Ocular coloboma: Genetic variants reveal a dynamic model of eye development

Am J Med Genet C Semin Med Genet. 2020 Sep;184(3):590-610. doi: 10.1002/ajmg.c.31831. Epub 2020 Aug 27.


Ocular coloboma is a congenital disorder of the eye where a gap exists in the inferior retina, lens, iris, or optic nerve tissue. With a prevalence of 2-19 per 100,000 live births, coloboma, and microphthalmia, an associated ocular disorder, represent up to 10% of childhood blindness. It manifests due to the failure of choroid fissure closure during eye development, and it is a part of a spectrum of ocular disorders that include microphthalmia and anophthalmia. Use of genetic approaches from classical pedigree analyses to next generation sequencing has identified more than 40 loci that are associated with the causality of ocular coloboma. As we have expanded studies to include singleton cases, hereditability has been very challenging to prove. As such, researchers over the past 20 years, have unraveled the complex interrelationship amongst these 40 genes using vertebrate model organisms. Such research has greatly increased our understanding of eye development. These genes function to regulate initial specification of the eye field, migration of retinal precursors, patterning of the retina, neural crest cell biology, and activity of head mesoderm. This review will discuss the discovery of loci using patient data, their investigations in animal models, and the recent advances stemming from animal models that shed new light in patient diagnosis.

Keywords: MAC; anophthalmia; coloboma; eye development; microphthalmia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Child
  • Coloboma / genetics*
  • Coloboma / pathology
  • Eye / growth & development*
  • Eye / metabolism
  • Humans
  • Microphthalmos / genetics*
  • Microphthalmos / pathology
  • Neural Crest / growth & development
  • Neural Crest / metabolism
  • Organogenesis / genetics

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