title: Whole-exome sequencing identifies OR2W3 mutation as a cause of autosomal dominant retinitis pigmentosa.
abstract: Retinitis pigmentosa (RP), a heterogeneous group of inherited ocular diseases, is a genetic condition that causes retinal degeneration and eventual vision loss. Though some genes have been identified to be associated with RP, still a large part of the clinical cases could not be explained. Here we reported a four-generation Chinese family with RP, during which 6 from 9 members of the second generation affected the disease. To identify the genetic defect in this family, whole-exome sequencing together with validation analysis by Sanger sequencing were performed to find possible pathogenic mutations. After a pipeline of database filtering, including public databases and in-house databases, a novel missense mutation, c. 424 C > T transition (p.R142W) in OR2W3 gene, was identified as a potentially causative mutation for autosomal dominant RP. The mutation co-segregated with the disease phenotype over four generations. This mutation was validated in another independent three-generation family. RT-PCR analysis also identified that OR2W3 gene was expressed in HESC-RPE cell line. The results will not only enhance our current understanding of the genetic basis of RP, but also provide helpful clues for designing future studies to further investigate genetic factors for familial RP.
authors.affiliation: Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Ma
authors.affiliation: BGI-Shenzhen, Shenzhen, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Guan
authors.affiliation: Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Epidemiology, Shanghai Cancer Institute, Shanghai, People's Republic of China.
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Jirong
authors.initials: J
authors.lastname: Long
authors.affiliation: Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Long
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: BGI-Shenzhen, Shenzhen, People's Republic of China.
authors.forename: Miaozhong
authors.initials: M
authors.lastname: Shen
authors.affiliation: BGI-Shenzhen, Shenzhen, People's Republic of China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen, People's Republic of China.
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen, People's Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yin
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, People's Republic of China [2] BGI-Tech, Shenzhen, People's Republic of China.
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Xu
authors.affiliation: BGI-Shenzhen, Shenzhen, People's Republic of China.
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Li
mesh_terms: D044466:Asian People / Q000235:genetics*; D002460:Cell Line; D002681:China; D030541:Databases, Genetic; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D018035:Receptors, Odorant / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA
chemical_list: C000601325:OR2W3 protein, human; D018035:Receptors, Odorant