Clinical and Molecular Characterization of Achromatopsia Patients: A Longitudinal Study

Int J Mol Sci. 2021 Feb 7;22(4):1681. doi: 10.3390/ijms22041681.


Achromatopsia (ACHM) is a rare genetic disorder of infantile onset affecting cone photoreceptors. To determine the extent of progressive retinal changes in achromatopsia, we performed a detailed longitudinal phenotyping and genetic characterization of an Italian cohort comprising 21 ACHM patients (17 unrelated families). Molecular genetic testing identified biallelic pathogenic mutations in known ACHM genes, including four novel variants. At baseline, the patients presented a reduced best corrected visual acuity (BCVA), reduced macular sensitivity (MS), normal dark-adapted electroretinogram (ERG) responses and undetectable or severely reduced light-adapted ERG. The longitudinal analysis of 16 patients (mean follow-up: 5.4 ± 1.0 years) showed a significant decline of BCVA (0.012 logMAR/year) and MS (-0.16 dB/year). Light-adapted and flicker ERG responses decreased below noise level in three and two patients, respectively. Only two patients (12.5%) progressed to a worst OCT grading during the follow-up. Our findings corroborate the notion that ACHM is a progressive disease in terms of BCVA, MS and ERG responses, and affects slowly the structural integrity of the retina. These observations can serve towards the development of guidelines for patient selection and intervention timing in forthcoming gene replacement therapies.

Keywords: CNGA3; CNGB3; GNAT2; Italian cohort; achromatopsia; cone photoreceptors.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers
  • Child, Preschool
  • Color Vision Defects / genetics*
  • Color Vision Defects / pathology*
  • Cyclic Nucleotide Phosphodiesterases, Type 6 / genetics
  • Cyclic Nucleotide-Gated Cation Channels / genetics
  • DNA Mutational Analysis
  • Eye Proteins / genetics
  • Female
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Humans
  • Longitudinal Studies
  • Male
  • Mutation*
  • Pedigree
  • Phenotype
  • Prognosis
  • Retrospective Studies
  • Tomography, Optical Coherence
  • Young Adult


  • Biomarkers
  • CNGA3 protein, human
  • CNGB3 protein, human
  • Cyclic Nucleotide-Gated Cation Channels
  • Eye Proteins
  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • PDE6C protein, human
  • Heterotrimeric GTP-Binding Proteins

Supplementary concepts

  • Achromatopsia 1