Usefulness of copy number variation sequencing in detecting deletion/duplication of the DMD gene in Duchenne/Becker muscular dystrophy patients
10.3760/cma.j.cn113694-20240813-00552
- VernacularTitle:采用拷贝数变异测序技术对假肥大型肌营养不良患者 DMD基因缺失/重复的检测价值研究
- Author:
Xia QIU
1
;
Jingjing GUO
1
;
Chanchan JIN
1
;
Jing HE
1
;
Lei WANG
1
;
Bicheng YANG
1
;
Yinhong ZHANG
1
;
Baosheng ZHU
1
;
Xinhua TANG
1
Author Information
1. 昆明理工大学附属医院/云南省第一人民医院医学遗传科 国家卫生健康委西部优生与出生缺陷防控重点实验室 云南省出生缺陷与遗传病研究重点实验室，昆明 650032
- Publication Type:Journal Article
- Keywords:
Muscular dystrophies;
Diagnostic techniques, neurological;
DMD gene;
Multiplex ligation-dependent probe amplification;
Copy number variation sequenci
- From:
Chinese Journal of Neurology
2025;58(2):138-146
- CountryChina
- Language:Chinese
-
Abstract:
Objective: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.
