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Similar Phenotype in 12 Families

Susan M. Downes, FRCOphth; Frederick W. Fitzke, PhD; Graham E. Holder, PhD; Annette M. Payne, PhD; David A. R. Bessant, FRCOphth; Shomi S. Bhattacharya, PhD; Alan C. Bird, MD

Arch Ophthalmol. 1999;117:1373-1383.

Objective  To report the phenotype associated with the codon 172 RDS (gene for retinal degeneration slow) mutation in 11 separate families with an arginine-to-tryptophan substitution with common ancestry, and 1 family with an arginine-to-glutamine transition.

Patients  Screening for RDS gene mutations was performed in 400 subjects with autosomal dominant retinal degeneration. Twelve families were identified with a mutation in codon 172. Haplotype analysis was performed. Full ophthalmic evaluation was performed, including electrophysiologic and psychophysical investigation and imaging of autofluorescence using confocal laser scanning ophthalmoscopy.

Results  Haplotype analysis demonstrated that the 11 families were ancestrally related. All 12 families showed a common phenotype of macular dysfunction, with the deficit increasing with age. Abnormally high autofluorescence predated loss of visual acuity or visual field changes. Pattern electroretinographic (PERG) findings were affected early in disease. There was high intrafamilial and interfamilial consistency of phenotype.

Conclusion  These families demonstrate a striking conformity of symptoms and signs.

Clinical Relevance  In the codon 172 RDS mutation, unlike disease resulting from other RDS mutations, prediction of approximate age of onset and progression of visual deficit is possible. This should assist diagnosis and counseling.

From the Moorfields Eye Hospital (Drs Downes, Holder, Bessant, and Bird) and the Institute of Ophthalmology (Drs Downes, Fitzke, Payne, Bessant, Bhattacharya, and Bird), London, England.

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