Sm. Downes et al., Autosomal dominant cone and cone-rod dystrophy with mutations in the guanylate cyclase activator 1A gene-encoding guanylate cyclase activating protein-1, ARCH OPHTH, 119(1), 2001, pp. 96-105
Objective: To describe the phenotype in 3 families with dominantly inherite
d cone and cone-rod dystrophy with mutations in guanylate cyclase activator
1A (GUCA1A), the gene-encoding guanylate cyclase activator protein-1 (GCAP
Methods: Phenotypic characterization with psychophysical and electrophysiol
ogical evaluation and confocal laser scanning ophthalmoscopy was performed
in 2 families with a Tyr99Cys mutation and 1 family with a Pro50Leu mutatio
n. Haplotype analysis was performed in the families with Tyr99Cys mutation.
Results: The families with a Y99C mutation were shown to be ancestrally rel
ated. Decreased visual acuity and loss of color vision occurred after the a
ge of 20 years, followed by progressive. atrophy of the central 5 degrees t
o 10 degrees. Electrophysiological testing revealed generalized loss of con
e function, with preservation of rod function. Abnormal rod and cone sensit
ivities were confined to the central 5 degrees to 10 degrees. Confocal lase
r scanning ophthalmoscopy imaging, showed abnormalities of autofluorescence
in tarry disease. Subjects with a Pro50Leu mutation demonstrated marked va
riability in expressivity from minimal abnormalities of macular function to
Conclusions: The phenotype associated with the Y99C mutation in GUCA1A is d
istinctive, with little variation in expression. By contrast, that associat
ed with the P50L mutation demonstrates variable expressivity.
Clinical Relevance: Phenotype-genotype correlation in these 2 mutations dem
onstrates 2 different phenotypes.