title: Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor.
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 [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.
authors.affiliation: Department of Genetics, The Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: C L
authors.initials: CL
authors.lastname: Freund
authors.forename: C Y
authors.initials: CY
authors.lastname: Gregory-Evans
authors.forename: T
authors.initials: T
authors.lastname: Furukawa
authors.forename: M
authors.initials: M
authors.lastname: Papaioannou
authors.forename: J
authors.initials: J
authors.lastname: Looser
authors.forename: L
authors.initials: L
authors.lastname: Ploder
authors.forename: J
authors.initials: J
authors.lastname: Bellingham
authors.forename: D
authors.initials: D
authors.lastname: Ng
authors.forename: J A
authors.initials: JA
authors.lastname: Herbrick
authors.forename: A
authors.initials: A
authors.lastname: Duncan
authors.forename: S W
authors.initials: SW
authors.lastname: Scherer
authors.forename: L C
authors.initials: LC
authors.lastname: Tsui
authors.forename: A
authors.initials: A
authors.lastname: Loutradis-Anagnostou
authors.forename: S G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: C L
authors.initials: CL
authors.lastname: Cepko
authors.forename: S S
authors.initials: SS
authors.lastname: Bhattacharya
authors.forename: R R
authors.initials: RR
authors.lastname: McInnes
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D005799:Genes, Dominant / Q000235:genetics; D005801:Genes, Homeobox / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010375:Pedigree; D010786:Photoreceptor Cells / Q000502:physiology; D017354:Point Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012160:Retina / Q000737:chemistry; D012162:Retinal Degeneration / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; C109288:cone rod homeobox protein