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A Genetic, Clinical, and Histopathological Report

Kang Zhang, MD, PhD; Daniel C. Garibaldi, MD; Yang Li, MD; W. Richard Green, MD; Donald J. Zack, MD, PhD

Arch Ophthalmol. 2002;120:485-490.

Objectives  To identify the disease-causing mutation in a large family segregating dominantly inherited butterfly-shaped pattern dystrophy (BPD) and to describe the microscopic pathological changes observed in a member of this family.

Methods  Seventeen individuals at risk for dominantly inherited BPD in a family were examined and blood samples obtained. Linkage analysis and mutation screening of the human retinal degeneration slow (RDS)/peripherin locus were performed. Light and electron microscopic examinations were performed on 1 postmortem eye of 1 affected individual.

Results  Four individuals demonstrated macular degenerative changes with diminished visual acuity, and 3 others exhibited early signs of atrophy without visual deficits. Microscopic examination of the left eye of 1 patient revealed an area of total loss of the retinal pigment epithelium (RPE) and photoreceptor cell layer with intact choriocapillaris and lipofuscin-containing cells in the subretinal space. Outside the area of RPE atrophy, the RPE was greatly distended by lipofuscin. The disease locus in this family was mapped to 6p21.2, the region of the RDS/peripherin gene. Further analysis identified a GA change at nucleotide position 637 of RDS/peripherin, predicting a novel Cys213Tyr substitution in all affected members of the family.

Conclusions  This study describes a new RDS/peripherin mutation for BPD and provides the first combined genetic-pathological study of this condition, to our knowledge.

Clinical Relevance  Accumulation of lipofuscin in RPE is a prominent feature of several retinal disorders, including age-related macular degeneration. Further elucidation of the cellular and molecular mechanism of BPD may provide insight into pathogenesis and lead to novel treatment approaches for this and other macular degenerations.

From the Wilmer Eye Institute and the Departments of Ophthalmology (Drs Zhang, Garibaldi, Li, Green, and Zack), Molecular Biology and Genetics, and Neuroscience (Dr Zack), Johns Hopkins University School of Medicine, Baltimore, Md. Dr Zhang is now with the Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City. Dr Li is now with Tong Reng Eye Hospital, Beijing, China.

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