Ocular findings associated with a Cys39Arg mutation in the Norrie disease gene
K. M. Joos, A. E. Kimura, K. Vandenburgh, J. A. Bartley and E. M. Stone
Department of Ophthalmology, University of Iowa, Iowa City.
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.
