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December 1994

Ocular Findings Associated With a Cys39Arg Mutation in the Norrie Disease Gene

Author Affiliations

From the Department of Ophthalmology, The University of Iowa, Iowa City (Drs Joos, Kimura, and Stone and Ms Vandenburgh); The Bascom Palmer Eye Institute, University of Miami (Fla) School of Medicine (Dr Joos); and Integrated Genetics, Signal Hill, Calif (Dr Bartley).; Dr Stone is a Research to Prevent Blindness Dolly Green Scholar. Dr Joos is now with the Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, Tenn.

Arch Ophthalmol. 1994;112(12):1574-1579. doi:10.1001/archopht.1994.01090240080029

Objective:  To diagnose the carriers and noncarriers in a family affected with Norrie disease based on molecular analysis.

Design:  Family members from three generations, including one affected patient, two obligate carriers, one carrier identified with linkage analysis, one noncarrier identified with linkage analysis, and one female family member with indeterminate carrier status, were examined clinically and electrophysiologically. Linkage analysis had previously failed to determine the carrier status of one female family member in the third generation. Blood samples were screened for mutations in the Norrie disease gene with single-strand conformation polymorphism analysis. The mutation was characterized by dideoxy-termination sequencing.

Results:  Ophthalmoscopy 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 nucleotide of codon 39 of the Norrie disease gene, causing a cysteine-to-arginine mutation. Single-strand conformation polymorphism analysis identified 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-strand conformation polymorphism analysis was more sensitive and specific than linkage analysis in identifying carriers in this family.

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