Autosomal dominant cone-rod dystrophy with mutations in the guanylate cyclase 2D gene encoding retinal guanylate cyclase-1.

OBJECTIVE

To describe the phenotype in 4 families with dominantly inherited cone-rod dystrophy, 1 with an R838C mutation and 1 with an R838H mutation in the guanylate cyclase 2D (GUCY2D) gene encoding retinal guanylate cyclase-1.

METHODS

Psychophysical and electrophysiological evaluation and confocal laser scanning ophthalmoscopic imaging was performed on 10 affected members of 4 British families.

RESULTS

Although subjects had lifelong poor vision in bright light, a major reduction in visual acuity did not occur in most of them until after their late teens. Fundus abnormalities were confined to the central macula, and increasing central atrophy was noted with age. Increased background autofluorescence was observed surrounding the central atrophic area. Electrophysiological testing revealed a marked loss of cone function with only minimal rod involvement, even in older subjects. Photopic and scotopic static perimetry demonstrated central and peripheral cone-mediated threshold elevations with midperipheral sparing.

CONCLUSION

The phenotype associated with autosomal dominant cone-rod dystrophy with either an R838C or R838H mutation in GUCY2D is distinctive, with predominantly cone system involvement. There is some variation in severity within the 3 families with the R838C mutation.

CLINICAL RELEVANCE

Families with the R838C or R838H mutation have a much milder phenotype than the family previously described that had 2 sequence changes, E837D and R838S, in GUCY2D.