Serine-27-phenylalanine mutation within the peripherin/RDS gene in a family with cone dystrophy

Purpose: To evaluate the clinical and electrophysiologic findings in a family with two heterozygous sequence changes in the peripherin-retinal degeneration slow (RDS) gene. Methods: A family study was done of a pedigree obtained by screening for rhodopsin, peripherin/RDS, or rom-l gene mutations in probands from families with hereditary retinal diseases. The patients consisted of three affected and four unaffected members from a family with cone dystrophy. Ophthalmoscopy, visual field testing, electroretinography, and DNA analysis were performed. Results: Denaturing gradient gel electrophoresis showed the presence of two different sequence changes in the RDS genes of this family. In three members with a retinal disease, the authors observed the substitution of phenylalanine for serine in codon 27 (serine-27-phenylalanine). The clinical and functional findings in these three patients were most consistent with autosomal-dominant cone dystrophy. Three other family members, unaffected with retinal disease, were found to show a substitution of serine for cysteine in codon 72 of the peripherin protein. Conclusion: A peripherin/RDS sequence change may produce a cone dystrophy with minimal ophthalmoscopic changes in the macula and limited peripheral degenerative changes. Caution is warranted to avoid ascribing nondisease-causing sequence polymorphisms in candidate genes as responsible for determining the development of a retinal disease phenotype.