Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor

Cell. 1997 Nov 14;91(4):543-53. doi: 10.1016/s0092-8674(00)80440-7.


Genes associated with inherited retinal degeneration have been found to encode proteins required for phototransduction, metabolism, or structural support of photoreceptors. Here we show that mutations in a novel photoreceptor-specific homeodomain transcription factor gene (CRX) cause an autosomal dominant form of cone-rod dystrophy (adCRD) at the CORD2 locus on chromosome 19q13. In affected members of a CORD2-linked family, the highly conserved glutamic acid at the first position of the recognition helix is replaced by alanine (E80A). In another CRD family, a 1 bp deletion (E168 [delta1 bp]) within a novel sequence, the WSP motif, predicts truncation of the C-terminal 132 residues of CRX. Mutations in the CRX gene cause adCRD either by haploinsufficiency or by a dominant negative effect and demonstrate that CRX is essential for the maintenance of mammalian photoreceptors.

Publication types

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

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 19 / genetics
  • Conserved Sequence / genetics
  • Female
  • Frameshift Mutation / genetics*
  • Genes, Dominant / genetics
  • Genes, Homeobox / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Molecular Sequence Data
  • Organ Specificity
  • Pedigree
  • Photoreceptor Cells / physiology
  • Point Mutation / genetics*
  • RNA, Messenger / analysis
  • Retina / chemistry
  • Retinal Degeneration / genetics*
  • Sequence Homology, Amino Acid
  • Trans-Activators / genetics*
  • Transcription Factors / genetics


  • Homeodomain Proteins
  • RNA, Messenger
  • Trans-Activators
  • Transcription Factors
  • cone rod homeobox protein

Associated data

  • GENBANK/AF024711