title: A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene.
abstract: 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.
authors.affiliation: Human Genetics Center, School of Public Health, The University of Texas Health Science Center, Houston, TX 77225-0334, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Sohocki
authors.forename: L S
authors.initials: LS
authors.lastname: Sullivan
authors.forename: H A
authors.initials: HA
authors.lastname: Mintz-Hittner
authors.forename: D
authors.initials: D
authors.lastname: Birch
authors.forename: J R
authors.initials: JR
authors.lastname: Heckenlively
authors.forename: C L
authors.initials: CL
authors.lastname: Freund
authors.forename: R R
authors.initials: RR
authors.lastname: McInnes
authors.forename: S P
authors.initials: SP
authors.lastname: Daiger
mesh_terms: D019943:Amino Acid Substitution; D001483:Base Sequence; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D005136:Eye Proteins; D005260:Female; D014644:Genetic Variation; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012160:Retina / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism; D012164:Retinal Diseases / Q000235:genetics*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000235:genetics*; D012177:Retinol-Binding Proteins / Q000235:genetics; D017299:Rod Opsins / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D012177:Retinol-Binding Proteins; D017299:Rod Opsins; D015534:Trans-Activators; D000099214:Retinol-Binding Proteins, Interstitial; C109288:cone rod homeobox protein