中文摘要：

目的研究一例疑是视网膜变性的患儿,进行基因检测并作出明确的基因诊断。方法常规检查患儿和家属的眼睛,特别是视网膜的情况。收集患者及家庭成员的外周静脉血液,提取基因组DNA。通过目标区域外显子组序列捕获联合新一代测序（简称目标区域测序）,利用生物信息学分析筛选出一系列可能的突变,再通过Sanger测序和共分离研究进行验证,从而确定先证者的致病突变。最后,通过PCR和Sanger测序检测突变基因。结果患儿视力障碍严重,眼底检查所见符合视网膜变性。其他人眼睛正常。基因诊断结果表明,先证者携带CRB1基因的复合杂合性致病突变（c.3521G〉C和c.1141_1142 ins TGGCT）。这两个突变分别来源于父亲（c.3521G〉C,p.C1174S）和母亲（c.1141_1142ins TGGCT）,为隐性遗传。患儿的弟弟（新生儿）只有一个c.1141_1142ins TGGCT突变,表明他不会发病。建议新生儿长大后在生育前要进行遗传检查和咨询。结论目标区域测序的基因诊断方法是检测视网膜变性疾病突变基因的强大工具,有利于对患者做出早期、明确、分子水平的诊断,在特定疾病的理解、预防和预后判定方面能发挥重要作用。同时为其尚无法做临床检查和诊断的新生儿弟弟进行了基因诊断,通过预测,排除了发病的可能。

英文摘要：

Objective To investigate genetic diagnosis of CRB1 mutations in retinal degeneration by target exon sequencing. Methods A 3-year child with suspected Leber＇s congenital amaurosis（ LCA）and 3 family members were included in the study. Peripheral vein blood was collected and genome DNA was extracted; the target exon capture and next generation sequencing（ Candidate Exon Sequencing） was performed. Sanger sequencing validation and family cosegregation study were used to identify the causative mutation based on bioinformatic analysis. Results Compound heterozygote mutations of CRB1 gene,c. 3521 G C and c. 1141_1142 ins TGGCT,were identified in the proband.The gene mutations（ c. 3521 G C,p. C1174S） and（ c. 1141_1142ins TGGCT） were detected from the father and mother of the proband,respectively; while only one mutation（ c. 1141_1142 ins TGGCT）was detected in proband＇s younger brother. Conclusion Target exon sequencing can be used to screen known causative gene for retinal degenerative diseases.