Genotypes and phenotypes of genes associated with achromatopsia: A reference for clinical genetic testing

Mol Vis. 2020 Aug 22:26:588-602. eCollection 2020.


Purpose: Achromatopsia is a congenital autosomal recessive cone disorder, and it has been found to be associated with six genes. However, pathogenic variants in these six genes have been identified in patients with various retinal dystrophies with the exception of achromatopsia. Thus, this study aims to investigate the contribution of these genes in hereditary retinal diseases and the potential genotype-phenotype correlations.

Methods: Biallelic variants in six achromatopsia-related genes, namely, CNGA3, CNGB3, GNAT2, ATF6, PDE6C, and PDE6H, were analyzed based on data obtained from 7,195 probands with different eye conditions. A systematic genotype-phenotype analysis of these genes was performed based on these data, along with the data reported in the literature.

Results: Biallelic potential pathogenic variants (PPVs) in five of the six genes were identified in 119 probands with genetic eye diseases. The variants in CNGA3 were the most common and accounted for 81.5% (97/119). Of the 119 probands, 62.2% (74/119) have cone-rod dystrophy, whereas only 25.2% (30/119) have achromatopsia. No biallelic pathogenic variants in these genes were identified in patients with rod-dominant degeneration. A systematic review of genotypes and phenotypes revealed certain characteristics of each of the six genes, providing clues for the pathogenicity evaluation of the variants of the genes.

Conclusions: PPVs in the six genes were identified in various inherited retinal degeneration diseases, most of which are cone-dominant diseases but no rod-dominant diseases based on the data from a cohort of 7,195 probands with different eye conditions. The systematic genotype-phenotype analysis of these genes will be useful in drafting guidelines for the clinical genetic diagnostic application for the investigated genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases / genetics
  • Activating Transcription Factor 6 / genetics
  • Alleles
  • Cohort Studies
  • Color Vision Defects / congenital
  • Color Vision Defects / genetics*
  • Color Vision Defects / pathology
  • Cone-Rod Dystrophies / genetics*
  • Cyclic Nucleotide Phosphodiesterases, Type 6 / genetics
  • Cyclic Nucleotide-Gated Cation Channels / chemistry
  • Cyclic Nucleotide-Gated Cation Channels / genetics
  • DNA Mutational Analysis
  • Electroretinography
  • Exome Sequencing
  • Eye Proteins / genetics
  • Family
  • Genetic Association Studies
  • Genotype
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Humans
  • Mutation
  • Phenotype
  • Retinal Cone Photoreceptor Cells / pathology


  • ATF6 protein, human
  • Activating Transcription Factor 6
  • CNGA3 protein, human
  • CNGB3 protein, human
  • Cyclic Nucleotide-Gated Cation Channels
  • Eye Proteins
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • PDE6C protein, human
  • PDE6H protein, human
  • Heterotrimeric GTP-Binding Proteins