Full characterization of the maculopathy associated with an Arg-172-Trp mutation in the RDS/peripherin gene

The objective of this study was to fully characterize the macular dystrophy phenotype and genotype in a large family of the Zermatt area of Switzerland. Clinical and molecular studies of the family included a comprehensive eye examination and a mutational analysis of the RDS, rhodopsin, and TIMP-3 genes. In selected cases, fluorescein angiography, perimetry, and electroretinography were performed. Forty-two family members at risk of expressing the maculopathy were studied. Of these, 24 were found to be clinically affected. The severity of macular disease in these patients was clearly age-related and different stages of progression were identified. Central pigmentary alterations were seen in adolescent patients, while patients in their late teens and twenties exhibited drusen-like deposits. Later, these defects formed focal areas of atrophy which eventually led to central geographic atrophy with severe visual loss by the fifth decade and cone-rod dysfunction. The transmission of this condition is autosomal dominant with complete penetrance. The underlying genetic defect is a mutation in codon 172 of the RDS/peripherin gene, a gene expressed in both rods and cones, which results in the substitution of tryptophan for an arginine residue at that position. 'Zermatt macular dystrophy' is a dominant, age-related, progressive macular dystrophy which in later stages resembles atrophic age-related macular degeneration. The size of the family studied allowed definition of the clinical spectrum of this condition and identification of the related genetic defect which allows more precise diagnosis and counseling.