A frameshift insertion in the cone cyclic nucleotide gated cation channel causes complete achromatopsia in a consanguineous family from a rural isolate

Eur J Hum Genet. 2002 Oct;10(10):638-42. doi: 10.1038/sj.ejhg.5200856.


Complete achromatopsia is genetically heterogeneous and segregates with mutations in CNGA3 or CNGB3 genes, which respectively encode for alpha- and beta-subunits of the cyclic-nucleotide-gated (CNG) cation channel expressed in cone photoreceptors. High incidence of the disease (1 in 60) was detected in a rural isolate in central Chile. We excluded previously reported mutations in a consanguineous kindred with five affected members. Genotype analysis with short tandem repeat polymorphic (STRP) markers provided evidence to search for the causative mutation in CNGB3. Two sequence variations, c.492_493insT and c.488A>G, flanking an adenosine (A(5)) repeat in exon 4 were identified. The frameshift mutation creates two consecutive stop codons in exon 5 that would induce premature translation termination. The severely truncated beta-subunit is likely to render a nonfunctional cone CNG channel and cause total colour blindness in this kindred.

MeSH terms

  • Chromosomes, Human, Pair 8
  • Color Vision Defects / genetics*
  • Cyclic Nucleotide-Gated Cation Channels
  • Female
  • Frameshift Mutation*
  • Humans
  • Ion Channels / genetics*
  • Ion Channels / metabolism
  • Male
  • Pedigree
  • Retinal Cone Photoreceptor Cells / metabolism*


  • Cyclic Nucleotide-Gated Cation Channels
  • Ion Channels