A recurrent de novo mutation in ACTG1 causes isolated ocular coloboma

Jonathan Rainger, Kathy Williamson, Dinesh Soares, Julia Truch, Dominic Thekkedath Kurian, Gabriele Gillessen-Kaesbach, Anne Seawright, James Prendergast, Mihail Halachev, Ann Wheeler, Lynn McTeir, Andrew Gill, Veronica Van Heyningen, Megan Davey, UK10K, David R FitzPatrick

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Ocular coloboma (OC) is a defect in optic fissure closure and is a common cause
of severe congenital visual impairment. Bilateral OC is primarily genetically determined and shows marked locus heterogeneity. Whole exome sequencing was used to analyse twelve trios (child affected with OC and both unaffected parents), This identified de novo mutations in ten different genes in eight probands. Three of these genes encoded proteins associated with actin cytoskeleton dynamics: ACTG1, TWF1 and LCP1. Proband-only whole exome sequencing identified a second unrelated individual with isolated OC carrying the same ACTG1 allele, encoding p.(Pro70Leu). Both individuals have normal neurodevelopment with no extra-ocular signs of Baraitser Winter syndrome. We found this mutant protein to be incapable of incorporation into F-actin. The LCP1 and TWF1 variants each resulted in only minor disturbance of actin-interactions and no further plausibly causative variants were identified in these genes on re-sequencing 380 unrelated individuals with OC.
Original languageEnglish
Pages (from-to)942-946
JournalHuman Mutation: Variation, Informatics and Disease
Issue number8
Early online date11 May 2017
Publication statusPublished - Aug 2017

Keywords / Materials (for Non-textual outputs)

  • Ocular Coloboma
  • Actin
  • ACTG1
  • eye development
  • tissue fusion


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