中国X连锁视网膜色素变性家系RPGR新突变  

Novel mutations of RPGR in Chinese families with X-linked retinitis pigmentosa

作　　者：闫博婧 郎需强 孙晓伟 杨丽萍[3] 李根林 Yan Bojing;Lang Xuqiang;Sun Xiaowei;Yang Liping;Li Genlin(Department of Opthalmology,Beijing Friendship Hospital,Capital Medical University.Beijing 100050,China;Department,of Ophthalmology,Yantai Yuhuangding Hospital A ffiliated to Medical College of Qingdao University,Yantai 264000,Shandong,China;Department of Ophthalmology,Peking University Third Hospital.Key Laboratory of Vision Loss and Restoration,Ministry of Education.Beijing 100191,China;Beijing Tongren Eye Center,Beijing Key Laboratory of Ophthalmology and Visual Science,Beijing Tongren Hospital,Capital Medical University,Beijing 100730,China)

机构地区：[1]首都医科大学附属北京友谊医院眼科,100050 [2]青岛大学附属烟台毓璜顶医院眼科,山东烟台264000 [3]北京大学第三医院眼科视觉损伤与修复教育部重点实验室,100191 [4]首都医科大学附属北京同仁医院,北京同仁眼科中心眼科学与视觉科学北京市重点实验室,100730

出　　处：《眼科》2020年第3期180-186,共7页Ophthalmology in China

基　　金：国家自然科学基金资助(81271046);首都医科大学2019年校自然培育基金(PYZ18115)。

摘　　要：目的检测分析被诊断为X连锁视网膜色素变性(XLRP)的三个中国家系内的基因突变.设计基因研究.研究对象三个中国XLRP家系共27位受试者(其中18人为男性).方法由同一医生收集家系成员的详细临床资料并进行眼部检查,采集三个家系的先证者及有条件采血者的外周静脉血,提取基因组DNA.应用PCR技术扩增RPGR和RP2基因的全部外显子和内含子交界区序列,包括RPGR基因15号外显子开放阅读框,产物直接测序进行突变分析.主要指标临床特征及基因测序结果.结果基因筛查证实了两个RPGR基因的新型无义突变(c.1541C>G;p.S514X和c.2833G>T;p.E945X)及一个错义突变(c.607G>C;p.A203P).基因型-表型的相关性分析表明家系3患者在接近ORF15下游位置存在突变,这种突变导致视锥细胞功能的早期丧失.ORF15无义突变的女性携带者临床表型重,呈现出部分显性遗传的特点.结论本研究证实了三种RPGR基因的新型突变,这一结果扩展了RPGR的突变谱及表型谱.Objective To identify genes and mutations in three Chinese families who presented with X-linked retinitis pigmentosa.Design Gene research.Participants 3 Chinese XLRP families including 27 participants(18 male).Methods The clinical data and ophthalmic examinations of three families were collected by the same doctor.Genomic DNA was extracted from peripheral blood.The coding regions and intron-exon boundaries of the retinitis pigmentosa GTPase regulator(RPGR)and RP2 genes,including the open reading frame 15(ORF15)of RPGR,were amplified by PCR and then sequenced directly.Main Outcome Measures Clinical characteristcs and gene sequencing.Results Mutation screening demonstrated two novel nonsense mutations(c.1541 C>G;p.S514 X and c.2833 G>T;p.E945 X)and one missense mutation(c.607 G>C;p.A203 P)in RPGR genes.Genotype-phenotype correlation analysis suggested that patients with mutation close to down-stream of ORF15 in family 3 manifested the early loss of cone function;female carries with ORF15 nonsense mutation showed heavier clinical manifestations.Thus,the inheritance patterns bias to dominant heredity.Conclusion We identified three novel mutations of RPGR genes,which broaden the spectrum of RPGR mutations and the phenotypic spectrum of the disease in Chinese family.

关 键 词：X连锁视网膜色素变性 DNA突变分析 家系 中国 

分 类 号：R774.1[医药卫生—眼科]