Skip to main content
SpringerLink
Log in

Genetics in Glaucoma

  • Chapter
  • First Online:
Genetics of Ocular Diseases

  • 621 Accesses

Abstract

Glaucoma is known to be one of the common causes of blindness. This chapter discusses the role of genes in various types of glaucoma. While the genes involved in congenital and developmental glaucoma have been known, the search for definitive genes involved in pathology of adult onset glaucoma is still on. The genes myocilin and optineurin have been implicated in the pathogenesis of the adult onset open angle glaucoma in multiple studies. This chapter discusses the various genes including myocilin and optineurin which are associated with glaucoma, the process of identification, the strength of association and their future role in therapeutics.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Resnikoff S, Pascolini D, Etyaolin D, et al. Global data on visual impairment in the year 2002. Bull World Health Organ. 2004;82:844–51.

    PubMed  PubMed Central  Google Scholar 

  2. Sowden JC. Molecular and developmental mechanisms of anterior segment dysgenesis. Eye (Lond). 2007;21(10):1310–8.

    Article  CAS  Google Scholar 

  3. Wordinger RJ, Clark AF. Bone morphogenetic proteins and their receptors in the eye. Exp Biol Med (Maywood). 2007;232(8):979–92.

    Article  CAS  Google Scholar 

  4. Labelle-Dumais C, Pyatla G, Paylakhi S, et al. Loss of PRSS56 function leads to ocular angle defects and increased susceptibility to high intraocular pressure. Dis Model Mech. 2020;13(5):dmm 042853. Published 2020 May 29.

    Article  Google Scholar 

  5. von Graefe A. Pathology and treatment of glaucoma. Royal London Ophthalmic Hospital Rep J Ophthalmic Med Surg. 1871l Lon;7:108.

    Google Scholar 

  6. Duggal P, Klein AP, Lee KE, et al. A genetic contribution to intraocular pressure: the Beaver dam eye study. Investig Ophthalmol Vis Sci. 2005;46(2):555–60.

    Article  Google Scholar 

  7. Klein BE, Klein R, Lee KE. Heritability of risk factors for primary open-angle glaucoma: the Beaver Dam Eye Study. Investig Ophthalmol Vis Sci. 2004;45:59.

    Article  Google Scholar 

  8. Viswanathan AC, Hitchings RA, Indar A, et al. Commingling analysis of intraocular pressure and glaucoma in an older Australian population. Ann Hum Genet. 2004;68(Pt 5):489–97.

    Article  PubMed  Google Scholar 

  9. Charlesworth JC, Dyer TD, Stankovich JM, et al. Linkage to 10q22 for maximum intraocular pressure and 1p32 for maximum cup-to-disc ratio in an extended primary open-angle glaucoma pedigree. Investig Ophthalmol Vis Sci. 2005;46(10):3723–9.

    Article  Google Scholar 

  10. Rotimi CN, Chen G, Adeyemo AA, et al. Genome wide scan and fine mapping of quantitative trait loci for intraocular pressure on 5q and 14q in West Africans. Investig Ophthalmol Vis Sci. 2006;47(8):3262–7.

    Article  Google Scholar 

  11. Semina EV, Reiter R, Leysens NJ, et al. Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome. Nat Genet. 1996;14:392–9.

    Article  CAS  PubMed  Google Scholar 

  12. Mirzayans F, Gould DB, Heon E, et al. Axenfeld-Rieger syndrome resulting from mutation of the FKHL7 gene on chromosome 6p25. Eur J Hum Genet. 2000;8(1):71–4.

    Article  CAS  PubMed  Google Scholar 

  13. Phillips JC, del Bono EA, Haines JL, et al. A second locus for Rieger syndrome maps to chromosome 13q14. Am J Hum Genet. 1996;59(3):613–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Héon E, Sheth BP, Kalenak JW, et al. Linkage of autosomal dominant iris hypoplasia to the region of the Rieger syndrome locus. Hum Mol Gene. 1995;4:1435–9.

    Article  Google Scholar 

  15. Nishimura D, Swiderski R, Alward W, et al. The fork-head transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25. Nat Genet. 1998;19:140–7.

    Article  CAS  PubMed  Google Scholar 

  16. Mears AJ, Jordan T, Mirzayans F, et al. Mutations of the fork-head/winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly. Am J Hum Genet. 1998;63:1316–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ho CL, Walton DS. Primary congenital glaucoma: 2004 update. J Pediatr Ophthalmol Strabismus. 2004;41(5):271–88.

    Article  PubMed  Google Scholar 

  18. Zhao Y, Sorenson CM, Sheibani N. Cytochrome P4501B1 and primary congenital glaucoma. J Ophthalmic Vis Res. 2015;10:60–7.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Libby RT, Smith RS, Savinova OV, et al. Modification of ocular defects in mouse developmental glaucoma models by tyrosinase. Science. 2003;299:1578–81.

    Article  CAS  PubMed  Google Scholar 

  20. Sarfarazi M, Akarsu AN, Hossain A, Turacli ME, Aktan SG, Barsoum-Homsy M, et al. Assignment of a locus (GLC3A) for primary congenital glaucoma (Buphthalmos) to 2p21 and evidence for genetic heterogeneity. Genomics. 1995;30(2):171–7.

    Article  CAS  PubMed  Google Scholar 

  21. Akarsu AN, Turacli ME, Aktan SG, et al. A second locus (GLC3B) for primary congenital glaucoma (Buphthalmos) maps to the 1p36 region. Hum Mol Genet. 1996;5(8):1199–203.

    Article  CAS  PubMed  Google Scholar 

  22. Panicker SG, Reddy ABM, Mandal AK, Ahmed N, Nagarajaram HA, Hasnain SE, Balasubramanian D. Identification of novel mutations causing familial primary congenital glaucoma in Indian pedigrees. Investig Ophthalmol Vis Sci. 2002;43(5):1358–66.

    Google Scholar 

  23. Reddy ABM, Panicker SG, Mandal AK, Hasnain SE, Balasubramanian D. Identification of R368H as a predominant CYP1B1 allele causing primary congenital glaucoma in Indian patients. Investig Ophthalmol Vis Sci. 2003;44:4200–3.

    Article  Google Scholar 

  24. Reddy ABM, Kaur K, Mandal AK, Panicker SG, Thomas R, Hasnain SE, et al. Mutation spectrum of the CYP1B1 gene in Indian primary congenital glaucoma patients. Mol Vis. 2004;10:696–702.

    CAS  PubMed  Google Scholar 

  25. Narooie-Nejad M, Paylakhi SH, Shojaee S, Fazlali Z, Rezaei Kanavi M, Nilforushan N, et al. Loss of function mutations in the gene encoding latent transforming growth factor beta binding protein 2, LTBP2, cause primary congenital glaucoma. Hum Mol Genet. 2009;18(20):3969–77.

    Article  CAS  PubMed  Google Scholar 

  26. Ali M, McKibbin M, Booth A, Parry DA, Jain P, Riazuddin SA, et al. Null mutations in LTBP2 cause primary congenital glaucoma. Am J Hum Genet. 2009;84(5):664–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sud A, Del Bono EA, Haines JL, Wiggs JL. Fine mapping of the GLC1K juvenile primary open-angle glaucoma locus and exclusion of candidate genes. Mol Vis. 2008;14:1319–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Rajendrababu S, Gupta N, Vijayakumar B, Kumaragurupari R, Krishnadas SR. Screening first degree relatives of persons with primary open angle glaucoma in India. J Curr Glaucoma Pract. 2014;8(3):107–12.

    Article  PubMed  Google Scholar 

  29. Polansky JR, Fauss DJ, Chen P, et al. Cellular pharmacology and molecular biology of the trabecular meshwork inducible glucocorticoid response gene product. Ophthalmologica. 1997;211(3):126–39.

    Article  CAS  PubMed  Google Scholar 

  30. Kanagavalli J, Pandaranayaka E, Krishnadas SR, et al. In vitro and in vivo study on the secretion of the Gly367Arg mutant myocilin protein. Mol Vision. 2007;13:1161–8.

    CAS  Google Scholar 

  31. Kanagavalli J, Pandaranayaka E, Krishnadas SR, Krishnaswamy S, Sundaresan P. A review of genetic and structural understanding of the role of myocilin in primary open angle glaucoma. Indian J Ophthalmol. 2004;52(4):271–80.

    PubMed  Google Scholar 

  32. Abu-Amero K, Kondkar AA, Chalam KV. An updated review on the genetics of primary open angle glaucoma. Int J Mol Sci. 2015;16(12):28886–911.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wiggs JL, Kang JH, Yaspan BL, et al. Common variants near CAV1 and CAV2 are associated with primary open- angle glaucoma in Caucasians from USA. Hum Mol Genet. 2011;20:4707–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Stone EM, Fingert JH, Alward WL, Nguyen TD, Polansky JR, Sunden SL, et al. Identification of a gene that causes primary open angle glaucoma. Science. 1997;275:668–70.

    Article  CAS  PubMed  Google Scholar 

  35. Stoilova D, Child A, Trifan OC, Crick RP, Coakes RL, Sarfarazi M. Localization of a locus (GLC1B) for adult-onset primary open angle glaucoma to the 2cen-q13 region. Genomics. 1996;36(1):142–50.

    Article  CAS  PubMed  Google Scholar 

  36. Wirtz MK, Samples JR, Kramer PL, Rust K, Topinka JR, Yount J, et al. Mapping a gene for adultonset primary open-angle glaucoma to chromosome 3q. Am J Hum Genet. 1997;60:296–304.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Trifan OC, Traboulsi EI, Stoilova D, Alozie I, Nguyen R, Raja S, et al. A third locus (GLC1D) for adult-onset primary open-angle glaucoma maps to the 8q23 region. Am J Ophthalmol. 1998;126(1):17–28.

    Article  CAS  PubMed  Google Scholar 

  38. Sarfarazi M, Child A, Stoilova D, Brice G, Desai T, Trifan OC, et al. Localization of the fourth locus (GLC1E) for adult-onset primary open-angle glaucoma to the 10p15-p14 region. Am J Hum Genet. 1998;62(3):641–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Rezaie T, Child A, Hitchings R, Brice G, Miller L, Coca-Prados M, et al. Adult-onset primary open-angle glaucoma caused by mutations in optineurin. Science. 2002;295:1077–9.

    Article  CAS  PubMed  Google Scholar 

  40. Wirtz MK, Samples JR, Rust K, Lie J, Nordling L, Schilling K, et al. GLC1F, a new primary openangle glaucoma locus, maps to 7q35-q36. Arch Ophthalmol. 1999;117:237–41.

    Article  CAS  PubMed  Google Scholar 

  41. Pasutto F, Keller KE, Weisschuh N, Sticht H, Samples JR, Yang YF, et al. Variants in ASB10 are associated with open-angle glaucoma. Hum Mol Genet. 2012;21(6):1336–49.

    Article  CAS  PubMed  Google Scholar 

  42. Monemi S, Spaeth G, DaSilva A, Popinchalk S, Ilitchev E, Liebmann J, et al. Identification of a novel adult-onset primary open-angle glaucoma (POAG) gene on 5q22.1. Hum Mol Genet. 2005;14(6):725–33.

    Article  CAS  PubMed  Google Scholar 

  43. Suriyapperuma SP, Child A, Desai T, Brice G, Kerr A, Crick RP, et al. A new locus (GLC1H) for adult-onset primary open-angle glaucoma maps to the 2p15-p16 region. Arch Ophthalmol. 2007;125:86–92.

    Article  CAS  PubMed  Google Scholar 

  44. Allingham RR, Wiggs JL, Hauser ER, Larocque-Abramson KR, Santiago-Turla C, Broomer B, et al. Early adult-onset POAG linked to 15q11-13 using ordered subset analysis. Investig Ophthalmol Vis Sci. 2005;46(6):2002–5.

    Article  Google Scholar 

  45. Wiggs JL, Allingham RR, Hossain A, Kern J, Auguste J, DelBono EA, et al. Genome-wide scan for adult onset primary open angle glaucoma. Hum Mol Genet. 2000;9(7):1109–17.

    Article  CAS  PubMed  Google Scholar 

  46. Wiggs JL, Lynch S, Ynagi G, Maselli M, Auguste J, Del Bono EA, et al. A genome-wide scan identifies novel early-onset primary open-angle glaucoma loci on 9q22 and 20p12. Am J Hum Genet. 2004;74(6):1314–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Baird PN, Foote SJ, Mackey DA, Craig J, Speed TP, Bureau A. Evidence for a novel glaucoma locus at chromosome 3p21-22. Hum Genet. 2005;117(217):249–57.

    Article  CAS  PubMed  Google Scholar 

  48. Pang CP, Fan BJ, Canlas O, Wang DY, Dubois S, Tam PO, et al. A genome-wide scan maps a novel juvenile-onset primary open angle glaucoma locus to chromosome 5q. Mol Vis. 2006;12:85–92.

    CAS  PubMed  Google Scholar 

  49. Wang DY, Fan BJ, Chua JK, Tam PO, Leung CK, Lam DS, et al. A genome-wide scan maps a novel juvenile-onset primary open-angle glaucoma locus to 15q. Investig Ophthalmol Vis Sci. 2006;47(12):5315–21.

    Article  Google Scholar 

  50. Pasutto F, Matsumoto T, Mardin CY, Sticht H, Brandsttool JH, Michels-Rautenstrauss K, et al. Heterozygous NTF4 mutations impairing neurotrophin-4 signalling in patients with primary open-angle glaucoma. Am J Hum Genet. 2009;85(4):447–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Fingert JH, Robin AL, Stone JL, Roos BR, Davis LK, Scheetz TE, et al. Copy number variations on chromosome 12q14 in patients with normal tension glaucoma. Hum Mol Genet. 2011;20(12):2482–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kanagavalli J, Pandaranayaka E, Krishnadas SR, et al. Evaluation and understanding of myocilin mutations in Indian primary open angle glaucoma patients. Mol Vision. 2003;9:606–14.

    CAS  Google Scholar 

  53. Pandaranayaka PJ, Prasanthi N, Kannabiran N, et al. Polymorphisms in an intronic region of the myocilin gene associated with primary open-angle glaucoma--a possible role for alternate splicing. Mol Vis. 2010;16:2891–902. Published 2010 Dec 29.

    PubMed  PubMed Central  Google Scholar 

  54. Kader MA, Namburi P, Ramugade S, et al. Clinical and genetic characterization of a large primary open angle glaucoma pedigree. Ophthalmic Genet. 2017;38(3):222–5.

    Article  PubMed  Google Scholar 

  55. Kavitha S, Zebardast N, Palaniswamy K, et al. Family history is a strong risk factor for prevalent angle closure in a South Indian population. Ophthalmology. 2014;121(11):2091–7.

    Article  PubMed  Google Scholar 

  56. Vithana EN, Khor CC, Qiao C, et al. Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma. Nat Genet. 2012;44(10):1142–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Khor CC, Do T, Jia H, et al. Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma. Nat Genet. 2016;48(5):556–62.

    Article  CAS  PubMed  Google Scholar 

  58. Duvesh R, Verma A, Venkatesh R, et al. Association study in a South Indian population supports rs1015213 as a risk factor for primary angle closure. Investig Ophthalmol Vis Sci. 2013;54:5624–8.

    Article  CAS  Google Scholar 

  59. Prof. Tin Aung, Singapore National Eye Centre, National University of Singapore- Proceedings of All India Ophthalmology Conference 2020.

    Google Scholar 

  60. Osborne A, Khatib TZ, Songra L, et al. Neuroprotection of retinal ganglion cells by a novel gene therapy construct that achieves sustained enhancement of brain-derived neurotrophic factor/tropomyosin-related kinase receptor-B signalling. Cell Death Dis. 2018;9(10):1007.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Konda SM, Kiland JA, Mohr M, et al. Schlemmath Dis. of retinal ganglion asurement, catheterization and substance delivery in live monkeys. Investig Ophthalmol Vis Sci July. 2019;60:1788.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Swamy Eye Clinic, Chennai, Tamilnadu, India

    Mohana Sinnasamy & C. Praveena

  2. Department of Ophthalmology, Sundaram Medical Foundation, Chennai, Tamilnadu, India

    Murali Ariga

  3. Department of Glaucoma, Aravind Eye Hospital, Madurai, Tamilnadu, India

    Sharmila Rajendrababu

Authors
  1. Mohana Sinnasamy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Murali Ariga
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Praveena
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sharmila Rajendrababu
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Madhya Pradesh, India

    H. V. Nema

  2. Department of Ophthalmology, Sri Aurobindo Medical College and PG Institute, Indore, Madhya Pradesh, India

    Nitin Nema

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Sinnasamy, M., Ariga, M., Praveena, C., Rajendrababu, S. (2022). Genetics in Glaucoma. In: Nema, H.V., Nema, N. (eds) Genetics of Ocular Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-16-4247-0_7

Download citation

  • DOI: https://doi.org/10.1007/978-981-16-4247-0_7

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-16-4246-3

  • Online ISBN: 978-981-16-4247-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation