Genetic testing for retinal dystrophies and dysfunctions: benefits, dilemmas and solutions

Clin Exp Ophthalmol. 2007 Jul;35(5):473-85. doi: 10.1111/j.1442-9071.2007.01534.x.


Human retinal dystrophies have unparalleled genetic and clinical diversity and are currently linked to more than 185 genetic loci. Genotyping is a crucial exercise, as human gene-specific clinical trials to study photoreceptor rescue are on their way. Testing confirms the diagnosis at the molecular level and allows for a more precise prognosis of the possible future clinical evolution. As treatments are gene-specific and the 'window of opportunity' is time-sensitive; accurate, rapid and cost-effective genetic testing will play an ever-increasing crucial role. The gold standard is sequencing but is fraught with excessive costs, time, manpower issues and finding non-pathogenic variants. Therefore, no centre offers testing of all currently 132 known genes. Several new micro-array technologies have emerged recently, that offer rapid, cost-effective and accurate genotyping. The new disease chips from Asper Ophthalmics (for Stargardt dystrophy, Leber congenital amaurosis [LCA], Usher syndromes and retinitis pigmentosa) offer an excellent first pass opportunity. All known mutations are placed on the chip and in 4 h a patient's DNA is screened. Identification rates (identifying at least one disease-associated mutation) are currently approximately 70% (Stargardt), approximately 60-70% (LCA) and approximately 45% (Usher syndrome subtype 1). This may be combined with genotype-phenotype correlations that suggest the causal gene from the clinical appearance (e.g. preserved para-arteriolar retinal pigment epithelium suggests the involvement of the CRB1 gene in LCA). As approximately 50% of the retinal dystrophy genes still await discovery, these technologies will improve dramatically as additional novel mutations are added. Genetic testing will then become standard practice to complement the ophthalmic evaluation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Blindness / genetics
  • Calcium Channels, L-Type / genetics*
  • Carrier Proteins / genetics*
  • Child, Preschool
  • Color Vision Defects / genetics
  • Cyclic Nucleotide-Gated Cation Channels
  • DNA Mutational Analysis
  • Eye Proteins / genetics*
  • Genetic Testing*
  • Genotype
  • Guanylate Cyclase / genetics*
  • Humans
  • Infant
  • Ion Channels / genetics*
  • Male
  • Night Blindness / genetics
  • Pharmacogenetics
  • Receptors, Cell Surface / genetics*
  • Retinal Degeneration / diagnosis
  • Retinal Degeneration / genetics*
  • Retinal Degeneration / therapy
  • cis-trans-Isomerases


  • CACNA1F protein, human
  • CNGB3 protein, human
  • Calcium Channels, L-Type
  • Carrier Proteins
  • Cyclic Nucleotide-Gated Cation Channels
  • Eye Proteins
  • Ion Channels
  • Receptors, Cell Surface
  • guanylate cyclase 1
  • retinoid isomerohydrolase
  • Guanylate Cyclase
  • cis-trans-Isomerases