A NOVEL MISSENSE MUTATION IN THE RDS/PERIPHERIN GENE ASSOCIATED WITH RETINAL PATTERN DYSTROPHY Omar R. Ahmad, MD, Radha Ayyagari, PhD, David N. Zacks, MD, PhD Purpose: To present a case of retinal pattern dystrophy and the genetic analysis identifying the molecular basis of the disease. Methods: A 46-year-old man with a 6-year history of vision loss of the right eye. A clinical exam revealed pattern dystrophy of the retina bilaterally, with more involvement of the right eye. Results: Molecular diagnostic analysis of the retinal degeneration slow (RDS)/peripherin gene showed a novel change at nucleotide position 665 (G665C) that alters the amino acid at position 222 from cysteine to serine (C222S). Conclusion: This study describes an RDS/peripherin mutation in a case of retinal pattern dystrophy, which is the first identification of this mutation to our knowledge. RETINAL CASES & BRIEF REPORTS 4:84 – 85, 2010 From the Department of Ophthalmology and Visual Sciences, The Kellogg Eye Center, University of Mich- igan Medical School, Ann Arbor, Michigan. P attern dystrophy is a group of dominantly inher- ited photoreceptor dystrophies that often cause mild-to-moderate central vision disturbances in midlife. A variety of yellow, orange, or gray pigment deposi- tion patterns can be seen in the macula at the level of the retina pigment epithelium. Gass 1 subdivided pat- tern dystrophy according to the distribution of pig- ment in the macula: adult-onset foveomacular vitelli- form type, butterfly-shaped type, reticular type, multifocal pattern dystrophy simulating fundus flavi- maculatus, and fundus pulverulentus with contiguous changes. Pattern dystrophy is both phenotypically and genet- ically heterogeneous. Mutations in the retinal degen- eration slow (RDS)/peripherin gene are a not infre- quent cause of pattern dystrophy as well as other retinal diseases such as retinitis pigmentosa, retinitis punctata albescens, and cone-rod degeneration. 2–9 In fact, the same RDS/peripherin mutation within a sin- gle family can result in a number of different retinal phenotypes. 4 We describe a novel mutation of the RDS/ peripherin gene in a man with retinal pattern dystrophy. Case Report A 46-year-old white man presented with 6 years of decreased vision in the right eye. He noted that the vision loss was fairly sudden and that it affected primarily his central vision. He had no significant medical history but did report a family history of macular degeneration in his mother. On examination, visual acuity was 20/60 in the right eye and 20/20 in the left eye. Amsler grid testing showed a discrete area of central blurring on the right. Dilated examination showed yellow deposits in the central macula of both eyes, with greater involvement of the right eye (Figure 1). A clinical diagnosis of pattern dystrophy was made, and the patient agreed to have molecular diagnostic testing. Mutation analysis was carried out following guidelines of Clinical Laboratory Improvement Amendments. 10 The coding sequences of the RDS/peripherin gene (all three exons) were amplified by a polymerase chain reaction from genomic DNA. The resulting DNA fragments were directly sequenced using the same polymerase chain reaction primers. Molecular diagnostic analysis of the RDS/peripherin gene showed a heterozygous sequence change at nucleotide position 665 (G665C) that alters the amino acid at position 222 from cysteine to serine (C222S). This change was not been previously reported. The patient had 4 other changes in the heterozy- gous state RDS/peripherin gene (V106V, E304E, K310R, G338D) that have been previously reported as noncausative polymorphisms. The test confirmed a molecular diagnosis of pattern dystrophy due to a novel mutation in the RDS/peripherin gene. The authors have no proprietary interests or conflicts of interest. Reprint requests: Dr. David Zacks, MD, PhD, University of Michigan Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI 48105; e-mail: davzacks@umich.edu 84