PUBLICATION
A Mutation in ZNF513, a Putative Regulator of Photoreceptor Development, Causes Autosomal-Recessive Retinitis Pigmentosa
- Authors
- Li, L., Nakaya, N., Chavali, V.R., Ma, Z., Jiao, X., Sieving, P.A., Riazuddin, S., Tomarev, S.I., Ayyagari, R., Riazuddin, S.A., and Hejtmancik, J.F.
- ID
- ZDB-PUB-100830-5
- Date
- 2010
- Source
- American journal of human genetics 87(3): 400-409 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Eye Proteins/chemistry
- Eye Proteins/genetics*
- Transcription Factors/chemistry
- Transcription Factors/genetics*
- Gene Expression Regulation, Developmental
- Protein Binding
- Chlorocebus aethiops
- Photoreceptor Cells, Vertebrate/metabolism*
- Photoreceptor Cells, Vertebrate/pathology
- Female
- Mice
- Male
- Mutation/genetics*
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/genetics*
- COS Cells
- Pedigree
- DNA Mutational Analysis
- Retinitis Pigmentosa/genetics*
- Humans
- Mutant Proteins/metabolism
- Retinal Cone Photoreceptor Cells/pathology
- Chromatin/metabolism
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Retinal Rod Photoreceptor Cells/pathology
- Amino Acid Sequence
- Genetic Markers
- Lod Score
- Chromosome Mapping
- Genes, Recessive/genetics*
- Molecular Sequence Data
- Animals
- Zebrafish/embryology
- PubMed
- 20797688 Full text @ Am. J. Hum. Genet.
Citation
Li, L., Nakaya, N., Chavali, V.R., Ma, Z., Jiao, X., Sieving, P.A., Riazuddin, S., Tomarev, S.I., Ayyagari, R., Riazuddin, S.A., and Hejtmancik, J.F. (2010) A Mutation in ZNF513, a Putative Regulator of Photoreceptor Development, Causes Autosomal-Recessive Retinitis Pigmentosa. American journal of human genetics. 87(3):400-409.
Abstract
Retinitis pigmentosa (RP) is a phenotypically and genetically heterogeneous group of inherited retinal degenerations characterized clinically by night blindness, progressive constriction of the visual fields, and loss of vision, and pathologically by progressive loss of rod and then cone photoreceptors. Autosomal-recessive RP (arRP) in a consanguineous Pakistani family previously linked to chromosome 2p22.3-p24.1 is shown to result from a homozygous missense mutation (c.1015T>C [p.C339R]) in ZNF513, encoding a presumptive transcription factor. znf513 is expressed in the retina, especially in the outer nuclear layer, inner nuclear layer, and photoreceptors. Knockdown of znf513 in zebrafish reduces eye size, retinal thickness, and expression of rod and cone opsins and causes specific loss of photoreceptors. These effects are rescued by coinjection with wild-type (WT) but not p.C339R-znf513 mRNA. Both normal and p.C339R mutant ZNF513 proteins expressed in COS-7 cells localize to the nucleus. ChIP analysis shows that only the wild-type but not the mutant ZNF513 binds to the Pax6, Sp4, Arr3, Irbp, and photoreceptor opsin promoters. These results suggest that the ZNF513 p.C339R mutation is responsible for RP in this family and that ZNF513 plays a key role in the regulation of photoreceptor-specific genes in retinal development and photoreceptor maintenance.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping