目的:通过临床表型分析、n NHS基因变异检测明确1个Nance-Horan综合征家系的致病原因，为临床诊断提供依据。n 方法:提取先证者及其母亲、外祖父母外周血基因组DNA，进行先天性白内障相关基因的高通量技术测序。根据美国医学遗传学与基因组学学会( American College of Medical Genetics and Genomics ，ACMG)遗传变异分类标准与指南判断变异位点的致病性，并进行Sanger测序验证。提取先证者母亲mRNA，用逆转录-PCR检测其转录水平的表达；用短串联重复序列分析其亲缘关系。结果:先天性白内障相关基因检测结果显示先证者n NHS基因存在c.766dupC(p.Leu256Profs*21)半合子变异，母亲n NHS基因存在c.766dupC杂合变异，表型正常的外祖父母及100名表型正常的对照中均未检测到该变异，HGMD等数据库未见该变异的报道。根据ACMG遗传变异分类标准与指南，n NHS基因c.766dupC(p.Leu256Profs*21)变异被判定为致病性变异(PVS1+PM2+PM6+PP4)。n 结论:c．766dupC变异可能为该Nance-Horan综合征家系的致病原因。“,”Objective:To explore the genetic basis for a pedigree affected with Nance-Horan syndrome.Methods:Clinical manifestation of the patients was analyzed. Genomic DNA was extracted from peripheral blood samples of the pedigree members and 100 unrelated healthy controls. A panel of genes for congenital cataract was subjected to next-generation sequencing (NGS), and candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of American College of Medical Genetics and Genomics (ACMG). mRNA expression was determined by reverse transcriptase-PCR (RT-PCR). Linkage analysis based on short tandem repeats was carried out to confirm the consanguinity.Results:A small insertional variant c. 766dupC(p.Leu256Profs*21) of the n NHS gene was identified in the proband and his affected mother, but not among unaffected members and the 100 healthy controls. The variant was unreported in Human Gene Mutation Database (HGMD) and other databases. Based on the ACMG guideline, the variant is predicted to be pathogenic (PVS1+ PM2+ PM6+ PP4).n Conclusion:The novel variant c. 766dupC of the n NHS gene probably underlay the X-linked dominant Nance-Horan syndrome in this pedigree.n