DETECTION OF ALTERATIONS IN ALL 3 EXONS OF THE PERIPHERIN RDS GENE INSWEDISH PATIENTS WITH RETINITIS-PIGMENTOSA USING AN EFFICIENT DGGE SYSTEM/

Aims-To develop a sensitive mutation screening procedure suitable for routine analysis of the peripherin/RDS gene, and to estimate the natur e and prevalence of peripherin/RDS gene mutations in Swedish patients with autosomal dominant retinitis pigmentosa. Methods-To make the meth od as sensitive as possible, as many as eight segments, covering the t hree exons and the flanking intron sequences of the peripherin/RDS gen e, were analysed by denaturing gradient gel electrophoresis. A group o f 38 Swedish patients with a clinical diagnosis of autosomal dominant retinitis pigmentosa were screened for mutations in the peripherin/RDS gene. Results-Three point mutations were found in four of the patient s and five polymorphisms were defined. One mutation in exon 1, R172W, has been described previously in other ethnic groups as causing a macu lar degeneration. Another mutation, in exon 2 and causing the substitu tion F211L, was found in two unrelated patients. A third mutation, res ulting in the likely non-pathogenic substitution S289L, as well as a p olymorphism not reported previously, was found in exon 3. Conclusions- The screening procedure described allows detection of mutations in all of the exons, including the polymorphic 5' and 3' ends of the gene, a nd is therefore suitable for routine screening of peripherin/RDS gene defects in patients with autosomal dominant retinitis pigmentosa. The frequency of mutations found in the Swedish patient group indicates th at defects in the peripherin/RDS gene might be a more common cause of autosomal dominant retinitis pigmentosa than was thought previously.