RDS PERIPHERIN GENE-MUTATIONS ARE FREQUENT CAUSES OF CENTRAL RETINAL DYSTROPHIES/

Patients from 76 independent families with various forms of mostly cen tral retinal dystrophies were screened for mutations in the RDS/periph erin gene by means of SSCP analysis and direct DNA sequencing. Two non sense mutations (Gln239ter, Tyr285ter), five missense mutations (Arg17 2Trp, Lys197Glu, Gly208Asp, Trp246Arg, Ser289Leu), and one single base insertion (Gly208insG), heterozygous in all cases, were detected. Onl y one of these mutations, Arg172Trp, has been reported previously. Cos egregation of the mutation with the disease phenotype could be establi shed in selected families. Other missense mutations were excluded from a panel of 55-75 control subjects. The patients showed remarkable var iation in phenotype and disease expression not only between cases with mutations but also between affected members of the same family. This study indicates that RDS/peripherin mutations are a frequent cause of various types of central retinal dystrophies and that the RDS/peripher in gene exhibits a broad spectrum of allelic mutations. Comparative an alysis of known mutations allowed us to hypothesise that the deleterio us effect of RDS/peripherin gene mutations is the result of different molecular mechanisms.