 2317–26. doi: 10.1093/brain/awp158 19525327

14. Carelli V, d’Adamo P, Valentino ML, La Morgia C, Ross-Cisneros FN, Caporali L, et al. Parsing the differences in affected with LHON: genetic versus environmental triggers of disease conversion. Brain. 2016;139: e17–e17. doi: 10.1093/brain/awv339 26657166

15. Scrimgeour EM, Dethlefs RF, Kevau I. Delayed recovery of vision after blindness caused by methanol poisoning. Med J Aust. 1982;2: 481–3. Available: http://www.ncbi.nlm.nih.gov/pubmed/7155031 7155031

16. Sullivan-Mee M, Solis K. Methanol-induced vision loss. J Am Optom Assoc. 1998;69: 57–65. Available: http://www.ncbi.nlm.nih.gov/pubmed/9479937 9479937

17. Grzybowski A, Zülsdorff M, Wilhelm H, Tonagel F. Toxic optic neuropathies: an updated review. Acta Ophthalmol. 2015;93: 402–410. doi: 10.1111/aos.12515 25159832

18. Shimozono M, Townsend JC, Ilsen PF, Bright DC. Acute vision loss resulting from complications of ethanol abuse. J Am Optom Assoc. 1998;69: 293–303. Available: http://www.ncbi.nlm.nih.gov/pubmed/9610037 9610037

19. Morris B, Votruba M. Leber’s optic neuropathy—visual return on alcohol cessation. Acta Ophthalmol. 2012;90: e568–e568. doi: 10.1111/j.1755-3768.2012.02387.x 22405409

20. Brooks PJ. DNA Damage, DNA Repair, and Alcohol Toxicity-A Review. Alcohol Clin Exp Res. 1997;21: 1073–1082. doi: 10.1111/j.1530-0277.1997.tb04256.x 9309320

21. Carelli V, Ross-Cisneros FN, Sadun AA. Optic nerve degeneration and mitochondrial dysfunction: genetic and acquired optic neuropathies. Neurochem Int. 2002;40: 573–84. Available: http://www.ncbi.nlm.nih.gov/pubmed/11850115 doi: 10.1016/s0197-0186(01)00129-2 11850115

22. Schenkel LC, Kerkhof J, Stuart A, Reilly J, Eng B, Woodside C, et al. Clinical next-generation sequencing pipeline outperforms a combined approach using sanger sequencing and multiplex ligation-dependent probe amplification in targeted gene panel analysis. J Mol Diagnostics. 2016;18: 657–667. doi: 10.1016/j.jmoldx.2016.04.002 27376475

23. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17: 405–423. doi: 10.1038/gim.2015.30 25741868

24. Services UD of H and H. Dietary guidelines for Americans 2015–2020. Skyhorse Publ Inc. 2017. Available: https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking

25. Yu-Wai-Man P, Griffiths PG, Gorman GS, Lourenco CM, Wright AF, Auer-Grumbach M, et al. Multi-system neurological disease is common in patients with OPA1 mutations. Brain. 2010;133: 771–786. doi: 10.1093/brain/awq007 20157015

26. Yu-Wai-Man P, Spyropoulos A, Duncan HJ, Guadagno J V., Chinnery PF. A multiple sclerosis-like disorder in patients with OPA1 mutations. Ann Clin Transl Neurol. 2016;3: 723–729. doi: 10.1002/acn3.323 27656661

27. Bargiela D, Chinnery PF. Mitochondria in neuroinflammation–Multiple sclerosis (MS), Leber hereditary optic neuropathy (LHON) and LHON-MS. Neurosci Lett. 2017; 132932. doi: 10.1016/j.neulet.2017.06.051 28668384

28. Abu-Amero KK, Bosley TM, Bohlega S, McLean D. Complex I respiratory defect in LHON plus dystonia with no mitochondrial DNA mutation. Br J Ophthalmol. 2005;89: 1380–1. doi: 10.1136/bjo.2005.072819 16170145

29. Metodiev MD, Gerber S, Hubert L, Delahodde A, Chretien D, Gérard X, et al. Mutations in the tricarboxylic acid cycle enzyme, aconitase 2, cause either isolated or syndromic optic neuropathy with encephalopathy and cerebellar atrophy. J Med Genet. 2014;51: 834–8. doi: 10.1136/jmedgenet-2014-102532 25351951

30. Ly TBN, Peters V, Gibson KM, Liesert M, Buckel W, Wilcken B, et al. Mutations in the AUH gene cause 3-methylglutaconic aciduria type I. Hum Mutat. 2003;21: 401–407. doi: 10.1002/humu.10202 12655555

31. Gunay-Aygun M, Huizing M, Anikster Y. OPA3-related 3-methylglutaconic aciduria. GeneReviews®. University of Washington, Seattle; 1993. Available: http://www.ncbi.nlm.nih.gov/pubmed/20301646

32. Votruba M, Moore AT, Bhattacharya SS, Votruba S Bhattacharya MS, Votruba M. Clinical features, molecular genetics, and pathophysiology of dominant optic atrophy. JMed Genet. 1998;35: 793–800. doi: 10.1136/jmg.35.10.793 9783700

33. Ferré M, Caignard A, Milea D, Leruez S, Cassereau J, Chevrollier A, et al. Improved locus-specific database for OPA1 mutations allows inclusion of advanced clinical data. Hum Mutat. 2015;36: 20–25. doi: 10.1002/humu.22703 25243597

34. Yu-Wai-Man FRCOphth P, Chinnery FRCP PF. Dominant Optic Atrophy: Novel OPA1 Mutations and Revised Prevalence Estimates. Ophthalmology. 2013. doi: 10.1016/j.ophtha.2013.04.022 23916084

35. Yu-Wai-Man P, Trenell MI, Hollingsworth KG, Griffiths PG, Chinnery PF. OPA1 mutations impair mitochondrial function in both pure and complicated dominant optic atrophy. Brain. 2011;134: e164. doi: 10.1093/brain/awq288 20952381

36. Barrett TG, Bundey SE, Macleod AF. Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet (London, England). 1995;346: 1458–63. Available: http://www.ncbi.nlm.nih.gov/pubmed/7490992

37. Urano F. Wolfram syndrome: Diagnosis, management, and treatment. Curr Diab Rep. 2016;16: 6. doi: 10.1007/s11892-015-0702-6 26742931

38. Gasparin MRR, Crispim F, Paula SL, Freire MBS, Dalbosco IS, Della Manna T, et al. Identification of novel mutations of the WFS1 gene in Brazilian patients with Wolfram syndrome. Eur J Endocrinol. 2009;160: 309–316. doi: 10.1530/EJE-08-0698 19042979

39. Zen PRG, Pinto LLC, Schwartz IVD, Barrett TG, Paskulin G. Report of a Brazilian patient with Wolfram Syndrome. J Pediatr (Rio J). 78: 529–32. Available: http://www.ncbi.nlm.nih.gov/pubmed/14647736

40. Astuti D, Sabir A, Fulton P, Zatyka M, Williams D, Hardy C, et al. Monogenic diabetes syndromes: Locus-specific databases for Alström, Wolfram, and Thiamine-responsive megaloblastic anemia. Hum Mutat. 2017;38: 764–777. doi: 10.1002/humu.23233 28432734

41. Grenier J, Meunier I, Daien V, Baudoin C, Halloy F, Bocquet B, et al. WFS1 in optic neuropathies: Mutation findings in nonsyndromic optic atrophy and assessment of clinical severity. Ophthalmology. 2016;123: 1989–1998. doi: 10.1016/j.ophtha.2016.05.036 27395765

42. Bansal V, Boehm BO, Darvasi A. Identification of a missense variant in the WFS1 gene that causes a mild form of Wolfram syndrome and is associated with risk for type 2 diabetes in Ashkenazi Jewish individuals. Diabetologia. 2018;61: 2180–2188. doi: 10.1007/s00125-018-4690-3 30014265

43. Zalloua PA, Azar ST, Delépine M, Makhoul NJ, Blanc H, Sanyoura M, et al. WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon. Hum Mol Genet. 2008;17: 4012–4021. doi: 10.1093/hmg/ddn304 18806274

44. Hardy C, Khanim F, Torres R, Scott-Brown M, Seller A, Poulton J, et al. Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1. Am J Hum Genet. 1999;65: 1279–90. doi: 10.1086/302609 10521293

45. Marelli C, Hamel C, Quiles M, Carlander B, Larrieu L, Delettre C, et al. ACO2 mutations: A novel phenotype associating severe optic atrophy and spastic paraplegia. Neurol Genet. 2018;4: e225. doi: 10.1212/NXG.0000000000000225 29564393

46. Srivastava S, Gubbels CS, Dies K, Fulton A, Yu T, Sahin M. Increased survival and partly preserved cognition in a patient with ACO2-related disease secondary to a novel variant. J Child Neurol. 2017;32: 840–845. doi: 10.1177/0883073817711527 28545339

47. Sharkia R, Wierenga KJ, Kessel A, Azem A, Bertini E, Carrozzo R, et al. Clinical, radiological, and genetic characteristics of 16 patients with ACO2 gene defects: Delineation of an emerging neurometabolic syndrome. J Inherit Metab Dis. 2019 [cited 22 Feb 2019]. doi: 10.1002/jimd.12022 30689204

48. Spiegel R, Pines O, Ta-Shma A, Burak E, Shaag A, Halvardson J, et al. Infantile cerebellar-retinal degeneration associated with a mutation in mitochondrial aconitase, ACO2. Am J Hum Genet. 2012;90: 518–23. doi: 10.1016/j.ajhg.2012.01.009 22405087

49. Kelman JC, Kamien BA, Murray NC, Goel H, Fraser CL, Grigg JR. A sibling study of isolated optic neuropathy associated with novel variants in the ACO2 gene. Ophthalmic Genet. 2018;39: 648–651. doi: 10.1080/13816810.2018.1509353 30118607

50. Man PYW, Turnbull DM, Chinnery PF. Leber hereditary optic neuropathy. J Med Genet. 2002;39: 162–169. doi: 10.1136/jmg.39.3.162 11897814

51. Riordan-Eva P, Sanders MD, Govan GG, Sweeney MG, Da Costa J, Harding AE. The clinical features of Leber’s hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation. Brain. 1995;118 (Pt 2: 319–37. Available: http://www.ncbi.nlm.nih.gov/pubmed/7735876

52. Chan C, Mackey DA, Byrne E. Sporadic Leber hereditary optic neuropathy in Australia and New Zealand. Aust N Z J Ophthalmol. 1996;24: 7–14. Available: doi: 10.1111/j.1442-9071.1996.tb01545.x 8742999

53. Verma IC, Paliwal P, Singh K. Genetic testing in pediatric ophthalmology. Indian J Pediatr. 2018;85: 228–236. doi: 10.1007/s12098-017-2453-7 28971364

54. Bajracharya K, Gautam P, Yadav SK, Shrestha N. Epidemiology and causes of optic atrophy in general outpatient department of lumbini eye institute. J Univers Coll Med Sci. 2016;3: 26–29. doi: 10.3126/jucms.v3i2.14287

55. Aviñó J, Díaz-Llopis M, España E, Johnsen-Soriano S, Romero B, Marín N, et al. Chronic ethanol feeding induces oxidative stress in the optic nerve of rats. Arch Soc Esp Oftalmol. 2002;77: 263–8. Available: http://www.ncbi.nlm.nih.gov/pubmed/12023745 12023745

56. Ahuja S, Kumar PS, Kumar VP, Kattimani S, Akkilagunta S. Effect of chronic alcohol and tobacco use on retinal nerve fibre layer thickness: a case–control study. BMJ Open Ophthalmol. 2016;1: e000003. doi: 10.1136/bmjophth-2016-000003 29354691

57. Maass J, Matthé E. Bilateral vision loss due to Leber’s hereditary optic neuropathy after long-term alcohol, nicotine and drug abuse. Doc Ophthalmol. 2018;136: 145–153. doi: 10.1007/s10633-018-9622-5 29372350

58. Morris B, Votruba M. Mean cellular volume in a patient with Leber’s optic neuropathy and visual return on alcohol cessation. Acta Ophthalmol. 2014;92: e77–e77. doi: 10.1111/aos.12100 23506347

59. Lenaers G, Hamel CP, Delettre C, Amati-Bonneau P, Procaccio V, Bonneau D, et al. Dominant optic atrophy. Orphanet J Rare Dis. 2012;7: 46. doi: 10.1186/1750-1172-7-46 22776096

60. Giordano L, Deceglie S, d’Adamo P, Valentino ML, La Morgia C, Fracasso F, et al. Cigarette toxicity triggers Leber’s hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation and ROS detoxification pathways. Cell Death Dis. 2015;6: e2021. doi: 10.1038/cddis.2015.364 26673666


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