【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。(眼科,2020,29:180-186)更多还原

【Abstract】 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.(Ophthalmol CHN,2020,29:180-186)更多还原