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目的:对3例Menkes病患儿家系的n ATP7A基因进行变异分析，明确其致病原因，为临床诊断提供依据。n 方法:应用二代测序(next-generation sequencing，NGS)对3个Menkes病家系的先证者进行Menkes病相关致病基因n ATP7A基因外显子检测，发现可疑致病位点后，应用Sanger测序对家系成员和200名正常个体进行变异位点的验证分析，应用多重连接探针扩增技术(multiple ligation-dependent probe amplification，MLPA)对家系成员和20名正常个体进行基因缺失变异验证分析。n 结果:3例Menkes病患儿家系均检出n ATP7A基因变异，例1为c.1465A>T无义变异半合子，例2为c.3039_3043del移码变异半合子，均为未报道过的新变异，例3为第3～23外显子缺失变异半合子，文献已有报道。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，n ATP7A基因c.1465A>T变异和c.3039_3043del变异均判定为可能致病性变异(PVS1＋PM2)。n 结论:ATP7A基因的变异可能为这3例患儿的致病原因，基因检测结果为临床诊断提供了依据，新变异的检出丰富了Menkes病的基因变异谱。n “,”Objective:To explore the genetic basis for three children with Menkes disease.Methods:The patients were subjected to next-generation sequencing (NGS) to detect potential variants of the n ATP7A gene. Suspected variants were verified by Sanger sequencing of their family members and 200 healthy individuals. Multiplex ligation-dependent probe amplification (MLPA) was also carried out to detect potential deletions in their family members and 20 healthy individuals.n Results:Variants of the n ATP7A gene were detected in all of the three families, including a novel c. 1465A>T nonsense variant in family 1, a novel c. 3039_3043del frameshifting variant in family 2, and deletion of exons 3 to 23 in family 3, which was reported previously. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c. 1465A>T and c. 3039_3043del variants ofn ATP7A gene were predicted to be likely pathogenic(PVS1+ PM2).n Conclusion:Variants of the n ATP7A gene may underlay the Menkes disease in the three children. Above findings have facilitated clinical diagnosis and enriched the gene variant spectrum of Menkes disease.n