Mutations in the gene PDE6C encoding the catalytic subunit of the cone photoreceptor phosphodiesterase in patients with achromatopsia

Hum Mutat. 2018 Oct;39(10):1366-1371. doi: 10.1002/humu.23606. Epub 2018 Aug 22.


Biallelic PDE6C mutations are a known cause for rod monochromacy, better known as autosomal recessive achromatopsia (ACHM), and early-onset cone photoreceptor dysfunction. PDE6C encodes the catalytic α'-subunit of the cone photoreceptor phosphodiesterase, thereby constituting an essential part of the phototransduction cascade. Here, we present the results of a study comprising 176 genetically preselected patients who remained unsolved after Sanger sequencing of the most frequent genes accounting for ACHM, and were subsequently screened for exonic and splice site variants in PDE6C applying a targeted next generation sequencing approach. We were able to identify potentially pathogenic biallelic variants in 15 index cases. The mutation spectrum comprises 18 different alleles, 15 of which are novel. Our study significantly contributes to the mutation spectrum of PDE6C and allows for a realistic estimate of the prevalence of PDE6C mutations in ACHM since our entire ACHM cohort comprises 1,074 independent families.

Keywords: PDE6C; achromatopsia; cone phosphodiesterase; mutation spectrum and prevalence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Catalytic Domain / genetics*
  • Child, Preschool
  • Color Vision Defects / diagnosis*
  • Color Vision Defects / genetics*
  • Computational Biology / methods
  • Cyclic Nucleotide Phosphodiesterases, Type 6 / chemistry
  • Cyclic Nucleotide Phosphodiesterases, Type 6 / genetics*
  • Databases, Genetic
  • Eye Proteins / chemistry
  • Eye Proteins / genetics*
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Mutation*
  • Phenotype
  • Retinal Cone Photoreceptor Cells / metabolism
  • Sequence Analysis, DNA


  • Eye Proteins
  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • PDE6C protein, human