title: A mutation in ADIPOR1 causes nonsyndromic autosomal dominant retinitis pigmentosa.
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.
authors.affiliation: Key Laboratory of Vision Loss and Restoration, Department of Ophthalmology, Ministry of Education, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Jinlu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Vision Loss and Restoration, Department of Ophthalmology, Ministry of Education, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Changguan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, School of Life Sciences, Peking University, Beijing, 100871, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Key Laboratory of Vision Loss and Restoration, Department of Ophthalmology, Ministry of Education, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Chen
authors.affiliation: Beijing Key Laboratory of Tumor Systems Biology, Department of Pathology, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Likun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Tumor Systems Biology, Department of Pathology, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liang
authors.affiliation: Key Laboratory of Vision Loss and Restoration, Department of Ophthalmology, Ministry of Education, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Tong
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China.
authors.forename: Xiaobei
authors.initials: X
authors.lastname: Yin
authors.affiliation: Key Laboratory of Vision Loss and Restoration, Department of Ophthalmology, Ministry of Education, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, School of Life Sciences, Peking University, Beijing, 100871, People's Republic of China. bzhang@pku.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Vision Loss and Restoration, Department of Ophthalmology, Ministry of Education, Peking University Third Hospital, Beijing, People's Republic of China. alexlipingyang@bjmu.edu.cn.
authors.forename: Liping
authors.identifier: 0000-0002-4239-228X
authors.initials: L
authors.lastname: Yang
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D044466:Asian People; D059472:Exome / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D055785:Gene Knockdown Techniques; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D054419:Receptors, Adiponectin / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology; D015027:Zebrafish / Q000235:genetics
chemical_list: C475418:ADIPOR1 protein, human; D012333:RNA, Messenger; D054419:Receptors, Adiponectin