title: Identification of a rhodopsin gene mutation in a large family with autosomal dominant retinitis pigmentosa.
abstract: Retinitis pigmentosa (RP) is a genetically highly heterogeneous retinal disease and one of the leading causes of blindness in the world. Next-generation sequencing technology has enormous potential for determining the genetic etiology of RP. We sought to identify the underlying genetic defect in a 35-year-old male from an autosomal-dominant RP family with 14 affected individuals. By capturing next-generation sequencing (CNGS) of 144 genes associated with retinal diseases, we identified eight novel DNA variants; however, none of them cosegregated for all the members of the family. Further analysis of the CNGS data led to identification of a recurrent missense mutation (c.403C > T, p.R135W) in the rhodopsin (RHO) gene, which cosegregated with all affected individuals in the family and was not observed in any of the unaffected family members. The p.R135W mutation has a reference single nucleotide polymorphism (SNP) ID (rs104893775), and it appears to be responsible for the disease in this large family. This study highlights the importance of examining NGS data with reference SNP IDs. Thus, our study is important for data analysis of NGS-based clinical genetic diagnoses.
authors.affiliation: School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
authors.forename: Xinping
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology, Beijing Children's Hospital, Capital Medical University, Beijing 100045 China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Zhejiang Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035 China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
authors.forename: Ding
authors.initials: D
authors.lastname: Chen
authors.affiliation: School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
authors.forename: Xuting
authors.initials: X
authors.lastname: Hu
authors.affiliation: School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
authors.forename: Jinling
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou, Zhengzhou University, Henan 450052 China.
authors.forename: Limin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000 China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Wu
authors.affiliation: School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.affiliation: School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005799:Genes, Dominant; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000235:genetics*; D012243:Rhodopsin / Q000737:chemistry / Q000235:genetics*
chemical_list: D012243:Rhodopsin