Autosomal dominant cone and cone-rod dystrophy with mutations in the guanylate cyclase activator 1A gene-encoding guanylate cyclase activating protein-1

Arch Ophthalmol. 2001 Jan;119(1):96-105.


Objective: To describe the phenotype in 3 families with dominantly inherited cone and cone-rod dystrophy with mutations in guanylate cyclase activator 1A (GUCA1A), the gene-encoding guanylate cyclase activator protein-1 (GCAP-1).

Methods: Phenotypic characterization with psychophysical and electrophysiological evaluation and confocal laser scanning ophthalmoscopy was performed in 2 families with a Tyr99Cys mutation and 1 family with a Pro50Leu mutation. Haplotype analysis was performed in the families with Tyr99Cys mutation.

Results: The families with a Y99C mutation were shown to be ancestrally related. Decreased visual acuity and loss of color vision occurred after the age of 20 years, followed by progressive atrophy of the central 5 degrees to 10 degrees. Electrophysiological testing revealed generalized loss of cone function, with preservation of rod function. Abnormal rod and cone sensitivities were confined to the central 5 degrees to 10 degrees. Confocal laser scanning ophthalmoscopy imaging showed abnormalities of autofluorescence in early disease. Subjects with a Pro50Leu mutation demonstrated marked variability in expressivity from minimal abnormalities of macular function to cone-rod dystrophy.

Conclusions: The phenotype associated with the Y99C mutation in GUCA1A is distinctive, with little variation in expression. By contrast, that associated with the P50L mutation demonstrates variable expressivity.

Clinical relevance: Phenotype-genotype correlation in these 2 mutations demonstrates 2 different phenotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Calcium-Binding Proteins / genetics*
  • Color Vision Defects / genetics
  • DNA / analysis
  • Electrooculography
  • Electroretinography
  • Female
  • Fluorescein Angiography
  • Genes, Dominant
  • Guanylate Cyclase / genetics*
  • Guanylate Cyclase-Activating Proteins
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Phenotype
  • Photoreceptor Cells, Vertebrate / pathology*
  • Point Mutation*
  • Retinal Degeneration / diagnosis
  • Retinal Degeneration / enzymology
  • Retinal Degeneration / genetics*
  • Visual Acuity
  • Visual Fields


  • Calcium-Binding Proteins
  • GUCA1A protein, human
  • Guanylate Cyclase-Activating Proteins
  • DNA
  • Guanylate Cyclase