IOVS Infection and Immunity
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

(Investigative Ophthalmology and Visual Science. 2004;45:4263-4267.)
© 2004 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.04-0078
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (16)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Maugeri, A.
Right arrow Articles by Zhang, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maugeri, A.
Right arrow Articles by Zhang, K.

A Novel Mutation in the ELOVL4 Gene Causes Autosomal Dominant Stargardt-like Macular Dystrophy

Alessandra Maugeri,1 Francoise Meire,2 Carel B. Hoyng,3 Carolien Vink,1 Nicole Van Regemorter,4 Goutam Karan,5 Zhenglin Yang,5,6 Frans P. M. Cremers,1,7 and Kang Zhang5,6,7

1From the Departments of Human Genetics and 3Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; the 2Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium; the 4Centre de Genetique ULB, Hopital Erasme, Bruxelles, Belgium; and the 5Department of Ophthalmology and Visual Science and the 6Program in Human Molecular Biology and Genetics, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, Utah.

PURPOSE. To conduct clinical and genetic studies in a European family with autosomal dominant Stargardt-like macular dystrophy (adSTGD-like MD) and to investigate the functional consequences of a novel ELOVL4 mutation.

METHODS. Ophthalmic examination and mutation screening by direct sequencing of the ELOVL4 gene was performed in two affected individuals. Wild-type and mutant ELOVL4 genes were expressed as enhanced green fluorescent protein (EGFP) fusion proteins in transient transfection in NIH-3T3 and HEK293 cells. To determine the subcellular localization of ELOVL4, an endoplasmic-reticulum (ER)–specific marker for pDsRed2-ER was cotransfected with ELOVL4 constructs. Transfected cells were viewed by confocal microscopy. Western blot analysis was performed to assess protein expression using an anti-GFP antibody.

RESULTS. Affected patients exhibited macular atrophy with surrounding flecks characteristic of adSTGD-like MD. A novel ELOVL4 p.Tyr270X mutation was detected in affected individuals. In cell-transfection studies, wild-type ELOVL4 localized preferentially to the ER. In contrast, the mutant protein appeared to be mislocalized within transfected cells.

CONCLUSIONS. In a European family with adSTGD-like MD, a novel ELOVL4 mutation was found to underlie the disorder. Transfection studies indicated that, unlike wild-type ELOVL4, the mutant protein does not localize to the ER but rather appears to be sequestered elsewhere in an aggregated pattern in the cytoplasm. Further analysis of the function of normal and mutant ELOVL4 will provide insight into the mechanism of macular degeneration.




This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
V. Vasireddy, Y. Uchida, N. Salem Jr, S. Y. Kim, M. N. A. Mandal, G. B. Reddy, R. Bodepudi, N. L. Alderson, J. C. Brown, H. Hama, et al.
Loss of functional ELOVL4 depletes very long-chain fatty acids (>=C28) and the unique {omega}-O-acylceramides in skin leading to neonatal death
Hum. Mol. Genet., March 1, 2007; 16(5): 471 - 482.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
V. Vasireddy, M. M. Jablonski, M. N. A. Mandal, D. Raz-Prag, X. F. Wang, L. Nizol, A. Iannaccone, D. C. Musch, R. A. Bush, N. Salem Jr, et al.
Elovl4 5-bp-Deletion Knock-in Mice Develop Progressive Photoreceptor Degeneration.
Invest. Ophthalmol. Vis. Sci., October 1, 2006; 47(10): 4558 - 4568.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
D. Raz-Prag, R. Ayyagari, R. N. Fariss, M. N. A. Mandal, V. Vasireddy, S. Majchrzak, A. L. Webber, R. A. Bush, N. Salem Jr, K. Petrukhin, et al.
Haploinsufficiency Is Not the Key Mechanism of Pathogenesis in a Heterozygous Elovl4 Knockout Mouse Model of STGD3 Disease.
Invest. Ophthalmol. Vis. Sci., August 1, 2006; 47(8): 3603 - 3611.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Grayson and R. S. Molday
Dominant Negative Mechanism Underlies Autosomal Dominant Stargardt-like Macular Dystrophy Linked to Mutations in ELOVL4
J. Biol. Chem., September 16, 2005; 280(37): 32521 - 32530.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
Y. P. Conley, A. Thalamuthu, J. Jakobsdottir, D. E. Weeks, T. Mah, R. E. Ferrell, and M. B. Gorin
Candidate gene analysis suggests a role for fatty acid biosynthesis and regulation of the complement system in the etiology of age-related maculopathy
Hum. Mol. Genet., July 15, 2005; 14(14): 1991 - 2002.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
G. Karan, C. Lillo, Z. Yang, D. J. Cameron, K. G. Locke, Y. Zhao, S. Thirumalaichary, C. Li, D. G. Birch, H. R. Vollmer-Snarr, et al.
Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor degeneration in mutant ELOVL4 transgenic mice: A model for macular degeneration
PNAS, March 15, 2005; 102(11): 4164 - 4169.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2004 by the Association for Research in Vision and Ophthalmology