PUBLICATION
SPP2 Mutations Cause Autosomal Dominant Retinitis Pigmentosa
- Authors
- Liu, Y., Chen, X., Xu, Q., Gao, X., Tam, P.O., Zhao, K., Zhang, X., Chen, L.J., Jia, W., Zhao, Q., Vollrath, D., Pang, C.P., Zhao, C.
- ID
- ZDB-PUB-151016-13
- Date
- 2015
- Source
- Scientific Reports 5: 14867 (Journal)
- Registered Authors
- Zhao, Qingshun
- Keywords
- none
- MeSH Terms
-
- Adult
- Alleles
- Animals
- DNA Mutational Analysis
- Electroretinography
- Endoplasmic Reticulum/metabolism
- Gene Expression
- Genes, Dominant*
- Genetic Association Studies*
- HEK293 Cells
- Heterozygote
- Humans
- Male
- Middle Aged
- Mutation*
- Phenotype
- Phosphoproteins/chemistry
- Phosphoproteins/genetics*
- Phosphoproteins/metabolism
- Photoreceptor Cells/metabolism
- Protein Transport
- Retinitis Pigmentosa/diagnosis
- Retinitis Pigmentosa/genetics*
- Tomography, Optical Coherence
- Young Adult
- Zebrafish
- PubMed
- 26459573 Full text @ Sci. Rep.
Citation
Liu, Y., Chen, X., Xu, Q., Gao, X., Tam, P.O., Zhao, K., Zhang, X., Chen, L.J., Jia, W., Zhao, Q., Vollrath, D., Pang, C.P., Zhao, C. (2015) SPP2 Mutations Cause Autosomal Dominant Retinitis Pigmentosa. Scientific Reports. 5:14867.
Abstract
Retinitis pigmentosa (RP) shows progressive loss of photoreceptors involved with heterogeneous genetic background. Here, by exome sequencing and linkage analysis on a Chinese family with autosomal dominant RP, we identified a putative pathogenic variant, p.Gly97Arg, in the gene SPP2, of which expression was detected in multiple tissues including retina. The p.Gly97Arg was absent in 800 ethnically matched chromosomes and 1400 in-house exome dataset, and was located in the first of the two highly conserved disulfide bonded loop of secreted phosphoprotein 2 (Spp-24) encoded by SPP2. Overexpression of p.Gly97Arg and another signal peptide mutation, p.Gly29Asp, caused cellular retention of both endogenous wild type and exogenous mutants in vitro, and primarily affected rod photoreceptors in zebrafish mimicking cardinal feature of RP. Taken together, our data indicate that the two mutations of SPP2 have dominant negative effects and cellular accumulation of Spp-24 might be particularly toxic to photoreceptors and/or retinal pigment epithelium. SPP2 has a new role in retinal degeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping