Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/111827
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Type: Journal article
Title: Glaucoma spectrum and age-related prevalence of individuals with FOXC1 and PITX2 variants
Author: Souzeau, E.
Siggs, O.
Zhou, T.
Galanopoulos, A.
Hodson, T.
Taranath, D.
Mills, R.
Landers, J.
Pater, J.
Smith, J.
Elder, J.
Rait, J.
Giles, P.
Phakey, V.
Staffieri, S.
Kearns, L.
Dubowsky, A.
MacKey, D.
Hewitt, A.
Ruddle, J.
et al.
Citation: European Journal of Human Genetics, 2017; 25(7):839-847
Publisher: Natue Publishing Group
Issue Date: 2017
ISSN: 1018-4813
1476-5438
Statement of
Responsibility: 
Emmanuelle Souzeau, Owen M Siggs, Tiger Zhou, Anna Galanopoulos, Trevor Hodson, Deepa Taranath, Richard A Mills, John Landers, John Pater, James E Smith, James E Elder, Julian L Rait, Paul Giles, Vivek Phakey, Sandra E Staffieri, Lisa S Kearns, Andrew Dubowsky, David A Mackey, Alex W Hewitt, Jonathan B Ruddle, Kathryn P Burdon and Jamie E Craig
Abstract: Variation in FOXC1 and PITX2 is associated with Axenfeld-Rieger syndrome, characterised by structural defects of the anterior chamber of the eye and a range of systemic features. Approximately half of all affected individuals will develop glaucoma, but the age at diagnosis and the phenotypic spectrum have not been well defined. As phenotypic heterogeneity is common, we aimed to delineate the age-related penetrance and the full phenotypic spectrum of glaucoma in FOXC1 or PITX2 carriers recruited through a national disease registry. All coding exons of FOXC1 and PITX2 were directly sequenced and multiplex ligation-dependent probe amplification was performed to detect copy number variation. The cohort included 53 individuals from 24 families with disease-associated FOXC1 or PITX2 variants, including one individual diagnosed with primary congenital glaucoma and five with primary open-angle glaucoma. The overall prevalence of glaucoma was 58.5% and was similar for both genes (53.3% for FOXC1 vs 60.9% for PITX2, P=0.59), however, the median age at glaucoma diagnosis was significantly lower in FOXC1 (6.0±13.0 years) compared with PITX2 carriers (18.0±10.6 years, P=0.04). The penetrance at 10 years old was significantly lower in PITX2 than FOXC1 carriers (13.0% vs 42.9%, P=0.03) but became comparable at 25 years old (71.4% vs 57.7%, P=0.38). These findings have important implications for the genetic counselling of families affected by Axenfeld-Rieger syndrome, and also suggest that FOXC1 and PITX2 contribute to the genetic architecture of primary glaucoma subtypes.
Keywords: Glaucoma
Description: Published online 3 May 2017
Rights: © The Author(s) 2017. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission fromthe license holder to reproduce thematerial. To view a copy of this license, visit http://creativecommons.org/licenses/bync- nd/4.0/
RMID: 0030086335
DOI: 10.1038/ejhg.2017.59
Grant ID: http://purl.org/au-research/grants/nhmrc/1023911
Appears in Collections:Opthalmology & Visual Sciences publications

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