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

Carol L. Freund, Cheryl Y. Gregory-Evans, Takahisa Furukawa, Myrto Papaioannou, Jens Looser, Lynda Ploder, James Bellingham, David Ng, Jo Anne S Herbrick, Alessandra Duncan, Stephen W. Scherer, Lap Chee Tsui, Aphrodite Loutradis-Anagnostou, Samuel G. Jacobson, Constance L. Cepko, Shomi S. Bhattacharya, Roderick R. McInnes

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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 [Δ1 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.
    Original languageEnglish
    Pages (from-to)543-553
    Number of pages10
    JournalCell
    Volume91
    Issue number4
    Publication statusPublished - 14 Nov 1997

    Keywords

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

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