Mutations in the Cone-Rod Homeobox Gene Are Associated with the Cone-Rod Dystrophy Photoreceptor Degeneration
| Autor: | Gerald A. Fishman, Donald J. Zack, Prabodha K. Swain, Qing Liang Wang, Kevin D. Brady, Edwin M. Stone, Anand Swaroop, Shiming Chen, Paul A. Sieving, Louisa M. Affatigato, Caraline L. Coats, Samuel G. Jacobson |
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| Rok vydání: | 1997 |
| Předmět: |
Proband
Adult Male Recombinant Fusion Proteins Neuroscience(all) Molecular Sequence Data Visual Acuity Locus (genetics) Biology Polymerase Chain Reaction Retina Pinealocyte law.invention 03 medical and health sciences 0302 clinical medicine law Humans Point Mutation Codon Gene 030304 developmental biology Genes Dominant Sequence Deletion Genetics Homeodomain Proteins 0303 health sciences Base Sequence General Neuroscience Dystrophy Chromosome Mapping Exons Middle Aged Molecular biology Photoreceptor degeneration Introns Pedigree DNA-Binding Proteins 030221 ophthalmology & optometry Recombinant DNA Trans-Activators Homeobox Female sense organs Lod Score Chromosomes Human Pair 19 Retinitis Pigmentosa |
| Zdroj: | Neuron. 19(6):1329-1336 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/s0896-6273(00)80423-7 |
| Popis: | Crx is a novel paired-like homeodomain protein that is expressed predominantly in retinal photoreceptors and pinealocytes. Its gene has been mapped to chromosome 19q13.3, the site of a disease locus for autosomal dominant cone-rod dystrophy (CORDII). Analysis of the proband from a family with autosomal dominant CORD revealed an Arg41Trp substitution in the third residue of the CRX homeodomain. The sequence change cosegregated with the disease phenotype and was not detected in 247 normal controls. Recombinant CRX homeodomain containing the Arg41Trp substitution showed decreased DNA binding activity. Analysis of another 169 CORD probands identified three additional CRX sequence variations (Arg41Gln, Val242Met, and a 4 bp deletion in codons 196/7) that were not found among the controls. This data suggests that mutations in the CRX gene are associated with photoreceptor degeneration and that the Crx protein is necessary for the maintenance of normal cone and rod function. |
| Databáze: | OpenAIRE |
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