title: Novel compound heterozygous mutation in the CNGA1 gene underlie autosomal recessive retinitis pigmentosa in a Chinese family.
abstract: Retinitis pigmentosa (RP) describes a group of inherited retinopathies that are characterized by the progressive degeneration of photoreceptor neurons, which causes night blindness, a reduction in the peripheral visual field and decreased visual acuity. More than 50 RP-related genes have been identified. In the present study, we analysed a Chinese family with autosomal recessive RP. We identified a compound heterozygous mutation, c.265delC and c.1537G>A, in CNGA1 using targeted next-generation sequencing (NGS) of RP-causing genes. The mutations were validated in the family members by Sanger sequencing. The mutations co-segregated with the RP phenotype and were absent from ethnically-matched control chromosomes. The mutant (mut) CNGA1 p.(G513R) protein caused by the mis-sense novel mutation c.1537G>A was expressed in vitro. The mut CNGA1 p.(G513R) protein was largely retained inside the cell rather than being targeted to the plasma membrane, suggesting the absence of cGMP-gated cation channels in the plasma membrane would be deleterious to rod photoreceptors, leading lead to RP.
authors.affiliation: Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing 400038, China Department of Ophthalmology, General Hospital of Chinese PLA, Beijing 100853, China Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing 400038, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing 400038, China Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing 400038, China.
authors.forename: Ling-Hui
authors.initials: LH
authors.lastname: Qu
authors.affiliation: Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing 400038, China Department of Ophthalmology, General Hospital of Chinese PLA, Beijing 100853, China Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing 400038, China.
authors.forename: Bao-Ke
authors.initials: BK
authors.lastname: Hou
authors.affiliation: Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing 400038, China Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing 400038, China.
authors.forename: Hai-Wei
authors.initials: HW
authors.lastname: Xu
authors.affiliation: Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing 400038, China Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing 400038, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Meng
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China zhengqinyin253@126.com chipuipang@163.com.
authors.forename: Chi-Pui
authors.initials: CP
authors.lastname: Pang
authors.affiliation: Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing 400038, China Department of Ophthalmology, General Hospital of Chinese PLA, Beijing 100853, China Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing 400038, China zhengqinyin253@126.com chipuipang@163.com.
authors.forename: Zheng-Qin
authors.initials: ZQ
authors.lastname: Yin
mesh_terms: D019943:Amino Acid Substitution; D044466:Asian People; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics*; D005190:Family; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D012174:Retinitis Pigmentosa / Q000235:genetics*
chemical_list: C518243:CNGA1 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels
keywords: CNGA1; mutation; next-generation sequencing; retinitis pigmentosa