| 제목 |
Usefullness of comprehensive next-generation sequencing panel for neuromuscular diseases in Korean |
| 소속 |
Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Department of Rehabilitation Medicine1, , National Traffic Injury Rehabilitation Hospital, College of Medicine, The Catholic University of Korea, Department of Rehabilitation Medicine2, Seoul St. Mary`s Hospital, College of Medicine, The Catholic University of Korea, Department of Rehabilitation Medicine3, Green Cross Genome, Department of Laboratory Medicine4 |
| 저자 |
Dae-Hyun Jang1*†, Dong-Woo Lee1, Hyun Mi Oh2, Jihye Park3, Ja-Hyun Jang4 |
Purpose: Neuromuscular disorder (NMD) is a very broad term that encompasses many diseases that affect the neuromuscular system. The genetic and clinical heterogeneity, unspecific clinical features, unidentified genes and the implication of large genes give challenges in routine molecular diagnosis, increasing turnaround time and effort to make molecular validation of the diagnosis. Recently, the targeted multi-gene panel sequencing (GPS) has been emerging as a molecular diagnostic tool, which is a part of next generation sequencing (NGS) technique. The multi-GPS generally ensures that all coding exons of the gene of interest are targeted, and all exons exhibit sufficiently high coverage, which is the most appropriate in diagnosing diseases like NMDs that are genetically heterogenous but similar in clinical aspect. There have been several multi-GPS studies of a specific NMD such like congenital myopathy, muscular dystrophy, motor neuron disease and polyneuropathy. However, few researches on the comprehensive NMDs gene panel have been conducted. Therefore, the purpose of the present study was to assess the usefulness of a comprehensive NMDs gene panel.
Methods: We designed two comprehensive NGS panels targeting 293 genes (version 1) and 410 genes (version 2) associated with NMDs. All patients were analyzed by a NGS panel (Version 1 was used from June 2016 to September 2017, and version 2 was used from October 2017 to May 2018), chromosomal microarray and karyotyping tests.
Results: Total 91 patients were enrolled and a genetic diagnosis was possible in 36 of 91 patients (39.5%). Thirty-four patients were diagnosed through the comprehensive NMDs gene panel, and two were confirmed by chromosome microarray test (Fig. 1). Approximately 38.5% (35/91) of the subjects using this panel version 1 and 2 were tested for myopathy as the initial impression, and 18 of 35 patients were diagnosed as myopathy and the diagnosis rate was as high as 50%. Neuropathy was suspected in 15 patients, of which 7 (46.7%) were diagnosed. In the case of ataxia, four of 12 patients (33.3%) were diagnosed. Spastic paraplegia was suspected in 20 patients, and 5 of them (25.0%) were diagnosed. A diagnostic yield of version 2 was higher than version 1 (14/39; 35.9% vs 20/52; 38.5%, Fig. 2). Total 37 definitive causative and 10 possible causative variants were identified, of which 17 were novel (Table 1).
Conclusions: Comprehensive NMDs gene panel can improve the genetic diagnosis efficiency. Due to the rapid discovery of disease causing genes, an update of gene panel is required.
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Figure 1. Flow chart of patients enrolled in this study
Figure 2. Diagnostic rate for each disease category using NGS panel version 1 and 2.
Table 1. Summary of 34 patients diagnosed with causative/possible causative variants using NGS panel.
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