PHENOTYPIC-EXPRESSION OF AUTOSOMAL-DOMINANT RETINITIS-PIGMENTOSA IN ASWEDISH FAMILY EXPRESSING A PHE-211-LEU VARIANT OF PERIPHERIN RDS/

Purpose: To characterize the clinical phenotype, with emphasis on elec trophysiology, of members of a Swedish family with autosomal dominant retinitis pigmentosa due to a novel mutation, F211L, in the peripherin /RDS gene. Methods: Nine patients with autosomal dominant retinitis pi gmentosa and two healthy family members underwent a full clinical eval uation including kinetic visual field testing, measurement of dark ada ptation threshold, and full-field electroretinography. Blood samples w ere collected and DNA analysis was performed using denaturing gradient gel electrophoresis (DGGE). Results: The grandfather, six of seven si blings from the middle generation, and two young boys carried the muta tion F211L in the peripherin/RDS gene. The mutation segregated with th e clinical presentation of disease. Fundus examination revealed mainly macular atrophy. All assessed parameters of retinal function (visual acuity, dark adaptation threshold, visual fields, and full-field elect roretinograms) demonstrated a successive reduction with increasing age . Full-field electroretinograms showed a diminished rod response in al l affected individuals and a reduction of the cone b-wave amplitudes w ith increasing age, indicating retinitis pigmentosa. In the affected f amily members, the disease seems to progress at a similar rate with in creasing age. Conclusions: The peripherin/RDS gene mutation F211L is a ssociated with a clinical phenotype and includes early loss of rod fun ction and successive reduction of cone function with increasing age, b ut impressively well-preserved visual acuity and visual fields in youn g and middle-aged patients and moderately reduced vision in the old pa tient, Compared to previously described phenotypes segregating with mu tations in the peripherin/RDS gene. the present family demonstrates a more benign clinical phenotype, which is concordant within the family.