Retinal degenerations with truncation mutations in the cone-rod homeobox (CRX) gene

Invest Ophthalmol Vis Sci. 1998 Nov;39(12):2417-26.


Purpose: To define the phenotypes of retinal degenerations associated with mutations in the gene encoding CRX (cone-rod homeobox), a photoreceptor-specific transcription factor.

Methods: Heterozygotes with the E168 [delta1 bp], E168 [delta2 bp], or G217 [delta1 bp] CRXgene mutation were studied clinically, with visual function tests, including rod and cone perimetry and electroretinography (ERG), and with optical coherence tomography (OCT).

Results: Clinical diagnoses included autosomal dominant cone-rod dystrophy in one family (E168 [delta1 bp] mutation) and simplex Leber congenital amaurosis in two families (E168 [delta2 bp], G217 [delta1 bp] mutations). In the family with the E168 [delta1 bp] mutation, two siblings had relatively mild disease expression in the third decade of life. The central retinas of these two patients had profound loss of rod and short wavelength cone function; long/middle wavelength cone thresholds were elevated at fixation, but there were greater paracentral than central abnormalities. Peripheral retinal dysfunction was evident by psychophysics and by maximum amplitude loss for rod- and cone-isolated ERG photoreceptor responses. OCT cross-sectional reflectance images showed decreased central retinal thickness consistent with photoreceptor loss. An additional member of this family (E168 [delta1 bp] mutation) and two other patients (representing E168 [delta2 bp] and G217 [delta1 bp] mutations) had a severe phenotype with retina-wide loss of function and islands of function remaining only in the temporal periphery.

Conclusions: Truncation mutations in CRX are associated with retinopathies that share phenotypic features but vary in disease severity. The disease mechanism could involve abnormal photoreceptor development compounded by a disturbance in the maintenance of photoreceptors in the mature retina.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Child
  • Electroretinography
  • Female
  • Homeodomain Proteins / genetics*
  • Humans
  • Middle Aged
  • Mutation*
  • Pedigree
  • Phenotype
  • Photoreceptor Cells, Vertebrate / physiology*
  • Psychophysics
  • Retinal Degeneration / genetics*
  • Retinal Degeneration / physiopathology
  • Tomography
  • Trans-Activators / genetics*
  • Visual Acuity
  • Visual Field Tests
  • Visual Fields


  • Homeodomain Proteins
  • Trans-Activators
  • cone rod homeobox protein