OCULAR FINDINGS ASSOCIATED WITH A CYS39ARG MUTATION IN THE NORRIE DISEASE GENE

Objective: To diagnose the carriers and noncarriers in a family affect ed with Norrie disease based on molecular analysis. Design: Family mem bers from three generations, including one affected patient, two oblig ate carriers, one carrier identified with linkage analysis, one noncar rier identified with linkage analysis, and one female family member wi th indeterminate carrier status, were examined clinically and electrop hysiologically. Linkage analysis had previously failed to determine th e carrier status of one female family member in the third generation. Blood samples were screened for mutations in the Norrie disease gene w ith single-strand conformation polymorphism analysis. The mutation was characterized by dideoxy-termination sequencing. Results: Ophthalmosc opy and electroretinographic examination failed to detect the carrier state, The affected individuals and carriers in this family were found to have a transition from thymidine to cytosine in the first nucleoti de of codon 39 of the Norrie disease gene, causing a cysteine-to-argin ine mutation. Single-strand conformation polymorphism analysis identif ied a patient of indeterminate status (by linkage) to be a noncarrier of Norrie disease. Conclusion: Ophthalmoscopy and electroretinography could not identify carriers of this Norrie disease mutation. Single-st rand conformation polymorphism analysis was more sensitive and specifi c than linkage analysis in identifying carriers in this family.