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目的:观察分析Leber先天性黑矇（LCA）致病基因类型及临床表型特征。方法:回顾性临床研究。基因检测确诊的LCA患者6例及其家系成员18名纳入研究。患者分别来自6个无血缘关系家系。采集所有受检者外周静脉血，提取全基因组DNA。应用包含463个致病基因的遗传眼病捕获芯片进行靶向捕获富集高通量测序，对n TULP1、n RPGRIP1、n GUCY2D基因致病突变位点进行Sanger测序验证；通过相关数据库和PubMed文献检索基因变异的致病性，通过蛋白质预测软件阐释其功能。n 结果:6例患者中，男性3例，女性3例；年龄3~33岁。眼球震颤、指压眼征、畏光、夜盲5例；视网膜电图呈熄灭或近熄灭型3例；视网膜病变4例。基因检测结果显示，家系1、2、5患者分别存在n TULP1基因c.1318C> T （p.R440X）、c.1142T>G （p.V381G）复合杂合突变，c.1318C> T （p.R440X）纯合变异以及c.1153G> A （p.G385R）、c.1561C> T （p.P521S）复合杂合变异；家系3、6患者分别存在n RPGRIP1基因c.391delG （p.V131Sfs*39）、c.1468-2A> G （splicing）和c.715delA （p.K239Sfs*36）、c.1765C> T （p.Q589X）复合杂合变异；家系4患者存在n GUCY2D基因c.3177_3178delAC （p.R1060Rfs*11）纯合变异。父母均为相应杂合变异携带者。n TULP1基因c.1142T> G （p.V381G）、n RPGRIP1基因c.391delG （p.V131Sfs*39）、c.715delA （p.K239Sfs*36）及c.1765C> T （p.Q589X）和n GUCY2D基因c.3177_3178delAC （p.R1060Rfs*11）变异为致病性新变异。n TULP1基因产物蛋白381氨基酸位点在物种间具有高度保守性，蛋白质预测软件预测该变异为有害变异。n RPGRIP1基因c.391delG、c.715delA及c.1765C> T变异和n GUCY2D基因c.3177_3178delAC变异可导致各自的产物蛋白提前终止翻译，为致病性变异。n 结论:TULP1、n RPGRIP1、n GUCY2D基因的相关致病性变异分别导致了本研究6个家系不同患者罹患LCA 15型、LCA 6型或LCA 1型。n “,”Objective:To observe and analyze the pathogenic gene types and clinical phenotypes of Leber congenital amaurosis (LCA).Methods:A retrospective clinical study. Six patients with LCA confirmed by genetic testing and 18 family members were included in the study. The patients came from six unrelated families. The family was investigated with a specific hereditary eye disease enrichment panel which contained 463 known pathogenic genes and based on targeted exome capture technology first to indentify the potential pathogenic genes and mutations. Then the n TULP1 , n RPGRIP1 , n GUCY2D pathogenic mutations were conformed by Sanger sequencing. The pathogenicity of the gene variation was searched through relevant databases and PubMed literature, and its function was explained by protein prediction software.n Results:Of the 6 patients, 3 were males and 3 were females; the age was from 3 to 33 years. Nystagmus, finger pressing eyes, photophobia, and night blindness were seen in 5 cases; electroretinogram showed 3 cases of extinction or near extinction; and 4 cases of retinopathy. The results showed patients with compound heterozygous mutation of c.1318C> T and c.1142T> G, homozygous mutation ofc.1318C> T and compound heterozygous mutation of c.1153G> A and c.1561C> T ofn TULP1 in Family 1, Family 2 and Family 5, respectively. There were compound heterozygous mutations of n RPGRIP1 c.391delG and c.1468-2A> G in Family 3 and c.715delA and c.1765C> T in Family 6, respectively. Homozygous mutation of c.3177_3178delAC ofn GUCY2D was found in Family 4.The parents of all six patients were carriers of corresponding heterozygous mutations.n TULP1 gene c.1142T> G,n RPGRIP1 gene c.391delG, c.715delA and c.1765C> T andn GUCY2D gene c.3177_3178delAC mutations were novel mutations and unreported. The 381th amino acid locus of product protein of n TULP1 gene was highly conserved among species. The protein prediction software predicted that the mutation pathogenic. The c.391delG, c.715delA and c.1765C> T mutations ofn RPGRIP1 gene and c.3177_3178delAC mutation of n GUCY2D gene can lead to early translation termination of their product proteins, which are pathogenic variants.n Conclusion:The pathogenic mutations of n TULP1, n RPGRIP1 and n GUCY2D genes led to LCA 15, LCA 6 and LCA 1 in six families.n