A recurrent de novo mutation in ACTG1 causes isolated ocular coloboma

Rainger, Joe, Williamson, Kathleen A., Soares, Dinesh C. , Truch, Julia, Kurian, Dominic, Gillessen-Kaesbach, Gabriele, Seawright, Anne, Prendergast, James, Halachev, Mihail, Wheeler, Ann, McTeir, Lynn, Gill, Andrew C., van Heyningen, Veronica, Davey, Megan G. and FitzPatrick, David R. (2017) A recurrent de novo mutation in ACTG1 causes isolated ocular coloboma. Human Mutation, 38 (8). pp. 942-946. ISSN 1059-7794

Full content URL: http://doi.org/10.1002/humu.23246

"This is the peer reviewed version of the following article: Rainger J, Williamson KA, Soares DC, et al. A recurrent de novo mutation in ACTG1 causes isolated ocular coloboma. Human Mutation. 2017;38:942–946. https://doi.org/10.1002/humu.23246, which has been published in final form at https://doi.org/10.1002/humu.23246. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions."
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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 (WES) was used to analyze 12 trios (child affected with OC and both unaffected parents). This identified de novo mutations in 10 different genes in eight probands. Three of these genes encoded proteins associated with actin cytoskeleton dynamics: ACTG1, TWF1, and LCP1. Proband-only WES 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 resequencing 380 unrelated individuals with OC.

Keywords:ACTG1, eye development, ocular coloboma, tissue fusion, proteomics
Subjects:C Biological Sciences > C431 Medical Genetics
Divisions:College of Science
ID Code:29458
Deposited On:16 Nov 2017 14:41

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