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Glaucoma spectrum and age-related prevalence of individuals with FOXC1 and PITX2 variants

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 spectru...

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Autores principales: Souzeau, Emmanuelle, Siggs, Owen M, Zhou, Tiger, Galanopoulos, Anna, Hodson, Trevor, Taranath, Deepa, Mills, Richard A, Landers, John, Pater, John, Smith, James E, Elder, James E, Rait, Julian L, Giles, Paul, Phakey, Vivek, Staffieri, Sandra E, Kearns, Lisa S, Dubowsky, Andrew, Mackey, David A, Hewitt, Alex W, Ruddle, Jonathan B, Burdon, Kathryn P, Craig, Jamie E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520071/
https://www.ncbi.nlm.nih.gov/pubmed/28513611
http://dx.doi.org/10.1038/ejhg.2017.59
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author Souzeau, Emmanuelle
Siggs, Owen M
Zhou, Tiger
Galanopoulos, Anna
Hodson, Trevor
Taranath, Deepa
Mills, Richard A
Landers, John
Pater, John
Smith, James E
Elder, James E
Rait, Julian L
Giles, Paul
Phakey, Vivek
Staffieri, Sandra E
Kearns, Lisa S
Dubowsky, Andrew
Mackey, David A
Hewitt, Alex W
Ruddle, Jonathan B
Burdon, Kathryn P
Craig, Jamie E
author_facet Souzeau, Emmanuelle
Siggs, Owen M
Zhou, Tiger
Galanopoulos, Anna
Hodson, Trevor
Taranath, Deepa
Mills, Richard A
Landers, John
Pater, John
Smith, James E
Elder, James E
Rait, Julian L
Giles, Paul
Phakey, Vivek
Staffieri, Sandra E
Kearns, Lisa S
Dubowsky, Andrew
Mackey, David A
Hewitt, Alex W
Ruddle, Jonathan B
Burdon, Kathryn P
Craig, Jamie E
author_sort Souzeau, Emmanuelle
collection PubMed
description 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.
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spelling pubmed-55200712017-09-18 Glaucoma spectrum and age-related prevalence of individuals with FOXC1 and PITX2 variants Souzeau, Emmanuelle Siggs, Owen M Zhou, Tiger Galanopoulos, Anna Hodson, Trevor Taranath, Deepa Mills, Richard A Landers, John Pater, John Smith, James E Elder, James E Rait, Julian L Giles, Paul Phakey, Vivek Staffieri, Sandra E Kearns, Lisa S Dubowsky, Andrew Mackey, David A Hewitt, Alex W Ruddle, Jonathan B Burdon, Kathryn P Craig, Jamie E Eur J Hum Genet Article 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. Nature Publishing Group 2017-07 2017-05-03 /pmc/articles/PMC5520071/ /pubmed/28513611 http://dx.doi.org/10.1038/ejhg.2017.59 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ 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 from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Article
Souzeau, Emmanuelle
Siggs, Owen M
Zhou, Tiger
Galanopoulos, Anna
Hodson, Trevor
Taranath, Deepa
Mills, Richard A
Landers, John
Pater, John
Smith, James E
Elder, James E
Rait, Julian L
Giles, Paul
Phakey, Vivek
Staffieri, Sandra E
Kearns, Lisa S
Dubowsky, Andrew
Mackey, David A
Hewitt, Alex W
Ruddle, Jonathan B
Burdon, Kathryn P
Craig, Jamie E
Glaucoma spectrum and age-related prevalence of individuals with FOXC1 and PITX2 variants
title Glaucoma spectrum and age-related prevalence of individuals with FOXC1 and PITX2 variants
title_full Glaucoma spectrum and age-related prevalence of individuals with FOXC1 and PITX2 variants
title_fullStr Glaucoma spectrum and age-related prevalence of individuals with FOXC1 and PITX2 variants
title_full_unstemmed Glaucoma spectrum and age-related prevalence of individuals with FOXC1 and PITX2 variants
title_short Glaucoma spectrum and age-related prevalence of individuals with FOXC1 and PITX2 variants
title_sort glaucoma spectrum and age-related prevalence of individuals with foxc1 and pitx2 variants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520071/
https://www.ncbi.nlm.nih.gov/pubmed/28513611
http://dx.doi.org/10.1038/ejhg.2017.59
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