Objective: To describe the phenotype in 4 families with dominantly inherite
d cone-rod dystrophy, 1 with an R838C mutation and 1 with an R838H mutation
in the guanylate cyclase 2D (GUCY2D) gene encoding retinal guanylate cycla
Methods: Psychophysical and electrophysiological evaluation and confocal la
ser scanning ophthalmoscopic imaging was performed on 10 affected members o
f 4 British families.
Results: Although subjects had lifelong poor vision in bright light, a majo
r reduction in visual acuity did not occur in most of them until after thei
r late teens. Fundus abnormalities were confined to the central macula, and
increasing central atrophy was noted with age. Increased background autofl
uorescence was observed surrounding the central atrophic area. Electrophysi
ological testing revealed a marked loss of cone function with only minimal
rod involvement, even in older subjects. Photopic and scotopic static perim
etry demonstrated central and peripheral cone-mediated threshold elevations
with midperipheral sparing.
Conclusion: The phenotype associated with autosomal dominant cone-rod dystr
ophy 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 m
ilder phenotype than the family previously described that had 2 sequence ch
anges, E837D and R838S, in GUCY2D.