摘要目的:评估拷贝数变异测序（CNV-seq）技术对假肥大型肌营养不良［包括迪谢内肌营养不良（DMD）和贝克肌营养不良（BMD）］患者 DMD基因缺失/重复的检测价值。 方法:收集于2018年4月至2023年11月就诊于昆明理工大学附属医院/云南省第一人民医院医学遗传科，并以多重连接依赖性探针扩增（MLPA）技术完成了 DMD基因缺失/重复检测的177例患者。其中包括MLPA检测结果正常的阴性对照90例以及携带 DMD基因缺失/重复的87例患者（61例DMD和26例BMD）。单盲法采用CNV-seq技术对受试者 DMD基因缺失/重复进行检测，对比CNV-seq和MLPA的检出结果，获得CNV-seq对患者 DMD基因缺失/重复的检出效能。 结果:相较于“金标准”技术MLPA，CNV-seq对患者 DMD基因缺失/重复的检出总符合率为88.7%（157/177），敏感度为77.0%（67/87），特异度和阳性预测值均为100.0%（分别为90/90和67/67），阴性预测值为81.8%（90/110），Kappa值为0.773（ P<0.001）。在87例阳性患者中，CNV-seq共检出 DMD基因缺失/重复患者67例（77.0%），其中62例为缺失变异，5例为重复变异，片段长度范围为150~750 kb。CNV-seq漏检了23.0%（20/87）的阳性患者，MLPA结果显示 DMD基因均存在1~4个外显子缺失/重复，涉及片段大小均<50 kb，低于CNV-seq技术的检测分辨率（100 kb）。CNV-seq对BMD的检出率（84.6%，22/26）高于DMD（73.8%，45/61），但两者间的差异并无统计学意义（ χ2=1.211， P=0.271）。阴性对照组中CNV-seq与MLPA结果一致，均为阴性。 结论:CNV-seq能检出77.0%（67/87）的DMD/BMD患者 DMD基因致病性缺失/重复，但对于片段长度<100 kb的缺失/重复则全部漏检，故推荐其在介入性产前诊断等常规应用场景中作为不增加成本的机会性筛查技术使用。

abstractsObjective:To validate the usefulness of copy number variation sequencing (CNV-seq) in detecting the deletion/duplication of the DMD gene in Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) patients. Methods:One hundred and seventy-seven cases who visited the Department of Medical Genetics, Affiliated Hospital of Kunming University of Science and Technology/the First People′s Hospital of Yunnan Province from April 2018 to November 2023 were collected. All patients had previously accepted multiplex ligation-dependent probe amplification (MLPA) to detect the deletion/duplication of the DMD gene, including 90 cases of normal control with a negative result of MLPA and 87 cases with the deletion or duplication of the DMD gene (61 cases of DMD and 26 cases of BMD). CNV-seq was performed in a single-blind manner to detect DMD gene deletion or duplication for all of 177 cases to obtain the detection efficiency of CNV-seq in comparison with MLPA. Results:Comparing to MLPA, CNV-seq had a coincidence rate of 88.7% (157/177) for detecting DMD gene deletion/duplication, with a sensitivity of 77.0% (67/87), a specificity and a positive predictive value of both 100.0% (90/90 and 67/67, respectively), a negative predictive value of 81.8% (90/110), and a Kappa value of 0.773. Of the 87 patients with the deletion or duplication of the DMD gene, CNV-seq detected 67 cases with DMD gene deletion/duplication, including 62 cases with deletion and 5 cases with duplication, with fragment ranging from 150 to 750 kb. While CNV-seq missed 23.0% (20/87) of positive cases, mainly due to the involved fragments spanning only 1 to 4 exons, and with a variation size less than 50 kb, below the resolution (100 kb) of CNV-seq. The detection rate of CNV-seq in BMD cases (84.6%, 22/26) was a little higher than that in DMD cases (73.8%, 45/61), but there was no significant difference between 2 subgroups ( χ2=1.211, P=0.271). The results of CNV-seq in normal controls were all negative, and consistent with the results of MLPA. Conclusion:CNV-seq can detect 77.0% (67/87) of deletion/duplication of the DMD gene in patients with DMD/BMD, while the deletion/duplication less than 100 kb may be inevitably unidentified, therefore it is recommended as an assistant screening technique in prenatal diagnosis for DMD gene deletion or duplication.