Skip Navigation



Human Molecular Genetics Advance Access published online on November 16, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm337
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
17/5/656    most recent
ddm337v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Vithana, E. N
Right arrow Articles by Aung, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vithana, E. N
Right arrow Articles by Aung, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

SLC4A11 Mutations in Fuchs Endothelial Corneal Dystrophy (FECD)

Eranga N Vithana1,2,{dagger},*, Patricio E. Morgan3,{dagger}, Vedam Ramprasad4, Donald T.H. Tan1,2,5, Victor H.K Yong1, Divya Venkataraman1, Anandalakshmi Venkatraman1, Gary H. F. Yam6, Soumittra Nagasamy4, Ricky W. K. Law6, Rama Rajagopal7, Chi P. Pang6, Govindsamy Kumaramanickevel4, Joseph R. Casey3 and Tin Aung1,2,5

1 Singapore Eye Research Institute, 11 Third Hospital Avenue, Singapore 168751 2 Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597 3 Department of Physiology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada 4 ONGC Department of Genetics & Molecular biology, Vision Research Foundation, Sankara Nethralaya, 18 College road, Chennai - 6, Tamilnadu, India 5 Singapore National Eye Centre, Singapore 168751 6 Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, 147K Argyl Street, Kowloon, Hong Kong 7 Department of Cornea, Medical research foundation, Sankara Nethralaya, 18 College road, Chennai - 6, Tamilnadu, India

* To whom correspondence should be addressed at: Singapore Eye Research Institute, 11 Third Hospital Avenue, Singapore 168751. Tel: +65 6322 4542; Fax: +65 6322 4599; E-mail: evithana{at}yahoo.co.uk

Received July 12, 2007; Revised October 18, 2007; Accepted November 14, 2007

The endothelial (posterior) corneal dystrophies, which result from primary endothelial dysfunction, include Fuchs endothelial corneal dystrophy (FECD), posterior polymorphous corneal dystrophy (PPCD) and congenital hereditary endothelial dystrophy (CHED). Mutations in SLC4A11 gene have been recently identified in patients with recessive congenital hereditary endothelial dystrophy (CHED2). In this study, we show that heterozygous mutations in the SLC4A11 gene also cause late onset FECD. Four heterozygous mutations (three missense mutations (E399K, G709E and T754M) and one deletion mutation (c.99-100delTC) absent in ethnically matched controls were identified in a screen of 89 FECD patients. Missense mutations involved amino acid residues showing high interspecies conservation, indicating that mutations at these sites would be deleterious. Accordingly, immunoblot analysis, biochemical assay of cell surface localization and confocal immunolocalization showed that missense proteins encoded by the mutants were defective in localization to the cell surface. Our data suggests that SLC4A11 haploinsufficiency and gradual accumulation of the aberrant misfolded protein may play a role in FECD pathology and that reduced levels of SLC4A11 influence the long-term viability of the neural crest derived corneal endothelial cells.

{dagger} These authors should be regarded as Joint First Authors


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
L. Kao, P. Sassani, R. Azimov, A. Pushkin, N. Abuladze, J. Peti-Peterdi, W. Liu, D. Newman, and I. Kurtz
Oligomeric Structure and Minimal Functional Unit of the Electrogenic Sodium Bicarbonate Cotransporter NBCe1-A
J. Biol. Chem., September 26, 2008; 283(39): 26782 - 26794.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.