A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene

Am J Hum Genet. 1998 Nov;63(5):1307-15. doi: 10.1086/302101.


Mutations in the retinal-expressed gene CRX (cone-rod homeobox gene) have been associated with dominant cone-rod dystrophy and with de novo Leber congenital amaurosis. However, CRX is a transcription factor for several retinal genes, including the opsins and the gene for interphotoreceptor retinoid binding protein. Because loss of CRX function could alter the expression of a number of other retinal proteins, we screened for mutations in the CRX gene in probands with a range of degenerative retinal diseases. Of the 294 unrelated individuals screened, we identified four CRX mutations in families with clinical diagnoses of autosomal dominant cone-rod dystrophy, late-onset dominant retinitis pigmentosa, or dominant congenital Leber amaurosis (early-onset retinitis pigmentosa), and we identified four additional benign sequence variants. These findings imply that CRX mutations may be associated with a wide range of clinical phenotypes, including congenital retinal dystrophy (Leber) and progressive diseases such as cone-rod dystrophy or retinitis pigmentosa, with a wide range of onset.

Publication types

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

MeSH terms

  • Amino Acid Substitution
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 19*
  • Eye Proteins*
  • Female
  • Genetic Variation
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism*
  • Humans
  • Male
  • Molecular Sequence Data
  • Pedigree
  • Phenotype
  • Point Mutation*
  • Polymorphism, Single-Stranded Conformational
  • Retina / metabolism
  • Retinal Cone Photoreceptor Cells / metabolism
  • Retinal Diseases / genetics*
  • Retinal Rod Photoreceptor Cells / metabolism
  • Retinitis Pigmentosa / genetics*
  • Retinol-Binding Proteins / genetics
  • Rod Opsins / genetics
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism*


  • Eye Proteins
  • Homeodomain Proteins
  • Retinol-Binding Proteins
  • Rod Opsins
  • Trans-Activators
  • cone rod homeobox protein
  • interstitial retinol-binding protein

Associated data

  • GENBANK/AF024711