目的:对3例CHARGE综合征患者进行基因变异检测，明确其可能的遗传学病因。方法:先证者及父母进行全外显子测序检测相关致病基因，对检出致病变异进行Sanger测序验证。结果:3例患儿均有程度不同的眼部病变，包括小眼球、小角膜、虹膜缺损、晶状体混浊、视神经视网膜脉络膜缺损等。测序结果示例1的n CHD7基因第2外显子存在c.1447delG(p.Val483Leufs*12)杂合移码变异；例2的n CHD7基因第36外显子存在c.7957C>T(p.Arg2653*)杂合无义变异；例3的n CHD7基因第2外显子存在c.1021_1048delAATCAGTCCGTACCAAGATACCCCAATG (p.Asn341Leufs*2)杂合移码变异，其中c.1447delG (p.Val4 83Leufs*12)和c.1021_1048delAATCAGTCCGTACCAAGATACCCCAATG(p.Asn341Leufs*2)变异未见报道，根据美国医学遗传学与基因组学学会遗传变异分类标准与指南，这两个均判定为致病性变异(PVS1＋PM2＋PM6)；c.7957C>T(p.Arg2653*)变异为已报道的可能致病性变异(PVS1＋PM2＋PP4)。Sanger测序结果验证例1和例3的变异为新发变异(n de novo)，例2的变异为可疑新发变异。n 结论:CHD7基因变异可能为3例CHARGE综合征患者的致病原因。n “,”Objective:To explore the genetic basis for three children patients with CHARGE syndrome.Methods:The three children and their parents were subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.Results:All patients had ocular anomalies including microphthalmia, microcornea, lens opacity, and coloboma of iris, optic nerve, retina and choroid. And all were found to carry heterozygous variants of the n CHD7 gene, which included two frameshifting variant, namely c. 1447delG (p.Val483Leufs*12) and c. 1021_1048delAATCAGTCCGTACCAAGATAC CCCAATG (p.Asn341Leufs*2) in exon 2, which were unreported previously and were pathogenic based on the American College of Medical Genetics and Genomics standards and guidelines(PVS1+ PM2+ PM6), and a nonsense variant c. 7957C>T (p.Arg2653*) in exon 36, which was known to be likely pathogenic(PVS1+ PM2+ PP4). Sanger sequencing confirmed that the two frameshifting mutations weren de novo, and the nonsense mutation was also suspected to be n de novo.n Conclusion:Pathological variants of the n CHD7 gene probably underlay the CHARGE syndrome in the three patients.n