X-linked exudative vitreoretinopathy caused by an arginine to leucine substitution (R121L) in the Norrie disease protein

We report the cosegregation of an arginine to leucine substitution at position 121 of the Norrie disease protein in a large kindred where exudative vitreoretinopathy segregates as an X-linked recessive trait. The clinical phenotype and rate of disease progression were extremely variable, with progression to total retinal detachment from less than age 2 years to more than 21 years. To date, all mutations in X-linked vitreoretinopathy have been missense mutations, presumably not affecting the three-dimensional structure of the NDP gene product, and clustered around residues 121-126 of the Norrie protein. This contrasts with the diversity of mutations seen in the more severe, allelic Norrie disease.