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 Khani, S. C. Articles by Ayyagari, R. Search for Related Content PubMed PubMed Citation Articles by Khani, S. C. Articles by Ayyagari, R.

Late-Onset Autosomal Dominant Macular Dystrophy with Choroidal Neovascularization and Nonexudative Maculopathy Associated with Mutation in the RDS Gene

¹From the Department of Ophthalmology, State University of New York at Buffalo, Buffalo, New York; the ²Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan; the ³Departments of Ophthalmology, Pediatrics, Medicine, and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas; the ⁴Human Genetics Center and the Department of Ophthalmology, University of Texas Health Science Center, San Antonio, Texas; and the ⁵Department of Ophthalmology, New England Eye Center, Tufts University, Boston, Massachusetts.

PURPOSE. To examine the molecular genetic basis and phenotypic characteristics of an unusual late-onset autosomal dominant macular dystrophy with features of age-related macular degeneration (AMD) in a large family (SUNY901), by using linkage and mutation analyses.

METHODS. Blood samples were collected from 17 affected members, 17 clinically unaffected members, and 5 unrelated spouses. Clinical analyses included a review of medical history and standard ophthalmic examination with fundus photography, fluorescein angiography, and electroretinography. Linkage and haplotype analyses were performed with microsatellite markers. Mutation analysis was performed by amplification of exons followed by sequencing.

RESULTS. A wide spectrum of clinical phenotypes including exudative and nonexudative maculopathy was observed, with onset in the late fifth decade. Linkage analysis excluded most of the previously known maculopathy loci. Markers D6S1604 (Z_max of 3.18 at = 0), and D6S282 (Z_max of 3.18 at = 0) gave significant positive LOD scores and haplotype analysis localized the disease gene to a 9-centimorgan (cM) interval between markers D6S1616 and D6S459. Mutation analysis excluded the GUCA1A and GUCA1B genes and revealed a missense mutation in the RDS/peripherin gene leading to a Tyr141Cys substitution. A phenotype and haplotype comparison between this and a separate family with the Tyr141Cys mutation suggested the presence of a common ancestral haplotype.

CONCLUSIONS. The RDS mutation in codon 141 is associated with an unusual AMD-like late-onset maculopathy. An apparent selective bias was noted favoring the transmission of the mutant allele. These observations broaden the spectrum of phenotypes associated with RDS gene mutations.

This article has been cited by other articles:

				K. Downs, D. N. Zacks, R. Caruso, A. J. Karoukis, K. Branham, B. M. Yashar, M. H. Haimann, K. Trzupek, M. Meltzer, D. Blain, et al. Molecular Testing for Hereditary Retinal Disease as Part of Clinical Care Arch Ophthalmol, February 1, 2007; 125(2): 252 - 258. [Abstract] [Full Text] [PDF]

				B P Leroy, A Kailasanathan, J-J De Laey, G C M Black, and F D C Manson Intrafamilial phenotypic variability in families with RDS mutations: exclusion of ROM1 as a genetic modifier for those with retinitis pigmentosa Br. J. Ophthalmol., January 1, 2007; 91(1): 89 - 93. [Abstract] [Full Text] [PDF]

				M. N. A. Mandal, J. R. Heckenlively, T. Burch, L. Chen, V. Vasireddy, R. K. Koenekoop, P. A. Sieving, and R. Ayyagari Sequencing Arrays for Screening Multiple Genes Associated with Early-Onset Human Retinal Degenerations on a High-Throughput Platform Invest. Ophthalmol. Vis. Sci., September 1, 2005; 46(9): 3355 - 3362. [Abstract] [Full Text] [PDF]

				R. Ayyagari, M. N. A. Mandal, A. J. Karoukis, L. Chen, N. C. McLaren, M. Lichter, D. T. Wong, P. F. Hitchcock, R. C. Caruso, S. E. Moroi, et al. Late-Onset Macular Degeneration and Long Anterior Lens Zonules Result from a CTRP5 Gene Mutation Invest. Ophthalmol. Vis. Sci., September 1, 2005; 46(9): 3363 - 3371. [Abstract] [Full Text] [PDF]

				P J Francis, D W Schultz, A M Gregory, M B Schain, R Barra, J Majewski, J Ott, T Acott, R G Weleber, and M L Klein Genetic and phenotypic heterogeneity in pattern dystrophy Br. J. Ophthalmol., September 1, 2005; 89(9): 1115 - 1119. [Abstract] [Full Text] [PDF]