HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tzekov, R. T. Articles by Birch, D. G. Search for Related Content PubMed PubMed Citation Articles by Tzekov, R. T. Articles by Birch, D. G.

Autosomal Dominant Retinal Degeneration and Bone Loss in Patients with a 12-bp Deletion in the CRX Gene

¹ From the Retina Foundation of the Southwest, Dallas, Texas; the ² Departments of Ophthalmology, ³ Molecular Biology and Genetics, and ⁴ Neuroscience, John Hopkins University School of Medicine, Baltimore, Maryland; the ⁵ Human Genetics Center, and the ⁶ Department of Ophthalmology and Visual Science, The University of Texas Houston Health Science Center; and the ⁷ Jules Stein Eye Institute, University of California Los Angeles.

PURPOSE. To define the phenotypic expression of a deletion in the gene encoding the transcription factor CRX in a large, seven-generation, white family.

METHODS. Fourteen affected individuals, all heterozygous for the Leu146del12 mutation in the cone–rod homeobox gene (CRX), and four nonaffected relatives from the same family were examined with visual function tests, and 10 underwent bone mineral density (BMD) measurement.

RESULTS. The ability of the mutated CRX protein to transactivate rhodopsin promoter was decreased by approximately 25%, and its ability to react synergistically with neural retinal leucine zipper (NRL) was reduced by more than 30%. The affected members of the family had an autosomal dominant ocular condition most closely resembling Leber congenital amaurosis (LCA) with severe visual impairment at an early age. Depending on age, affected members showed varying degrees of significant visual acuity loss, elevated dark-adaptation thresholds, significantly reduced cone and rod electroretinogram (ERG) amplitudes, and progressive constriction of the visual fields, in most cases leading to complete blindness. Six affected members had reduced levels of BMD in the spine and the hip (osteopenia). Four affected female members who were receiving long-term hormonal replacement therapy (HRT) demonstrated normal values of BMD.

CONCLUSIONS. This large deletion of the CRX gene is associated with a severe form of autosomal dominant retinal degeneration. Affected members not receiving HRT showed reduced BMD (osteopenia). This phenotype may reflect the abnormal influence of mutant CRX on both retinal and pineal development.

This article has been cited by other articles:

				E. Vallespin, D. Cantalapiedra, R. Riveiro-Alvarez, R. Wilke, J. Aguirre-Lamban, A. Avila-Fernandez, M. A. Lopez-Martinez, A. Gimenez, M. Jose Trujillo-Tiebas, C. Ramos, et al. Mutation Screening of 299 Spanish Families with Retinal Dystrophies by Leber Congenital Amaurosis Genotyping Microarray Invest. Ophthalmol. Vis. Sci., December 1, 2007; 48(12): 5653 - 5661. [Abstract] [Full Text] [PDF]

				S. L. Whitaker and B. E. Knox Conserved Transcriptional Activators of the Xenopus Rhodopsin Gene J. Biol. Chem., November 19, 2004; 279(47): 49010 - 49018. [Abstract] [Full Text] [PDF]

				S. Dharmaraj, B. P. Leroy, M. M. Sohocki, R. K. Koenekoop, I. Perrault, K. Anwar, S. Khaliq, R. S. Devi, D. G. Birch, E. De Pool, et al. The Phenotype of Leber Congenital Amaurosis in Patients With AIPL1 Mutations Arch Ophthalmol, July 1, 2004; 122(7): 1029 - 1037. [Abstract] [Full Text] [PDF]

				R. T. Tzekov, K. G. Locke, D. C. Hood, and D. G. Birch Cone and Rod ERG Phototransduction Parameters in Retinitis Pigmentosa Invest. Ophthalmol. Vis. Sci., September 1, 2003; 44(9): 3993 - 4000. [Abstract] [Full Text] [PDF]

				S. Chen, Q.-L. Wang, S. Xu, I. Liu, L. Y. Li, Y. Wang, and D. J. Zack Functional analysis of cone-rod homeobox (CRX) mutations associated with retinal dystrophy Hum. Mol. Genet., April 15, 2002; 11(8): 873 - 884. [Abstract] [Full Text] [PDF]

				L. C. Bibb, J. K.L. Holt, E. E. Tarttelin, M. D. Hodges, K. Gregory-Evans, A. Rutherford, R. J. Lucas, J. C. Sowden, and C. Y. Gregory-Evans Temporal and spatial expression patterns of the CRX transcription factor and its downstream targets. Critical differences during human and mouse eye development. Hum. Mol. Genet., July 1, 2001; 10(15): 1571 - 1579. [Abstract] [Full Text] [PDF]