PUBLICATION
A mutation in ADIPOR1 causes nonsyndromic autosomal dominant retinitis pigmentosa
- Authors
- Zhang, J., Wang, C., Shen, Y., Chen, N., Wang, L., Liang, L., Guo, T., Yin, X., Ma, Z., Zhang, B., Yang, L.
- ID
- ZDB-PUB-160923-10
- Date
- 2016
- Source
- Human genetics 135(12): 1375-1387 (Journal)
- Registered Authors
- Shen, Yan, Zhang, Bo
- Keywords
- none
- MeSH Terms
-
- RNA, Messenger/genetics
- Exome/genetics
- Humans
- Pedigree
- Zebrafish/genetics
- Receptors, Adiponectin/genetics*
- Exons/genetics
- Gene Knockdown Techniques
- Asian People
- Animals
- Male
- Mutation
- Female
- Phenotype
- Genetic Predisposition to Disease*
- Retinitis Pigmentosa/genetics*
- Retinitis Pigmentosa/pathology
- Amino Acid Substitution/genetics
- PubMed
- 27655171 Full text @ Hum. Genet.
Citation
Zhang, J., Wang, C., Shen, Y., Chen, N., Wang, L., Liang, L., Guo, T., Yin, X., Ma, Z., Zhang, B., Yang, L. (2016) A mutation in ADIPOR1 causes nonsyndromic autosomal dominant retinitis pigmentosa. Human genetics. 135(12):1375-1387.
Abstract
Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous disorder characterized by night blindness, visual field constriction, and severely reduced visual acuity. Despite a number of genes being implicated in RP pathogenesis, the genetic etiology of the disease remains unknown in many patients. In this study, our aim was to identify the disease-causing mutation of a large Chinese family with autosomal dominant RP (adRP). Targeted exon capture sequencing was initially performed to screen mutations in known disease-causing genes, followed by exome sequencing. In doing so, a heterozygous mutation in ADIPOR1 (c.929A > G) that results in an amino acid substitution (p.Y310C) was identified to co-segregate with the disease phenotype in this family. Adipor1 is wildly expressed throughout the body, but appears to be enriched in the photoreceptor inner and outer segments. The p.Y310C mutation, predicted to affect the structure and function of the protein, was confirmed to affect protein folding and its subcellular localization in vitro. In addition, knockdown of adipor1 expression in a zebrafish model with morpholino (MO) preferentially reduced the number of rod photoreceptors, with no effect on the number of cones, a phenotype that is characteristic of RP. Furthermore, the knockdown phenotype was partially rescued by injecting wild-type, but not mutant, human ADIPOR1 mRNA. We conclude that ADIPOR1 is a novel adRP-causing gene and plays an important role in rod development and maintenance.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping